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Early RA Diagnosis and Treatment Lowers Treatment Costs
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.
METHODOLOGY:
- The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
- Symptom duration was defined as time between symptom onset and first clinic visit.
- Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
- Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
- Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.
TAKEAWAY:
- For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
- For antibody-positive RA, costs were 19% higher in the late-treatment group.
- In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.
IN PRACTICE:
“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”
SOURCE:
The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases.
LIMITATIONS:
The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.
DISCLOSURES:
This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Pyzchiva Receives FDA Approval as Third Ustekinumab Biosimilar
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.
In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.
Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:
- Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy
- Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis
It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial.
Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).
Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.
A version of this article appeared on Medscape.com.
Form of B12 Deficiency Affecting the Central Nervous System May Be New Autoimmune Disease
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Discovered while studying a puzzling case of one patient with inexplicable neurological systems, the same autoantibody was detected in a small percentage of healthy individuals and was nearly four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE).
“I didn’t think this single investigation was going to yield a broader phenomenon with other patients,” lead author John V. Pluvinage, MD, PhD, a neurology resident at the University of California San Francisco, said in an interview. “It started as an N-of-one study just based on scientific curiosity.”
“It’s a beautifully done study,” added Betty Diamond, MD, director of the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commenting on the research. It uncovers “yet another example of a disease where antibodies getting into the brain are the problem.”
The research was published in Science Translational Medicine.
The Patient
The investigation began in 2014 with a 67-year-old woman presenting with difficulty speaking, ataxia, and tremor. Her blood tests showed no signs of B12 deficiency, and testing for known autoantibodies came back negative.
Solving this mystery required a more exhaustive approach. The patient enrolled in a research study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing.
“We adapted this technology to screen for autoantibodies in an unbiased manner by displaying every peptide across the human proteome and then mixing those peptides with patient antibodies in order to figure out what the antibodies are binding to,” explained Dr. Pluvinage.
Using this method, he and colleagues discovered that this woman had autoantibodies that target CD320 — a receptor important in the cellular uptake of B12. While her blood tests were normal, B12 in the patient’s cerebral spinal fluid (CSF) was “nearly undetectable,” Dr. Pluvinage said. Using an in vitro model of the blood-brain barrier (BBB), the researchers determined that anti-CD320 impaired the transport of B12 across the BBB by targeting receptors on the cell surface.
Treating the patient with a combination of immunosuppressant medication and high-dose B12 supplementation increased B12 levels in the patient’s CSF and improved clinical symptoms.
Identifying More Cases
Dr. Pluvinage and colleagues tested the 254 other individuals enrolled in the neuroinflammatory disease study and identified seven participants with CSF anti-CD320 autoantibodies — four of whom had low B12 in the CSF.
In a group of healthy controls, anti-CD320 seropositivity was 6%, similar to the positivity rate in 132 paired serum and CSF samples from a cohort of patients with multiple sclerosis (5.7%). In this group of patients with multiple sclerosis, anti-CD320 presence in the blood was highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency.
Researchers also screened for anti-CD320 seropositivity in 408 patients with non-neurologic SLE and 28 patients with neuropsychiatric SLE and found that the autoantibody was nearly four times as prevalent in patients with neurologic symptoms (21.4%) compared with in those with non-neurologic SLE (5.6%).
“The clinical relevance of anti-CD320 in healthy controls remains uncertain,” the authors wrote. However, it is not uncommon to have healthy patients with known autoantibodies.
“There are always people who have autoantibodies who don’t get disease, and why that is we don’t know,” said Dr. Diamond. Some individuals may develop clinical symptoms later, or there may be other reasons why they are protected against disease.
Pluvinage is eager to follow some seropositive healthy individuals to track their neurologic health overtime, to see if the presence of anti-CD320 “alters their neurologic trajectories.”
Alternative Pathways
Lastly, Dr. Pluvinage and colleagues set out to explain why patients with anti-CD320 in their blood did not show any signs of B12 deficiency. They hypothesized that another receptor may be compensating and still allowing blood cells to take up B12. Using CRISPR screening, the team identified the low-density lipoprotein receptor as an alternative pathway to B12 uptake.
“These findings suggest a model in which anti-CD320 impairs transport of B12 across the BBB, leading to autoimmune B12 central deficiency (ABCD) with varied neurologic manifestations but sparing peripheral manifestations of B12 deficiency,” the authors wrote.
The work was supported by the National Institute of Mental Health, National Center for Chronic Disease Prevention and Health Promotion, Department of Defense, UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis Shared Resource Facility, National Multiple Sclerosis Society, Valhalla Foundation, and the Westridge Foundation. Dr. Pluvinage is a co-inventor on a patent application related to this work. Dr. Diamond had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SCIENCE TRANSLATIONAL MEDICINE
Psoriatic Arthritis Symptoms Relieved with TYK2 Inhibitor in Phase 2 Trial
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Psoriatic Arthritis Drug Candidate Sonelokimab Yields Significant Improvements in Phase 2 Trial
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FDA Proposes that Interchangeability Status for Biosimilars Doesn’t Need Switching Studies
The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.
“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”
An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.
While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”
However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.
“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.
“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.
The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.
“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”
An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.
While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”
However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.
“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.
“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.
The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.
“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”
An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.
While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”
However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.
“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.
“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.
The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.
A version of this article first appeared on Medscape.com.
Baricitinib Outperforms TNF Inhibitors in Real-World RA Trial
Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.
After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
Putting Safety Into the Equation
However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.
“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”
Both the ACR and European Alliance of Associations for Rheumatology guidelines recommend that patients who have not achieved target disease activity with csDMARDs can be prescribed either a Janus kinase (JAK) inhibitor or a TNF inhibitor as a treatment option, yet many physicians favor TNF inhibitors because of extensive clinical experience with the drug class and other factors such as biosimilar availability and cost, Celine van de Laar, MSc, of Erasmus University in Rotterdam, the Netherlands, and coauthors explained.
There are also notable safety concerns for using JAK inhibitors: Results from a large postmarketing clinical trial of tofacitinib prompted the US Food and Drug Administration to issue a boxed warning for the medication due to an increased risk for cardiovascular events, cancer, blood clots, and death, in comparison with TNF inhibitors. That warning now includes two other medications in the same drug class: baricitinib and upadacitinib. The European Medicines Agency has also issued guidance to minimize the risk for side effects for these medications.
Some randomized controlled trials have demonstrated that baricitinib “showed significant clinical improvements” in patients with RA, compared with adalimumab and placebo, but these trials do not always reflect treatment in the real world, the study authors wrote. The results were published in RMD Open.
Study Details
In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.
For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.
Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.
Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.
At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.
These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.
“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”
While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.
“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”
Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.
“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.
One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.
“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”
PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.
After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
Putting Safety Into the Equation
However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.
“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”
Both the ACR and European Alliance of Associations for Rheumatology guidelines recommend that patients who have not achieved target disease activity with csDMARDs can be prescribed either a Janus kinase (JAK) inhibitor or a TNF inhibitor as a treatment option, yet many physicians favor TNF inhibitors because of extensive clinical experience with the drug class and other factors such as biosimilar availability and cost, Celine van de Laar, MSc, of Erasmus University in Rotterdam, the Netherlands, and coauthors explained.
There are also notable safety concerns for using JAK inhibitors: Results from a large postmarketing clinical trial of tofacitinib prompted the US Food and Drug Administration to issue a boxed warning for the medication due to an increased risk for cardiovascular events, cancer, blood clots, and death, in comparison with TNF inhibitors. That warning now includes two other medications in the same drug class: baricitinib and upadacitinib. The European Medicines Agency has also issued guidance to minimize the risk for side effects for these medications.
Some randomized controlled trials have demonstrated that baricitinib “showed significant clinical improvements” in patients with RA, compared with adalimumab and placebo, but these trials do not always reflect treatment in the real world, the study authors wrote. The results were published in RMD Open.
Study Details
In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.
For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.
Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.
Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.
At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.
These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.
“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”
While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.
“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”
Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.
“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.
One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.
“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”
PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.
After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
Putting Safety Into the Equation
However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.
“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”
Both the ACR and European Alliance of Associations for Rheumatology guidelines recommend that patients who have not achieved target disease activity with csDMARDs can be prescribed either a Janus kinase (JAK) inhibitor or a TNF inhibitor as a treatment option, yet many physicians favor TNF inhibitors because of extensive clinical experience with the drug class and other factors such as biosimilar availability and cost, Celine van de Laar, MSc, of Erasmus University in Rotterdam, the Netherlands, and coauthors explained.
There are also notable safety concerns for using JAK inhibitors: Results from a large postmarketing clinical trial of tofacitinib prompted the US Food and Drug Administration to issue a boxed warning for the medication due to an increased risk for cardiovascular events, cancer, blood clots, and death, in comparison with TNF inhibitors. That warning now includes two other medications in the same drug class: baricitinib and upadacitinib. The European Medicines Agency has also issued guidance to minimize the risk for side effects for these medications.
Some randomized controlled trials have demonstrated that baricitinib “showed significant clinical improvements” in patients with RA, compared with adalimumab and placebo, but these trials do not always reflect treatment in the real world, the study authors wrote. The results were published in RMD Open.
Study Details
In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.
For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.
Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.
Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.
At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.
These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.
“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”
While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.
“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”
Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.
“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.
One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.
“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”
PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.
A version of this article first appeared on Medscape.com.
FROM RMD OPEN
What’s in a Name: Defining Difficult-to-Treat axSpA and PsA
Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.
Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.
“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.
According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.
“If you look into current clinical guidelines, you will see that there is no clear guidance,” on how to manage these patients, Dr. Poddubnyy continued. “In other similar recommendations for the treatment of axSpA, the only point which is clearly made with regards to nonresponders to effective anti-inflammatory treatment is to ‘check the diagnosis.’”
Multiple Reasons for Nonresponse
“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.
“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”
Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.
“There is a quite clear consensus within the community” that differentiation between these two groups is needed, Dr. Proft said.
The Definitions
Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”
The definition includes three criteria:
1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)
2) Signs suggestive of active/progressive disease, including at least one of the following:
- Moderate disease activity (according to validated composite measures including joint counts)
- Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
- Inability to taper glucocorticoid treatment
- Rapid radiographic progression (with or without signs of active disease)
- RA symptoms that are causing a reduction in quality of life
3) Symptom/sign management perceived as problematic by the rheumatologist or the patient
All three criteria must be met.
Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).
According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:
- Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
- Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
- Symptoms/signs of disease that are considered problematic by the provider or patient
The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.
The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
Looking Forward
The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.
“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”
Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.
“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.
On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.
“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.
Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.
Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.
“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.
According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.
“If you look into current clinical guidelines, you will see that there is no clear guidance,” on how to manage these patients, Dr. Poddubnyy continued. “In other similar recommendations for the treatment of axSpA, the only point which is clearly made with regards to nonresponders to effective anti-inflammatory treatment is to ‘check the diagnosis.’”
Multiple Reasons for Nonresponse
“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.
“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”
Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.
“There is a quite clear consensus within the community” that differentiation between these two groups is needed, Dr. Proft said.
The Definitions
Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”
The definition includes three criteria:
1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)
2) Signs suggestive of active/progressive disease, including at least one of the following:
- Moderate disease activity (according to validated composite measures including joint counts)
- Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
- Inability to taper glucocorticoid treatment
- Rapid radiographic progression (with or without signs of active disease)
- RA symptoms that are causing a reduction in quality of life
3) Symptom/sign management perceived as problematic by the rheumatologist or the patient
All three criteria must be met.
Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).
According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:
- Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
- Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
- Symptoms/signs of disease that are considered problematic by the provider or patient
The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.
The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
Looking Forward
The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.
“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”
Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.
“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.
On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.
“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.
Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.
Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.
“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.
According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.
“If you look into current clinical guidelines, you will see that there is no clear guidance,” on how to manage these patients, Dr. Poddubnyy continued. “In other similar recommendations for the treatment of axSpA, the only point which is clearly made with regards to nonresponders to effective anti-inflammatory treatment is to ‘check the diagnosis.’”
Multiple Reasons for Nonresponse
“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.
“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”
Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.
“There is a quite clear consensus within the community” that differentiation between these two groups is needed, Dr. Proft said.
The Definitions
Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”
The definition includes three criteria:
1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)
2) Signs suggestive of active/progressive disease, including at least one of the following:
- Moderate disease activity (according to validated composite measures including joint counts)
- Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
- Inability to taper glucocorticoid treatment
- Rapid radiographic progression (with or without signs of active disease)
- RA symptoms that are causing a reduction in quality of life
3) Symptom/sign management perceived as problematic by the rheumatologist or the patient
All three criteria must be met.
Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).
According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:
- Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
- Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
- Symptoms/signs of disease that are considered problematic by the provider or patient
The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.
The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
Looking Forward
The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.
“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”
Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.
“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.
On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.
“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.
Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
FROM SPARTAN 2024
FDA Approves Polyarticular JIA Indication for Sarilumab
The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb).
“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release.
It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation.
“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.”
Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD).
In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper.
For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs.
“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.”
The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb).
“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release.
It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation.
“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.”
Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD).
In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper.
For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs.
“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.”
The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb).
“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release.
It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation.
“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.”
Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD).
In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper.
For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs.
“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.”
The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA.
A version of this article appeared on Medscape.com.
About 20% of Breast Cancer Survivors Gain Excess Weight
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ENDO 2024