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Will 2024 Be Easier on the Eyes?
The burdens that monthly or every-other-month injections in the eye impose on patients with retinal diseases are well-known to be barriers to care for many people with these conditions. Making treatment less onerous has driven research into new treatments since the US Food and Drug Administration (FDA) approved ranibizumab (Lucentis) in 2006 as the first anti–vascular endothelial growth factor (VEGF) for the treatment of age-related macular degeneration (AMD) and other retinal diseases.
Those Several of those investigational therapies are poised to hit meaningful milestones in 2024.
Regular Eye Injections: How We Got Here
Ranibizumab originally received approval as a monthly injection. Since then, protocols have evolved to space those injections out to every other month in some, but not all, patients.
New drugs have emerged that require less frequent injections. In 2022, the anti-VEGF and angiopoietin-2 inhibitor faricimab (Vabysmo) was approved for dosing up to every 4 months. Last year, the FDA approved a high-dose formulation of the anti-VEGF treatment aflibercept 8 mg (Eylea HD) to be given every 2-4 months, as well.
But even these treatments require patients going to the office at least three or four times a year for injections, Reginald Sanders, MD, president of the American Society of Retina Specialist, Chicago, and a retina specialist in Washington, DC, told this news organization. “Now with injections, you have the anxiety of getting the injections, you have the inconvenience of coming in on a regular basis to get the injections, and you have mild discomfort — but you don’t go blind,” Dr. Sanders said.
Studies have shown patients with AMD or diabetic macular edema are better off getting more frequent injections, but still drug developers are seeking the holy grail of fewer injections. “How do we make these treatments last longer?” Dr. Sanders said. “Durability has become the catchword in our field. Instead of lasting a month or 2, can it last 3 months? Can it last 6 months? Or even a year? Can you get one injection and be done with it?”
Or, no injection at all?
“We’re looking for incremental improvements and longer-acting drugs, trying to lengthen the time between injections for wet AMD patients,” said David Boyer, MD, a retina specialist in Los Angeles.
Two Drugs May Be Better Than One
One combination treatment, sozinibercept, targets VEGF-C and D. The therapy is in two phase 3 trials: One in combination with aflibercept 2 mg (Eylea), which targets VEGF-A and B along with placental growth factor, and the other in combination with ranibizumab, which targets VEGF-A only. Data from one of those trials are expected this year, Dr. Boyer said.
A phase 2 trial last year reported that patients on combination sozinibercept-ranibizumab had significantly better visual acuity improvement than patients on ranibizumab only. The phase 3 trials ShORe with ranibizumab and COAST with aflibercept are evaluating improvements in visual acuity and retinal anatomy.
Two other combination therapies are in phase 2 trials, both with aflibercept: UBX1325 or foselutoclax, a small-molecule inhibitor of B-cell lymphoma extra-large, and umedaptanib pegol, an anti-fibroblast growth factor-2 aptamer. In the foselutoclax-aflibercept trial, 40% of patients didn’t need a supplemental anti-VEGF injection through 48 weeks, and 64% went treatment-free for more than 24 weeks.
Phase 2 trials of intravitreal umedaptanib pegol-aflibercept combination therapy in nAMD last year showed no superiority in vision and anatomical improvements over aflibercept alone but did find the combination halted disease progression, with “striking improvement” in previously untreated patients.
Novel Drug Delivery Systems
A host of novel drug delivery systems that could stretch out intervals between injections are in human trials. In 2021, the FDA approved one such system, the refillable port delivery system (PDS) implant with ranibizumab (Susvimo). PDS is a small cylinder implanted into the eye and filled with 100 mg/mL of ranibizumab, to be released for 6 months or so, then refilled in the physician’s office when it’s empty.
But new implants of PDS were halted in 2022 after the manufacturer, Genentech, received reports the device leaked. Genentech said it has fixed those problems and confirmed the device should again become available for implants this year.
The most advanced novel drug delivery system in clinical trials is EYP-1901, a depot that contains the tyrosine kinase inhibitor (TKI) vorolanib. The depot is inserted under the ocular surface, where it biodegrades over 6 months as it releases the drug. A phase 3 trial is due to start enrollment at midyear.
An intravitreal implant with the TKI axitinib (Axpaxli) is in a phase 3 trial in nAMD and is due to start a phase 3 trial in diabetic retinopathy this year. At least four other implants, some of which biodegrade as they release the active ingredient, are in phase 1 or 2 trials.
TKIs themselves are a drug class worth watching in retina, said Jennifer I. Lim, MD, director of the retina service at the University of Illinois Chicago and president of the Retina Society.
“With TKIs, which activate intracellularly, in combination with anti-VEGFs will result in enhanced durability and possibly more efficacy for AMD,” Dr. Lim said. “TKIs in the phase 2 studies showed a marked reduction in the need for anti-VEGF injections in previously difficult-to-treat, high-need patient.”
Potential for Orals and Topicals
Topical eye drops are commonly used for anti-glaucoma drugs and antibiotics and corticosteroids for eye infections and inflammation, but using them for retinal disease has been a challenge. By the time the drug reaches the back of the eye, it has lost much of its pharmacokinetic activity. Three drops are in clinical trials for diabetic eye disease, with one, OCS-01, a preservative-free formulation of the corticosteroid dexamethasone, scheduled this year to enter a phase 3 trial.
At least four oral tablets are in early-stage human trials for diabetic eye disease. Four others are in clinical trials to treat geographic atrophy or early-stage dry AMD. They include tinlarebant, which is in phase 3 trials for geographic atrophy and Stargardt disease, an inherited retinal disorder.
Two other oral tablets are in human trials for inherited retinal disease. Like tinlarebant, emixustat has been in a phase 3 trial for Stargardt disease but showed no clinically significant improvement in macular atrophy. An early readout of an ongoing phase 2 trial of glideuretinol, a modified form of vitamin A, demonstrated slowed growth of macular atrophy in Stargardt.
These new and emerging treatments may potentially enable retina specialists to manage a rapidly growing aging population more efficiently, Dr. Sanders said.
“We have to figure out, on one hand, how do we catch the disease earlier? Like in other fields of medicine, the earlier you treat someone, the better,” Dr. Sanders said. “And also, how do we efficiently see these patients earlier to get therapy? Using implants or more durable drugs may be able to help us to treat more people more efficiently.”
Dr. Lim disclosed financial relationships with AbbVie/Allergan, Adverum Biotechnologies, Alimera Sciences, Bausch + Lomb, Chengdu Kanghong Biotechnology, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RegenxBio, Santen, SparingVision, Stealth BioTherapeutics, Unity Biotechnology, and Viridian.
Dr. Boyer disclosed financial relationships with 4D Molecular Therapeutics, AbbVie/Allergan, Adverum Biotechnologies, Aldeyra Therapeutics, Alimera Sciences, Alkahest, Allegro, Amgen, Annexon Biosciences, Apellis Pharmaceuticals, AsclepiX Therapeutics, Aviceda Therapeutics, Bausch + Lomb, Bayer, Belite Bio, Clearside Biomedical, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Nano scope Therapeutics, Novartis, Ocugen, Oculist, Ocuphire Pharma, Opthea, Pfizer, Regeneron Pharmaceuticals, RegenxBio, Sanofi, Stilbite Zhuhai, Stealth BioTherapeutics, Thea Laboratories, and Unity Biotechnology. Dr. Sanders had no relevant disclosures.
A version of this article appeared on Medscape.com.
The burdens that monthly or every-other-month injections in the eye impose on patients with retinal diseases are well-known to be barriers to care for many people with these conditions. Making treatment less onerous has driven research into new treatments since the US Food and Drug Administration (FDA) approved ranibizumab (Lucentis) in 2006 as the first anti–vascular endothelial growth factor (VEGF) for the treatment of age-related macular degeneration (AMD) and other retinal diseases.
Those Several of those investigational therapies are poised to hit meaningful milestones in 2024.
Regular Eye Injections: How We Got Here
Ranibizumab originally received approval as a monthly injection. Since then, protocols have evolved to space those injections out to every other month in some, but not all, patients.
New drugs have emerged that require less frequent injections. In 2022, the anti-VEGF and angiopoietin-2 inhibitor faricimab (Vabysmo) was approved for dosing up to every 4 months. Last year, the FDA approved a high-dose formulation of the anti-VEGF treatment aflibercept 8 mg (Eylea HD) to be given every 2-4 months, as well.
But even these treatments require patients going to the office at least three or four times a year for injections, Reginald Sanders, MD, president of the American Society of Retina Specialist, Chicago, and a retina specialist in Washington, DC, told this news organization. “Now with injections, you have the anxiety of getting the injections, you have the inconvenience of coming in on a regular basis to get the injections, and you have mild discomfort — but you don’t go blind,” Dr. Sanders said.
Studies have shown patients with AMD or diabetic macular edema are better off getting more frequent injections, but still drug developers are seeking the holy grail of fewer injections. “How do we make these treatments last longer?” Dr. Sanders said. “Durability has become the catchword in our field. Instead of lasting a month or 2, can it last 3 months? Can it last 6 months? Or even a year? Can you get one injection and be done with it?”
Or, no injection at all?
“We’re looking for incremental improvements and longer-acting drugs, trying to lengthen the time between injections for wet AMD patients,” said David Boyer, MD, a retina specialist in Los Angeles.
Two Drugs May Be Better Than One
One combination treatment, sozinibercept, targets VEGF-C and D. The therapy is in two phase 3 trials: One in combination with aflibercept 2 mg (Eylea), which targets VEGF-A and B along with placental growth factor, and the other in combination with ranibizumab, which targets VEGF-A only. Data from one of those trials are expected this year, Dr. Boyer said.
A phase 2 trial last year reported that patients on combination sozinibercept-ranibizumab had significantly better visual acuity improvement than patients on ranibizumab only. The phase 3 trials ShORe with ranibizumab and COAST with aflibercept are evaluating improvements in visual acuity and retinal anatomy.
Two other combination therapies are in phase 2 trials, both with aflibercept: UBX1325 or foselutoclax, a small-molecule inhibitor of B-cell lymphoma extra-large, and umedaptanib pegol, an anti-fibroblast growth factor-2 aptamer. In the foselutoclax-aflibercept trial, 40% of patients didn’t need a supplemental anti-VEGF injection through 48 weeks, and 64% went treatment-free for more than 24 weeks.
Phase 2 trials of intravitreal umedaptanib pegol-aflibercept combination therapy in nAMD last year showed no superiority in vision and anatomical improvements over aflibercept alone but did find the combination halted disease progression, with “striking improvement” in previously untreated patients.
Novel Drug Delivery Systems
A host of novel drug delivery systems that could stretch out intervals between injections are in human trials. In 2021, the FDA approved one such system, the refillable port delivery system (PDS) implant with ranibizumab (Susvimo). PDS is a small cylinder implanted into the eye and filled with 100 mg/mL of ranibizumab, to be released for 6 months or so, then refilled in the physician’s office when it’s empty.
But new implants of PDS were halted in 2022 after the manufacturer, Genentech, received reports the device leaked. Genentech said it has fixed those problems and confirmed the device should again become available for implants this year.
The most advanced novel drug delivery system in clinical trials is EYP-1901, a depot that contains the tyrosine kinase inhibitor (TKI) vorolanib. The depot is inserted under the ocular surface, where it biodegrades over 6 months as it releases the drug. A phase 3 trial is due to start enrollment at midyear.
An intravitreal implant with the TKI axitinib (Axpaxli) is in a phase 3 trial in nAMD and is due to start a phase 3 trial in diabetic retinopathy this year. At least four other implants, some of which biodegrade as they release the active ingredient, are in phase 1 or 2 trials.
TKIs themselves are a drug class worth watching in retina, said Jennifer I. Lim, MD, director of the retina service at the University of Illinois Chicago and president of the Retina Society.
“With TKIs, which activate intracellularly, in combination with anti-VEGFs will result in enhanced durability and possibly more efficacy for AMD,” Dr. Lim said. “TKIs in the phase 2 studies showed a marked reduction in the need for anti-VEGF injections in previously difficult-to-treat, high-need patient.”
Potential for Orals and Topicals
Topical eye drops are commonly used for anti-glaucoma drugs and antibiotics and corticosteroids for eye infections and inflammation, but using them for retinal disease has been a challenge. By the time the drug reaches the back of the eye, it has lost much of its pharmacokinetic activity. Three drops are in clinical trials for diabetic eye disease, with one, OCS-01, a preservative-free formulation of the corticosteroid dexamethasone, scheduled this year to enter a phase 3 trial.
At least four oral tablets are in early-stage human trials for diabetic eye disease. Four others are in clinical trials to treat geographic atrophy or early-stage dry AMD. They include tinlarebant, which is in phase 3 trials for geographic atrophy and Stargardt disease, an inherited retinal disorder.
Two other oral tablets are in human trials for inherited retinal disease. Like tinlarebant, emixustat has been in a phase 3 trial for Stargardt disease but showed no clinically significant improvement in macular atrophy. An early readout of an ongoing phase 2 trial of glideuretinol, a modified form of vitamin A, demonstrated slowed growth of macular atrophy in Stargardt.
These new and emerging treatments may potentially enable retina specialists to manage a rapidly growing aging population more efficiently, Dr. Sanders said.
“We have to figure out, on one hand, how do we catch the disease earlier? Like in other fields of medicine, the earlier you treat someone, the better,” Dr. Sanders said. “And also, how do we efficiently see these patients earlier to get therapy? Using implants or more durable drugs may be able to help us to treat more people more efficiently.”
Dr. Lim disclosed financial relationships with AbbVie/Allergan, Adverum Biotechnologies, Alimera Sciences, Bausch + Lomb, Chengdu Kanghong Biotechnology, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RegenxBio, Santen, SparingVision, Stealth BioTherapeutics, Unity Biotechnology, and Viridian.
Dr. Boyer disclosed financial relationships with 4D Molecular Therapeutics, AbbVie/Allergan, Adverum Biotechnologies, Aldeyra Therapeutics, Alimera Sciences, Alkahest, Allegro, Amgen, Annexon Biosciences, Apellis Pharmaceuticals, AsclepiX Therapeutics, Aviceda Therapeutics, Bausch + Lomb, Bayer, Belite Bio, Clearside Biomedical, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Nano scope Therapeutics, Novartis, Ocugen, Oculist, Ocuphire Pharma, Opthea, Pfizer, Regeneron Pharmaceuticals, RegenxBio, Sanofi, Stilbite Zhuhai, Stealth BioTherapeutics, Thea Laboratories, and Unity Biotechnology. Dr. Sanders had no relevant disclosures.
A version of this article appeared on Medscape.com.
The burdens that monthly or every-other-month injections in the eye impose on patients with retinal diseases are well-known to be barriers to care for many people with these conditions. Making treatment less onerous has driven research into new treatments since the US Food and Drug Administration (FDA) approved ranibizumab (Lucentis) in 2006 as the first anti–vascular endothelial growth factor (VEGF) for the treatment of age-related macular degeneration (AMD) and other retinal diseases.
Those Several of those investigational therapies are poised to hit meaningful milestones in 2024.
Regular Eye Injections: How We Got Here
Ranibizumab originally received approval as a monthly injection. Since then, protocols have evolved to space those injections out to every other month in some, but not all, patients.
New drugs have emerged that require less frequent injections. In 2022, the anti-VEGF and angiopoietin-2 inhibitor faricimab (Vabysmo) was approved for dosing up to every 4 months. Last year, the FDA approved a high-dose formulation of the anti-VEGF treatment aflibercept 8 mg (Eylea HD) to be given every 2-4 months, as well.
But even these treatments require patients going to the office at least three or four times a year for injections, Reginald Sanders, MD, president of the American Society of Retina Specialist, Chicago, and a retina specialist in Washington, DC, told this news organization. “Now with injections, you have the anxiety of getting the injections, you have the inconvenience of coming in on a regular basis to get the injections, and you have mild discomfort — but you don’t go blind,” Dr. Sanders said.
Studies have shown patients with AMD or diabetic macular edema are better off getting more frequent injections, but still drug developers are seeking the holy grail of fewer injections. “How do we make these treatments last longer?” Dr. Sanders said. “Durability has become the catchword in our field. Instead of lasting a month or 2, can it last 3 months? Can it last 6 months? Or even a year? Can you get one injection and be done with it?”
Or, no injection at all?
“We’re looking for incremental improvements and longer-acting drugs, trying to lengthen the time between injections for wet AMD patients,” said David Boyer, MD, a retina specialist in Los Angeles.
Two Drugs May Be Better Than One
One combination treatment, sozinibercept, targets VEGF-C and D. The therapy is in two phase 3 trials: One in combination with aflibercept 2 mg (Eylea), which targets VEGF-A and B along with placental growth factor, and the other in combination with ranibizumab, which targets VEGF-A only. Data from one of those trials are expected this year, Dr. Boyer said.
A phase 2 trial last year reported that patients on combination sozinibercept-ranibizumab had significantly better visual acuity improvement than patients on ranibizumab only. The phase 3 trials ShORe with ranibizumab and COAST with aflibercept are evaluating improvements in visual acuity and retinal anatomy.
Two other combination therapies are in phase 2 trials, both with aflibercept: UBX1325 or foselutoclax, a small-molecule inhibitor of B-cell lymphoma extra-large, and umedaptanib pegol, an anti-fibroblast growth factor-2 aptamer. In the foselutoclax-aflibercept trial, 40% of patients didn’t need a supplemental anti-VEGF injection through 48 weeks, and 64% went treatment-free for more than 24 weeks.
Phase 2 trials of intravitreal umedaptanib pegol-aflibercept combination therapy in nAMD last year showed no superiority in vision and anatomical improvements over aflibercept alone but did find the combination halted disease progression, with “striking improvement” in previously untreated patients.
Novel Drug Delivery Systems
A host of novel drug delivery systems that could stretch out intervals between injections are in human trials. In 2021, the FDA approved one such system, the refillable port delivery system (PDS) implant with ranibizumab (Susvimo). PDS is a small cylinder implanted into the eye and filled with 100 mg/mL of ranibizumab, to be released for 6 months or so, then refilled in the physician’s office when it’s empty.
But new implants of PDS were halted in 2022 after the manufacturer, Genentech, received reports the device leaked. Genentech said it has fixed those problems and confirmed the device should again become available for implants this year.
The most advanced novel drug delivery system in clinical trials is EYP-1901, a depot that contains the tyrosine kinase inhibitor (TKI) vorolanib. The depot is inserted under the ocular surface, where it biodegrades over 6 months as it releases the drug. A phase 3 trial is due to start enrollment at midyear.
An intravitreal implant with the TKI axitinib (Axpaxli) is in a phase 3 trial in nAMD and is due to start a phase 3 trial in diabetic retinopathy this year. At least four other implants, some of which biodegrade as they release the active ingredient, are in phase 1 or 2 trials.
TKIs themselves are a drug class worth watching in retina, said Jennifer I. Lim, MD, director of the retina service at the University of Illinois Chicago and president of the Retina Society.
“With TKIs, which activate intracellularly, in combination with anti-VEGFs will result in enhanced durability and possibly more efficacy for AMD,” Dr. Lim said. “TKIs in the phase 2 studies showed a marked reduction in the need for anti-VEGF injections in previously difficult-to-treat, high-need patient.”
Potential for Orals and Topicals
Topical eye drops are commonly used for anti-glaucoma drugs and antibiotics and corticosteroids for eye infections and inflammation, but using them for retinal disease has been a challenge. By the time the drug reaches the back of the eye, it has lost much of its pharmacokinetic activity. Three drops are in clinical trials for diabetic eye disease, with one, OCS-01, a preservative-free formulation of the corticosteroid dexamethasone, scheduled this year to enter a phase 3 trial.
At least four oral tablets are in early-stage human trials for diabetic eye disease. Four others are in clinical trials to treat geographic atrophy or early-stage dry AMD. They include tinlarebant, which is in phase 3 trials for geographic atrophy and Stargardt disease, an inherited retinal disorder.
Two other oral tablets are in human trials for inherited retinal disease. Like tinlarebant, emixustat has been in a phase 3 trial for Stargardt disease but showed no clinically significant improvement in macular atrophy. An early readout of an ongoing phase 2 trial of glideuretinol, a modified form of vitamin A, demonstrated slowed growth of macular atrophy in Stargardt.
These new and emerging treatments may potentially enable retina specialists to manage a rapidly growing aging population more efficiently, Dr. Sanders said.
“We have to figure out, on one hand, how do we catch the disease earlier? Like in other fields of medicine, the earlier you treat someone, the better,” Dr. Sanders said. “And also, how do we efficiently see these patients earlier to get therapy? Using implants or more durable drugs may be able to help us to treat more people more efficiently.”
Dr. Lim disclosed financial relationships with AbbVie/Allergan, Adverum Biotechnologies, Alimera Sciences, Bausch + Lomb, Chengdu Kanghong Biotechnology, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RegenxBio, Santen, SparingVision, Stealth BioTherapeutics, Unity Biotechnology, and Viridian.
Dr. Boyer disclosed financial relationships with 4D Molecular Therapeutics, AbbVie/Allergan, Adverum Biotechnologies, Aldeyra Therapeutics, Alimera Sciences, Alkahest, Allegro, Amgen, Annexon Biosciences, Apellis Pharmaceuticals, AsclepiX Therapeutics, Aviceda Therapeutics, Bausch + Lomb, Bayer, Belite Bio, Clearside Biomedical, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Nano scope Therapeutics, Novartis, Ocugen, Oculist, Ocuphire Pharma, Opthea, Pfizer, Regeneron Pharmaceuticals, RegenxBio, Sanofi, Stilbite Zhuhai, Stealth BioTherapeutics, Thea Laboratories, and Unity Biotechnology. Dr. Sanders had no relevant disclosures.
A version of this article appeared on Medscape.com.
DMARDs Restore GI Microbiota Balance in RA But Ability to Predict Response Falls Short
Patients with rheumatoid arthritis (RA) whose symptoms improved after they started taking nonbiologic disease-modifying antirheumatic drugs also demonstrated restored balance in their oral and gut flora, which could potentially serve as a marker of how they’ll respond to DMARDs, an observational study in the United Kingdom found.
Reporting in the journal Rheumatology, researchers led by Nathan Danckert, PhD, a genetic epidemiology researcher at King’s College London, and Maxim Freidin, PhD, of the Queen Mary University of London, London, England, evaluated stool and saliva samples of 144 people recently diagnosed with RA before and after they started DMARD therapy.
“We identified a partial restoration of the microbiome to a more eubiotic state in RA patients at 6 weeks and 12 weeks of DMARD treatment in participants [who] responded well to DMARD therapy,” they wrote. “This was further supported by long-term (> 1 year) treated DMARD RA participants with similar community shifts.” Microbiomes, they said, are “a promising diagnostic tool” for directing DMARD therapy.
Study Goal Not Met
The goal of the study was to determine whether the microbiome of patients before they began treatment with DMARDs could predict their response to therapy. The patients were enrolled in the IMRABIOME study. Eligible patients had inflammatory arthritis symptoms for a year or less and met the clinical criteria for RA. Most patients were taking methotrexate (134 at baseline, 77 at 12 weeks), but study participants were also taking sulfasalazine (16 at baseline, 14 at 12 weeks) or hydroxychloroquine (58 at baseline, 45 at 12 weeks) either in combination or as a stand-alone treatment.
The study found a total of 26 different stool microbes that decreased in patients who had a minimal clinically important improvement (MCII) after starting DMARD therapy. At 6 weeks, the most significant declines were in Prevotella species. At 12 weeks, the greatest declines were in Streptococcus.
The researchers also developed models that used gut and oral metagenomes to predict MCII in patients starting DMARD therapy. They used a previously published microbiome dataset as a validation cohort for the model, but they acknowledged their models “were not as strong” as three previously published models. “Our findings support the hypothesis of DMARD restoration of a eubiotic gut microbiome when patient and treatment align,” the authors wrote.
They noted they had anticipated finding baseline microbiome samples that would help predict treatment responses. While baseline evaluation didn’t differentiate between responders and nonresponders, they wrote that a longitudinal analysis demonstrated changing microbiota and a positive response to therapy, with declining levels of Prevotella and Streptococcus species most pronounced at 6 and 12 weeks, respectively.
“Microbiomes provide a promising diagnostic tool for guiding therapeutic decisions in the future,” the study authors wrote.
Commentary
In commenting on the study, Gregg J. Silverman, MD, professor of medicine and pathology at the New York University School of Medicine, New York City, said it “was carefully performed, technically it was actually quite impressive, and the scale of the study actually was quite suitable.”
However, the study fell short of achieving its primary goal of using the microbiome to predict treatment response, he said. “Basically, they could not find there was anything they could correlate with clinical response rates, although they did find that the presence or absence of certain bacteria at 6 weeks or 12 weeks into treatment correlated with a clinical response,” he said.
The multiplicity of DMARDs used by the study population was “one of the complicating factors” of the study, Dr. Silverman said. “It would’ve been a much more easily interpreted study if it used just a single agent like methotrexate,” he said. “I think that’s problematic, but I do think this contributes to getting us a little further down the road of understanding how the microbiome can influence the pathogenesis of rheumatoid arthritis response to treatment.”
One of the questions surrounding the microbiome changes is whether they occurred because of the effect of the therapy itself or because the disease activity subsides, Dr. Silverman said. “So, you’re not sure if it’s cause or effect. There’s evidence to suggest that either could be true.”
This study adds to a 2022 study that found a similar effect with methotrexate, Dr. Silverman said. “They considered a lot of variables, and they considered a lot of potential confounding effects,” he said. “So, their data were well-considered, and they will actually hold up over time and contribute to the next range of studies that will be performed, no doubt, in this area.”
It would be better if those future studies focused on just one DMARD drug and studied the recovered bacteria in animal models to gain a better understanding of how they correlate to pathogenesis, Dr. Silverman added.
The study received funding from Versus Arthritis. Dr. Danckert, Dr. Freidin, and coauthors, as well as Dr. Silverman, reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with rheumatoid arthritis (RA) whose symptoms improved after they started taking nonbiologic disease-modifying antirheumatic drugs also demonstrated restored balance in their oral and gut flora, which could potentially serve as a marker of how they’ll respond to DMARDs, an observational study in the United Kingdom found.
Reporting in the journal Rheumatology, researchers led by Nathan Danckert, PhD, a genetic epidemiology researcher at King’s College London, and Maxim Freidin, PhD, of the Queen Mary University of London, London, England, evaluated stool and saliva samples of 144 people recently diagnosed with RA before and after they started DMARD therapy.
“We identified a partial restoration of the microbiome to a more eubiotic state in RA patients at 6 weeks and 12 weeks of DMARD treatment in participants [who] responded well to DMARD therapy,” they wrote. “This was further supported by long-term (> 1 year) treated DMARD RA participants with similar community shifts.” Microbiomes, they said, are “a promising diagnostic tool” for directing DMARD therapy.
Study Goal Not Met
The goal of the study was to determine whether the microbiome of patients before they began treatment with DMARDs could predict their response to therapy. The patients were enrolled in the IMRABIOME study. Eligible patients had inflammatory arthritis symptoms for a year or less and met the clinical criteria for RA. Most patients were taking methotrexate (134 at baseline, 77 at 12 weeks), but study participants were also taking sulfasalazine (16 at baseline, 14 at 12 weeks) or hydroxychloroquine (58 at baseline, 45 at 12 weeks) either in combination or as a stand-alone treatment.
The study found a total of 26 different stool microbes that decreased in patients who had a minimal clinically important improvement (MCII) after starting DMARD therapy. At 6 weeks, the most significant declines were in Prevotella species. At 12 weeks, the greatest declines were in Streptococcus.
The researchers also developed models that used gut and oral metagenomes to predict MCII in patients starting DMARD therapy. They used a previously published microbiome dataset as a validation cohort for the model, but they acknowledged their models “were not as strong” as three previously published models. “Our findings support the hypothesis of DMARD restoration of a eubiotic gut microbiome when patient and treatment align,” the authors wrote.
They noted they had anticipated finding baseline microbiome samples that would help predict treatment responses. While baseline evaluation didn’t differentiate between responders and nonresponders, they wrote that a longitudinal analysis demonstrated changing microbiota and a positive response to therapy, with declining levels of Prevotella and Streptococcus species most pronounced at 6 and 12 weeks, respectively.
“Microbiomes provide a promising diagnostic tool for guiding therapeutic decisions in the future,” the study authors wrote.
Commentary
In commenting on the study, Gregg J. Silverman, MD, professor of medicine and pathology at the New York University School of Medicine, New York City, said it “was carefully performed, technically it was actually quite impressive, and the scale of the study actually was quite suitable.”
However, the study fell short of achieving its primary goal of using the microbiome to predict treatment response, he said. “Basically, they could not find there was anything they could correlate with clinical response rates, although they did find that the presence or absence of certain bacteria at 6 weeks or 12 weeks into treatment correlated with a clinical response,” he said.
The multiplicity of DMARDs used by the study population was “one of the complicating factors” of the study, Dr. Silverman said. “It would’ve been a much more easily interpreted study if it used just a single agent like methotrexate,” he said. “I think that’s problematic, but I do think this contributes to getting us a little further down the road of understanding how the microbiome can influence the pathogenesis of rheumatoid arthritis response to treatment.”
One of the questions surrounding the microbiome changes is whether they occurred because of the effect of the therapy itself or because the disease activity subsides, Dr. Silverman said. “So, you’re not sure if it’s cause or effect. There’s evidence to suggest that either could be true.”
This study adds to a 2022 study that found a similar effect with methotrexate, Dr. Silverman said. “They considered a lot of variables, and they considered a lot of potential confounding effects,” he said. “So, their data were well-considered, and they will actually hold up over time and contribute to the next range of studies that will be performed, no doubt, in this area.”
It would be better if those future studies focused on just one DMARD drug and studied the recovered bacteria in animal models to gain a better understanding of how they correlate to pathogenesis, Dr. Silverman added.
The study received funding from Versus Arthritis. Dr. Danckert, Dr. Freidin, and coauthors, as well as Dr. Silverman, reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with rheumatoid arthritis (RA) whose symptoms improved after they started taking nonbiologic disease-modifying antirheumatic drugs also demonstrated restored balance in their oral and gut flora, which could potentially serve as a marker of how they’ll respond to DMARDs, an observational study in the United Kingdom found.
Reporting in the journal Rheumatology, researchers led by Nathan Danckert, PhD, a genetic epidemiology researcher at King’s College London, and Maxim Freidin, PhD, of the Queen Mary University of London, London, England, evaluated stool and saliva samples of 144 people recently diagnosed with RA before and after they started DMARD therapy.
“We identified a partial restoration of the microbiome to a more eubiotic state in RA patients at 6 weeks and 12 weeks of DMARD treatment in participants [who] responded well to DMARD therapy,” they wrote. “This was further supported by long-term (> 1 year) treated DMARD RA participants with similar community shifts.” Microbiomes, they said, are “a promising diagnostic tool” for directing DMARD therapy.
Study Goal Not Met
The goal of the study was to determine whether the microbiome of patients before they began treatment with DMARDs could predict their response to therapy. The patients were enrolled in the IMRABIOME study. Eligible patients had inflammatory arthritis symptoms for a year or less and met the clinical criteria for RA. Most patients were taking methotrexate (134 at baseline, 77 at 12 weeks), but study participants were also taking sulfasalazine (16 at baseline, 14 at 12 weeks) or hydroxychloroquine (58 at baseline, 45 at 12 weeks) either in combination or as a stand-alone treatment.
The study found a total of 26 different stool microbes that decreased in patients who had a minimal clinically important improvement (MCII) after starting DMARD therapy. At 6 weeks, the most significant declines were in Prevotella species. At 12 weeks, the greatest declines were in Streptococcus.
The researchers also developed models that used gut and oral metagenomes to predict MCII in patients starting DMARD therapy. They used a previously published microbiome dataset as a validation cohort for the model, but they acknowledged their models “were not as strong” as three previously published models. “Our findings support the hypothesis of DMARD restoration of a eubiotic gut microbiome when patient and treatment align,” the authors wrote.
They noted they had anticipated finding baseline microbiome samples that would help predict treatment responses. While baseline evaluation didn’t differentiate between responders and nonresponders, they wrote that a longitudinal analysis demonstrated changing microbiota and a positive response to therapy, with declining levels of Prevotella and Streptococcus species most pronounced at 6 and 12 weeks, respectively.
“Microbiomes provide a promising diagnostic tool for guiding therapeutic decisions in the future,” the study authors wrote.
Commentary
In commenting on the study, Gregg J. Silverman, MD, professor of medicine and pathology at the New York University School of Medicine, New York City, said it “was carefully performed, technically it was actually quite impressive, and the scale of the study actually was quite suitable.”
However, the study fell short of achieving its primary goal of using the microbiome to predict treatment response, he said. “Basically, they could not find there was anything they could correlate with clinical response rates, although they did find that the presence or absence of certain bacteria at 6 weeks or 12 weeks into treatment correlated with a clinical response,” he said.
The multiplicity of DMARDs used by the study population was “one of the complicating factors” of the study, Dr. Silverman said. “It would’ve been a much more easily interpreted study if it used just a single agent like methotrexate,” he said. “I think that’s problematic, but I do think this contributes to getting us a little further down the road of understanding how the microbiome can influence the pathogenesis of rheumatoid arthritis response to treatment.”
One of the questions surrounding the microbiome changes is whether they occurred because of the effect of the therapy itself or because the disease activity subsides, Dr. Silverman said. “So, you’re not sure if it’s cause or effect. There’s evidence to suggest that either could be true.”
This study adds to a 2022 study that found a similar effect with methotrexate, Dr. Silverman said. “They considered a lot of variables, and they considered a lot of potential confounding effects,” he said. “So, their data were well-considered, and they will actually hold up over time and contribute to the next range of studies that will be performed, no doubt, in this area.”
It would be better if those future studies focused on just one DMARD drug and studied the recovered bacteria in animal models to gain a better understanding of how they correlate to pathogenesis, Dr. Silverman added.
The study received funding from Versus Arthritis. Dr. Danckert, Dr. Freidin, and coauthors, as well as Dr. Silverman, reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM RHEUMATOLOGY
Prednisolone May Improve MOH Withdrawal
, an observational study out of South Korea has found.
The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034) 
The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
Study methods
The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.
The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.
Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.
Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.
The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.
Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
Commentary
Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.
Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.
“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”
He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.
Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.
, an observational study out of South Korea has found.
The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)
The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
Study methods
The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.
The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.
Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.
Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.
The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.
Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
Commentary
Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.
Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.
“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”
He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.
Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.
, an observational study out of South Korea has found.
The study, a post-hoc analysis of the RELEASE multicenter observational cohort study of MOH patients in South Korea, found that patients who took prednisolone as a bridge therapy in the early phase of withdrawal from headache medications, or detoxification, had statistically significant higher rates of MOH reversal at 3 months after enrollment than those who did not, 73.8% versus 57.8% (P = .034)
The reversal trend also was noted at 1 month after treatment, the study authors, led by Mi Ji Lee, MD, PhD, an assistant professor at Seoul National University Hospital, Seoul, South Korea, wrote. “Although an observational study cannot draw a definitive conclusion, our study supports the use of prednisolone for the treatment of MOH in a real-world setting,” Dr. Lee and colleagues wrote.
Study methods
The study was a post hoc analysis of the RELEASE study, which stands for Registry for Load and Management of Medication Overuse Headache. RELEASE is a multicenter observational cohort study that has been ongoing in South Korea since April 2020. The post hoc analysis included 309 patients, 59 of whom received prednisolone at a varying dose of 10-40 mg a day, with a varying course of 5-14 days. About 74% of patients (228 of 309) completed the 3-month follow-up period, including 41 in the prednisolone group.
The study used three different forms of medication withdrawal before the patients started prednisolone therapy: abrupt discontinuation; gradual discontinuation concurrent with starting prednisolone; and no withdrawal.
Because of the observational nature of the RELEASE study, participating physicians prescribed prednisolone at their own discretion. The study authors noted prednisolone use was neither randomized nor controlled, which they acknowledged as a limitation.
Dr. Lee and colleagues also acknowledged that newer calcitonin gene–related peptide (CGRP) receptor antagonists may not require detoxification to reverse MOH, but that those therapies are not always available for a variety of reasons, such as reimbursement restrictions, regional distribution issues, and financial issues.
The study also evaluated a number of secondary outcomes. For example, 72% of prednisolone patients achieved MOH reversal 1 month after starting treatment versus 54.9% of the nonprednisolone patients. (P = .33). Prednisolone users also had greater reductions in acute medication days (AMD) at 1 month and scores on headache impact test-6 (HIT-6) at 6 months.
Dr. Lee and colleagues noted that the concept of detoxification, or discontinuing medication overuse, as a treatment for MOH has been controversial due to a lack of high-quality evidence to support the approach. “Nevertheless,” they wrote, “several experts still put withdrawal of medication overuse as an important step of MOH treatment in clinical practice despite limited evidence.”
Commentary
Alan Rapoport, MD, a clinical professor of neurology at the David Geffen School of Medicine at University of California, Los Angeles, noted a number of limitations with the study. “It wasn’t a unified population of patients,” he said, “which makes it a little harder to say this medicine worked — worked on whom?” The lack of a treatment regimen — the varied dosing and treatment durations, along with the different withdrawal approaches — are further limitations, Dr. Rapoport said.
Nonetheless, the study is an important addition to the evidence on how to manage medication withdrawal in MOH, said Dr. Rapoport, a past president of the International Headache Society and founder and director emeritus of the New England Center for Headache in Stamford, Connecticut, who has a keen interest in MOH research.
“I think this shows to some extent, although it doesn’t prove it because it’s a whole mixture of patients who were all treated differently by different doctors, but when you put them all together the patients who took steroids did better than the patients who did not,” he said. “The study authors did the best they could with the information they had.”
He termed the study “well-done by well-known authors in South Korea.” As medications such as CGRP receptor antagonists and monoclonal antibodies that target CGRP and its receptors become more available, MOH patients “may not need actual detoxification or steroids in their treatment,” Dr. Rapoport said.
Dr. Lee and co-authors have no disclosures. Dr. Rapoport is editor-in-chief of Neurology Reviews. He disclosed relationships with AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica.
FROM HEADACHE
2024 Will See Major Advances in Glaucoma Care
Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.
Undry Those Eyes
Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.
“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.
“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”
The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.
This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:
- Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
- Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
- AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.
The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.
In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.
“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.
Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.
A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.
Looking Ahead
A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.
Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.
Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.
Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.
Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.
As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.
Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.
Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.
A version of this article appeared on Medscape.com.
Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.
Undry Those Eyes
Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.
“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.
“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”
The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.
This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:
- Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
- Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
- AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.
The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.
In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.
“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.
Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.
A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.
Looking Ahead
A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.
Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.
Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.
Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.
Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.
As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.
Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.
Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.
A version of this article appeared on Medscape.com.
Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.
Undry Those Eyes
Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.
“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.
“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”
The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.
This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:
- Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
- Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
- AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.
The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.
In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.
“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.
Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.
A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.
Looking Ahead
A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.
Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.
Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.
Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.
Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.
As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.
Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.
Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.
A version of this article appeared on Medscape.com.
Redosing Rituximab to Maintain ANCA Vasculitis Remission: When Is Best?
Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks.
“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.
“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”
Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
Study Results
Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.
The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.
The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.
He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”
Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
Findings in Context
This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.
“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”
The size of the study population was a strength of the study, Dr. Hylland said.
He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.
“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.
The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.
“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.
The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.
A version of this article appeared on Medscape.com.
Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks.
“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.
“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”
Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
Study Results
Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.
The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.
The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.
He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”
Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
Findings in Context
This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.
“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”
The size of the study population was a strength of the study, Dr. Hylland said.
He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.
“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.
The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.
“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.
The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.
A version of this article appeared on Medscape.com.
Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks.
“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.
“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”
Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
Study Results
Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.
The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.
The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.
He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”
Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
Findings in Context
This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.
“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”
The size of the study population was a strength of the study, Dr. Hylland said.
He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.
“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.
The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.
“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.
The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Monitoring Tech for Pulmonary Disorders Moving Beyond Wearables
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
FDA approves implant for glaucoma
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
Report: CKD Severity Linked to Thinning of Retina, Choroid Layers
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
New PCSK9 inhibitor allows 3-month treatment intervals
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
AT AHA 2023
Cardiologists, patients can talk drug costs
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
AT AHA 2023