Rheumatology News

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Officials at the Food and Drug Administration’s Center for Drug Evaluation and Research are taking the precautionary step of canceling or postponing advisory committee meetings and limiting staff travel in an effort to help curb the spread of the COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

“The outbreak of respiratory illness caused by a novel coronavirus, COVID-19, that started in China is spreading to other countries, including the United States,” CDER Director Janet Woodcock, MD, said in a memo to CDER staff. “As a precaution, FDA is canceling foreign official agency travel and limiting domestic travel to mission critical only, effective immediately and through April.”

Additionally, the memo notes that “CDER-organized external meetings, conferences, and workshops will be postponed or canceled from March 10 through April.”

“To mitigate the impact on our work, I encourage you to hold meetings with external stakeholders through teleconference, when possible,” she wrote.

Thus far, only a few CDER events on the FDA’s meeting webpage are listed as being canceled or postponed. Some of the affected meetings include a March 10 public meeting on patient-focused drug development for stimulant-use disorder, a March 11 meeting of the Nonprescription Drug Advisory Committee, and a March 30 public meeting on patient-focused drug development for vitiligo, all of which are postponed until further notice. The Center for Biologics Evaluation and Research also has postponed until further notice its U.S.–Japan Cellular and Gene Therapy Conference, originally scheduled for March 12.

Dr. Woodcock also noted in the memo that in relation to inspections, “we plan to use technology and established agreements with our foreign counterparts to minimize disruptions to the drug supply chain and to applications under review, so that Americans can continue to get their medications.”

gtwachtman@mdedge.com

Officials at the Food and Drug Administration’s Center for Drug Evaluation and Research are taking the precautionary step of canceling or postponing advisory committee meetings and limiting staff travel in an effort to help curb the spread of the COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

“The outbreak of respiratory illness caused by a novel coronavirus, COVID-19, that started in China is spreading to other countries, including the United States,” CDER Director Janet Woodcock, MD, said in a memo to CDER staff. “As a precaution, FDA is canceling foreign official agency travel and limiting domestic travel to mission critical only, effective immediately and through April.”

Additionally, the memo notes that “CDER-organized external meetings, conferences, and workshops will be postponed or canceled from March 10 through April.”

“To mitigate the impact on our work, I encourage you to hold meetings with external stakeholders through teleconference, when possible,” she wrote.

Thus far, only a few CDER events on the FDA’s meeting webpage are listed as being canceled or postponed. Some of the affected meetings include a March 10 public meeting on patient-focused drug development for stimulant-use disorder, a March 11 meeting of the Nonprescription Drug Advisory Committee, and a March 30 public meeting on patient-focused drug development for vitiligo, all of which are postponed until further notice. The Center for Biologics Evaluation and Research also has postponed until further notice its U.S.–Japan Cellular and Gene Therapy Conference, originally scheduled for March 12.

Dr. Woodcock also noted in the memo that in relation to inspections, “we plan to use technology and established agreements with our foreign counterparts to minimize disruptions to the drug supply chain and to applications under review, so that Americans can continue to get their medications.”

gtwachtman@mdedge.com

Officials at the Food and Drug Administration’s Center for Drug Evaluation and Research are taking the precautionary step of canceling or postponing advisory committee meetings and limiting staff travel in an effort to help curb the spread of the COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

“The outbreak of respiratory illness caused by a novel coronavirus, COVID-19, that started in China is spreading to other countries, including the United States,” CDER Director Janet Woodcock, MD, said in a memo to CDER staff. “As a precaution, FDA is canceling foreign official agency travel and limiting domestic travel to mission critical only, effective immediately and through April.”

Additionally, the memo notes that “CDER-organized external meetings, conferences, and workshops will be postponed or canceled from March 10 through April.”

“To mitigate the impact on our work, I encourage you to hold meetings with external stakeholders through teleconference, when possible,” she wrote.

Thus far, only a few CDER events on the FDA’s meeting webpage are listed as being canceled or postponed. Some of the affected meetings include a March 10 public meeting on patient-focused drug development for stimulant-use disorder, a March 11 meeting of the Nonprescription Drug Advisory Committee, and a March 30 public meeting on patient-focused drug development for vitiligo, all of which are postponed until further notice. The Center for Biologics Evaluation and Research also has postponed until further notice its U.S.–Japan Cellular and Gene Therapy Conference, originally scheduled for March 12.

Dr. Woodcock also noted in the memo that in relation to inspections, “we plan to use technology and established agreements with our foreign counterparts to minimize disruptions to the drug supply chain and to applications under review, so that Americans can continue to get their medications.”

gtwachtman@mdedge.com

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.

“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.

Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.

“It’s a good little rule of thumb,” Dr. Pope commented.

The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.

And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.

Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.

Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.

Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.

bjancin@mdedge.com

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.

“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.

“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.

“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”

Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.

“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.

In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.

“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.

Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).

Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

 

More biologics coming for nr-AxSpA

In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.

Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.

 

ACR/SAA/SPARTAN guidelines critiqued

The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.

“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.

Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.

“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.

He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.

“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.

Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.

“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.

Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

Health care factors, such as type of health system and being newly diagnosed, rather than patient socioeconomic factors, were significant predictors of smoking cessation in patients with RA, according to findings published in Arthritis Care & Research.

Smoking is a known risk factor for poor outcomes in RA, but data on factors that predict smoking cessation in these patients are limited, wrote Maria Schletzbaum, a student in the MD-PhD program at the University of Wisconsin–Madison, and colleagues. “Further, most patients with RA are not aware of the associations between smoking and RA development and complications, although such knowledge could influence cessation attempts.”

To identify predictors of smoking cessation, the investigators reviewed the 2005-2016 electronic medical records for 3,577 adults aged 18 years or older and with at least two RA diagnosis codes. The records were from two health systems, one urban and one rural.

Overall, patients who were baseline smokers and who were new to rheumatology care were 60% more likely to quit smoking (adjusted odds ratio, 1.60). However, patients who were seropositive and baseline smokers were 43% less likely to quit (aOR, 0.57). Demographic factors, including age, race, and sex, were not significantly associated with smoking cessation.

“The observed increased likelihood of quitting in patients new to rheumatology care may partially be due to cessation following a new RA diagnosis, a phenomenon previously reported in RA and other chronic diseases,” the researchers noted. Notably, the significance of being new to rheumatology disappeared in an analysis controlling for health system, “potentially suggesting greater importance of system-level factors versus individual patient factors.”

In addition, patients in the rural community health system were 66% more likely to quit smoking, possibly because about half of the patients in that system were covered by the systems’ insurance, and therefore qualified for various smoking cessation interventions, they wrote.

The study population included 915 former smokers and 507 current smokers. Seropositivity was most common in current smokers (71%), followed by former smokers (64%) and never smokers (59%). The disinclination of seropositive patients to quit smoking may reflect greater smoking intensity, and these patients may need greater support, the researchers wrote.

The study findings were limited by several factors; for example, some differences in patient populations, such as education and income levels, were not measured, and there was a lack of complete information on cumulative smoking exposure. However, the results were strengthened by the large sample size and use of data from two centers and support national guidelines for health system interventions in smoking cessation for RA patients, they noted.

The study was funded in part by the Rheumatology Research Foundation, the University of Wisconsin Medical Scientist Training Program, and the University of Wisconsin Clinical and Translational Science Award. The authors did not report any financial conflicts of interest.

SOURCE: Schletzbaum M et al. Arthritis Car Res. 2020 Mar 3. doi: 10.1002/ACR.24154.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

NATIONAL HARBOR, MD. – Stimulation of the infrapatellar branch of the saphenous nerve with an implantable electrical device is a potentially effective treatment for chronic, intractable knee pain.

In a small case series consisting of five patients with chronic knee pain, pain intensity scores on the visual analog scale (VAS) dropped from an average of 8 out of 10 before the implant to 1.4 out of 10 when measured 6 months afterward.

Pain relief was also long lasting, with an average score at 2 years still significantly reduced from baseline, at 3 out of 10 on the VAS.

“We have a lot of patients with chronic knee pain, and unfortunately, our hands are tied in terms of what we can do for them,” lead author Kwo Wei David Ho, MD, PhD, Stanford University, California, told Medscape Medical News.

“They can use NSAIDs, physical therapy, some get steroid injections, or genicular nerve blocks, but they don’t work that well. Some have knee replacement surgery, and can still have persistent knee pain after the operation, so here we are using an alternative therapy called peripheral nerve stimulation of the saphenous nerve. This provides a way to relieve pain without nerve destruction or motor dysfunction,” Ho said.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Patient Controlled

For the study, the investigators surgically implanted five patients with intractable knee pain with the StimRouter™ (Bioness, Inc).

The device takes about 15 to 30 minutes to implant, much like a pacemaker, and reduces pain by delivering gentle electrical stimulation directly to a target peripheral nerve, in this case the saphenous nerve, to interrupt the pain signal, Ho said.

“A thin, threadlike lead, or noodle, is implanted below the skin next to the target peripheral nerve responsible for the pain signal under ultrasound guidance, and then a patch or external pulse transmitter (EPT) is worn on top of the skin. This sends electric stimulation through the skin to the lead,” he explained.

The patient can then control the EPT and adjust stimulation with a wireless handheld programmer.

“Some patients turn it on at night for a couple of hours and then turn it off, some leave it on for the entire night, or the whole day if they prefer. What we’ve been noticing in our series is that after a while, patients are using less and less, and the pain gets better and better, and eventually they stop using it entirely because the pain completely resolves,” Ho said.

Good candidates for this treatment are post-knee replacement patients with residual pain, he added.

Durable Effect

Of the five patients in the case series, four had previous knee arthroplasty.

To determine the chances of a good response to the implant, study participants underwent a diagnostic saphenous nerve block, with the rationale that if the block successfully reduced knee pain by 50% or more in the short term, patients would likely respond well to the implant.

Before the peripheral nerve stimulation implant, the average pain intensity was 7.8 out of 10 on the VAS. After stimulator implantation, the average pain intensity was 1.4 at 6 months (P = .019, in 5 patients). At 1 year, the average pain intensity score was virtually the same, at 1.5 on the VAS, (P = .0032, in 4 patients). At 2 years, the average pain intensity score was 2.75 (P = .12, in 2 patients).

“This study provides preliminary evidence that stimulation at the saphenous nerve may be effective for selected patients with chronic knee pain,” Ho said.

Commenting on the findings for Medscape Medical News, Patrick Tighe, MD, MS, University of Florida, Gainesville, said that chronic knee pain continues to present “numerous diagnostic and therapeutic challenges for many patients.”

“It may be surprising, but there is still so much we don’t know about the innervation of the knee, and we are still learning about different ways to alter the behavior of those nerves,” said Tighe, who was not involved with the current study.

“This work points to some exciting opportunities to help patients suffering from chronic knee pain. We certainly need more research in this area to figure out the optimal approach to applying these findings more widely,” he said.

Ho and Tighe have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.

“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.

Several audience members were less restrained in their assessments.

“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.

Bruce Jancin/MDedge News

“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.

Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”

That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.

A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
 

In the OA pipeline

“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.

Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.

“I’m not sure this is going anywhere,” Dr. Ruderman commented.

Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.

“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.

This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.

Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)

Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.

“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.

Welcome to the wild, wild West

Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.

“It’s the wild, wild West out there,” the rheumatologist warned.

He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.

As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.

These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.

“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.

The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.

Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.

“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”


 

On a brighter note

Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.

Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.

“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”

As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.

“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.

He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.

Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.

Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

aotto@mdedge.com

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

aotto@mdedge.com