User login
Rapid shift to adalimumab biosimilars in Denmark contrasts with U.S. experience
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
Adalimumab biosimilars are years away from entering the marketplace in the United States because of patent disputes, but they already have led to substantial discounts in Denmark, researchers wrote in JAMA Internal Medicine.
The Danish health care system switched almost entirely to adalimumab biosimilars after the patent on the original adalimumab product, Humira, expired there in October 2018. The switch to biosimilars led to an 82% decrease in costs for the medication, wrote Thomas Bo Jensen, MD, and colleagues in a research letter.
Denmark did not automatically substitute biosimilars, but the Danish Medicines Council recommended adalimumab biosimilars for all indications following Humira’s patent expiration. The recommendations “included switching patients to a biosimilar who were already well treated with the originator,” the researchers wrote.
To study the shift to adalimumab biosimilars across all indications in Denmark and calculate cost reductions, Dr. Jensen, of the department of clinical pharmacology at Copenhagen University Hospital Bispebjerg, and coinvestigators examined monthly data on drug sales from Amgros, which purchases all hospital drugs in the country.
“The proportion of adalimumab biosimilars increased from 71.6% (7,040 of 9,829 pens) in November 2018 to 95.1% (8,974 of 9,438 pens) in December 2018,” the researchers wrote. “Costs of adalimumab decreased by 82.8% from September 2018 to December 2018 (September: 8,197 pens at $5.13 million; December: 9,438 pens at $1.01 million).” The results were similar in rheumatology, dermatology, and gastroenterology.
The Food and Drug Administration has approved five adalimumab biosimilars in the United States, but “they will not enter the market until 2023 owing to patent disputes with AbbVie, the manufacturer of Humira,” wrote Jennifer D. Claytor, MD, of the department of internal medicine at University of California, San Francisco, and Walid Gellad, MD, of the division of general internal medicine at University of Pittsburgh, in an accompanying editorial.
The annual postrebate price of Humira doubled between 2013 and 2018, from $19,000 to $38,000, and these price increases may influence the price of biosimilars, “which will be priced using Humira’s price as an anchor,” Dr. Claytor and Dr. Gellad wrote.
A rapid shift to adalimumab biosimilars across the United States when they become available is “unlikely,” they wrote. Nonetheless, “some health care systems of comparable size to Denmark (e.g., the Veterans Affairs system) and others that are larger (e.g., Kaiser Permanente) ... have the ability to switch products quickly through use of formularies and a prescriber workforce. For example, Kaiser Permanente has successfully replaced Remicade (infliximab) with biosimilars in 80% of patients.”
Given the many biologics in development and increasing health care spending, “we need to take seriously the substantial savings offered by biosimilars and the feasibility, as evidenced by Denmark, of switching to biosimilars quickly once they are available on the market,” Dr. Claytor and Dr. Gellad concluded.
The research was supported by an unrestricted grant from Helsefonden. One author disclosed receiving grants from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb outside the current study. The editorial authors had no disclosures.
SOURCE: Jensen TB et al. JAMA Intern Med. 2020 Mar 30. doi: 10.1001/jamainternmed.2020.0338.
FROM JAMA INTERNAL MEDICINE
Psoriasis Therapy During the COVID-19 Pandemic: Should Patients Continue Biologics?
AAD-NPF releases first guidelines for nonbiologic treatments of psoriasis
It’s been 11 years since 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 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 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.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Secukinumab outperforms adalimumab overall for PsA
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
REPORTING FROM RWCS 2020
Specific markers detect psoriatic disease inflammation without elevated CRP
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
FROM ARTHRITIS RESEARCH & THERAPY
Psoriasis elevates cancer risk
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.
Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.
To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.
Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.
Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).
No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.
In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.
The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.
“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.
The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.
SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.
FROM JAMA DERMATOLOGY
Tildrakizumab signals safe for pregnant psoriasis patients
A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Registry data reveal temporal relationship between psoriasis symptoms and PsA onset
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
ATLANTA – Psoriasis type and patient age at presentation among patients with psoriatic arthritis predict the timing of arthritis symptom synchronicity, according to findings from the Psoriatic Arthritis Registry of Turkey International Database.
However, in those who develop arthritis symptoms first, age at onset is not predictive of psoriatic arthritis (PsA) symptom synchronicity, Umut Kalyoncu, MD, reported at the annual meeting of the American College of Rheumatology.
Of 1,631 patients from the registry, 1,251 had psoriasis first, 71 had arthritis first, and 309 had synchronous onset, which was defined as the onset of both psoriasis and arthritis symptoms within a 12-month period. The time from skin disease to PsA was 155.6 months, –67.4 months, and 1.8 months, among the groups, respectively, and the mean age at PsA onset was similar, ranging from about 41 to 42 years in those who developed arthritis first, said Dr. Kalyoncu, of the department of rheumatology at Hacettepe University, Ankara, Turkey.
However, the mean age of PsA onset among those who developed psoriasis first was 29.4 years, compared with 46.3 years in those who developed arthritis first.
“So there is a really big difference between psoriasis beginning age,” he said.
PsA types also differed by onset symptoms: Axial involvement was more common with arthritis-first onset at 38.0%, compared with 28.8% for psoriasis first and 27.8% for synchronous onset). Oligoarthritis occurred more often with arthritis-first onset (45.1% vs. 30.7% and 29.4%, respectively), and polyarthritis occurred less often with arthritis-first onset (33.8% vs. 49.4% and 47.6%, respectively), he said.
Psoriasis type also differed among the groups: Pustular skin involvement was more common in arthritis-first patients (18.3% vs. 11.9% and 16.5% of psoriasis-first and synchronous-onset patients), scalp lesions as the initial lesion were more common in psoriasis-first patients (48.3% vs. 35.2% of arthritis-first patients and 39.8% of synchronous-onset patients), and genital involvement was present more often in arthritis-first patients (12.7% vs. 6.2% and 4.9% of psoriasis-first and synchronous-onset patients).
Early-onset (type 1) psoriasis was more common in psoriasis-first patients (74% vs. 28.1% and 51.8% of arthritis-first and synchronous-onset patients), whereas late-onset (type 2) psoriasis was more common in arthritis-first patients (71.9% vs. 26.0% and 48.2% for psoriasis-first and synchronous-onset patients).
A family history of psoriasis or PsA was more common in psoriasis-first patients (35.6% vs. 26.3% and 28.2% of arthritis-first and synchronous-onset patients), Dr. Kalyoncu said.
Treatment types did not differ between the groups.
Multiple linear regression analysis for the time elapsed from psoriasis to PsA symptom synchronicity, with all other independent variables set to baseline values, showed an overall intercept interval of 66 months, but with nail involvement, family history, or plaque psoriasis, the interval was extended by 28, 24, and 20 months, respectively. However, the presence of pustular psoriasis decreased the intercept interval by 28 months.
A temporal relationship between the onset of skin psoriasis and PsA is a well-known feature of psoriatic disease, with prior studies showing that the majority of cases involve psoriasis-first onset, Dr. Kalyoncu said, adding that heterogeneity in musculoskeletal and skin involvement is also a known feature.
However, little is known about the role of genetics, he noted.
Therefore, he and his colleagues used the Psoriatic Arthritis Registry of Turkey International Database, which was established in 2014 and now also includes data from patients in Canada and Italy, to explore the associations between disease characteristics and the temporal relationship of skin and musculoskeletal disease.
Based on the findings, age at the onset of psoriasis was the main factor that determined PsA symptom synchronicity, he said.
“We know that HLA-Cw6 is important in genetic susceptibility of psoriatic arthritis, but it is important only for early-onset arthritis, not late-onset psoriasis,” Dr. Kalyoncu said. “So our results make an indirect contribution [to the understanding of] these genetic and immunochemical differences between early-onset and late-onset psoriasis, and we need further future studies about this topic.”
Dr. Kalyoncu reported having no relevant disclosures.
SOURCE: Kalyoncu U et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2854.
REPORTING FROM ACR 2019
Apremilast more likely to succeed with moderate psoriatic arthritis activity
new research suggests.
A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.
The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.
At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.
Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.
The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.
Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).
Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.
First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.
The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.
The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.
SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134
new research suggests.
A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.
The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.
At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.
Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.
The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.
Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).
Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.
First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.
The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.
The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.
SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134
new research suggests.
A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.
The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.
At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.
Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.
The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.
Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).
Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.
First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.
The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.
The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.
SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134
FROM ARTHRITIS CARE & RESEARCH
Bimekizumab elevates psoriasis therapy
MADRID – Renowned dermatologic clinical trialist Kim A. Papp, MD, PhD, is known to pick his words carefully, and the word he uses to describe the quality of life improvement documented in psoriasis patients treated with the novel investigational humanized monoclonal antibody bimekizumab is “phenomenal.”
Dr. Papp was lead investigator in the previously reported phase 2b multicenter BE ABLE 1 trial, in which 250 patients with moderate to severe chronic plaque psoriasis were randomized double-blind to various doses of bimekizumab or placebo every 4 weeks for 12 weeks (J Am Acad Dermatol. 2018 Aug;79[2]:277-86.e10. doi: 10.1016/j.jaad.2018.03.037). He was also lead investigator in the 48-week phase 2b BE ABLE 2 extension study. He presented the 60-week quality-of-life BE ABLE 2 results for the first time at the annual congress of the European Academy of Dermatology and Venereology.
“Small numbers, but the results are nonetheless very compelling,” said Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
Bimekizumab is unique in that it selectively neutralizes both interleukin-17A and -17F, two closely related proinflammatory cytokines which, when upregulated, synergize with other proinflammatory cytokines to drive psoriasis and other immune-mediated inflammatory diseases. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit only IL-17A, and brodalumab (Siliq) targets the IL-17 receptor A. The bimekizumab clinical trials program – a work in progress – aims to demonstrate that dual neutralization of IL-17A and -17F provides a more complete therapeutic approach in psoriasis, with greater efficacy and fewer safety concerns than with current biologics, the dermatologist explained.
In BE ABLE 1, the primary endpoint of at least a 90% reduction in Psoriasis Area and Severity Index (PASI90) response was achieved at week 12 in 46%-79% of patients randomized to bimekizumab in dose-dependent fashion. Those PASI90 responses were maintained with additional treatment out to week 60 in BE ABLE 2 in 80%-100% of patients.
Dr. Papp’s focus at EADV 2019 was on the quality-of-life improvement achieved in bimekizumab-treated patients, a benefit not captured by PASI scores. For this purpose, he and coinvestigators turned to the Dermatology Life Quality Index (DLQI), measured in structured fashion every 4 weeks out to week 60.
“We often forget that even though we’re looking at the patient from the outside, what’s really important is how well they respond to our treatments internally. The DLQI is not a perfect tool, but it’s the best tool we have available. It gives us a fairly good survey of the various domains that affect patients’ day-to-day living,” he said.
In BE ABLE 1, the proportion of week-12 PASI90 responders achieving a DLQI of 0 or 1 – indicative of essentially no disease impact on quality of life – increased rapidly up until week 8. At week 12, 70%-100% of the PASI90 responders in the various treatment arms had a DLQI of 0 or 1. This quality-of-life improvement, like the PASI90 response, proved durable: When the week-12 PASI90 responders were assessed at week 60 in BE ABLE 2, 76%-93% of them had a DLQI of 0 or 1.
The improvements in quality of life correlated with clinical response. BE ABLE enrollees had an average PASI score of 19 at baseline. Overall, 79% of those with an absolute PASI score of 0 at week 12 had a DLQI of 0 or 1 at that time, as did 95% of those with a PASI of 0 at week 60. A PASI of 1 was associated with a 77% likelihood of a DLQI of 0 or 1 at week 12 and an 82% rate at week 60. In contrast, patients with an absolute PASI of 2-4 at week 12 had a 46% rate of DLQI 0/1, and those with a PASI 2-4 at week 60 had a 50% chance of having a DLQI of 0/1.
Phase 3 clinical trials of bimekizumab totaling several thousand psoriasis patients are ongoing.
The BE ABLE trials were sponsored by UCB Pharma. Dr. Papp reported serving as a consultant to and/or recipient of research grants from UCB and dozens of other pharmaceutical companies.
SOURCE: Papp KA. EADV 2019 Abstract FC02.02.
MADRID – Renowned dermatologic clinical trialist Kim A. Papp, MD, PhD, is known to pick his words carefully, and the word he uses to describe the quality of life improvement documented in psoriasis patients treated with the novel investigational humanized monoclonal antibody bimekizumab is “phenomenal.”
Dr. Papp was lead investigator in the previously reported phase 2b multicenter BE ABLE 1 trial, in which 250 patients with moderate to severe chronic plaque psoriasis were randomized double-blind to various doses of bimekizumab or placebo every 4 weeks for 12 weeks (J Am Acad Dermatol. 2018 Aug;79[2]:277-86.e10. doi: 10.1016/j.jaad.2018.03.037). He was also lead investigator in the 48-week phase 2b BE ABLE 2 extension study. He presented the 60-week quality-of-life BE ABLE 2 results for the first time at the annual congress of the European Academy of Dermatology and Venereology.
“Small numbers, but the results are nonetheless very compelling,” said Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
Bimekizumab is unique in that it selectively neutralizes both interleukin-17A and -17F, two closely related proinflammatory cytokines which, when upregulated, synergize with other proinflammatory cytokines to drive psoriasis and other immune-mediated inflammatory diseases. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit only IL-17A, and brodalumab (Siliq) targets the IL-17 receptor A. The bimekizumab clinical trials program – a work in progress – aims to demonstrate that dual neutralization of IL-17A and -17F provides a more complete therapeutic approach in psoriasis, with greater efficacy and fewer safety concerns than with current biologics, the dermatologist explained.
In BE ABLE 1, the primary endpoint of at least a 90% reduction in Psoriasis Area and Severity Index (PASI90) response was achieved at week 12 in 46%-79% of patients randomized to bimekizumab in dose-dependent fashion. Those PASI90 responses were maintained with additional treatment out to week 60 in BE ABLE 2 in 80%-100% of patients.
Dr. Papp’s focus at EADV 2019 was on the quality-of-life improvement achieved in bimekizumab-treated patients, a benefit not captured by PASI scores. For this purpose, he and coinvestigators turned to the Dermatology Life Quality Index (DLQI), measured in structured fashion every 4 weeks out to week 60.
“We often forget that even though we’re looking at the patient from the outside, what’s really important is how well they respond to our treatments internally. The DLQI is not a perfect tool, but it’s the best tool we have available. It gives us a fairly good survey of the various domains that affect patients’ day-to-day living,” he said.
In BE ABLE 1, the proportion of week-12 PASI90 responders achieving a DLQI of 0 or 1 – indicative of essentially no disease impact on quality of life – increased rapidly up until week 8. At week 12, 70%-100% of the PASI90 responders in the various treatment arms had a DLQI of 0 or 1. This quality-of-life improvement, like the PASI90 response, proved durable: When the week-12 PASI90 responders were assessed at week 60 in BE ABLE 2, 76%-93% of them had a DLQI of 0 or 1.
The improvements in quality of life correlated with clinical response. BE ABLE enrollees had an average PASI score of 19 at baseline. Overall, 79% of those with an absolute PASI score of 0 at week 12 had a DLQI of 0 or 1 at that time, as did 95% of those with a PASI of 0 at week 60. A PASI of 1 was associated with a 77% likelihood of a DLQI of 0 or 1 at week 12 and an 82% rate at week 60. In contrast, patients with an absolute PASI of 2-4 at week 12 had a 46% rate of DLQI 0/1, and those with a PASI 2-4 at week 60 had a 50% chance of having a DLQI of 0/1.
Phase 3 clinical trials of bimekizumab totaling several thousand psoriasis patients are ongoing.
The BE ABLE trials were sponsored by UCB Pharma. Dr. Papp reported serving as a consultant to and/or recipient of research grants from UCB and dozens of other pharmaceutical companies.
SOURCE: Papp KA. EADV 2019 Abstract FC02.02.
MADRID – Renowned dermatologic clinical trialist Kim A. Papp, MD, PhD, is known to pick his words carefully, and the word he uses to describe the quality of life improvement documented in psoriasis patients treated with the novel investigational humanized monoclonal antibody bimekizumab is “phenomenal.”
Dr. Papp was lead investigator in the previously reported phase 2b multicenter BE ABLE 1 trial, in which 250 patients with moderate to severe chronic plaque psoriasis were randomized double-blind to various doses of bimekizumab or placebo every 4 weeks for 12 weeks (J Am Acad Dermatol. 2018 Aug;79[2]:277-86.e10. doi: 10.1016/j.jaad.2018.03.037). He was also lead investigator in the 48-week phase 2b BE ABLE 2 extension study. He presented the 60-week quality-of-life BE ABLE 2 results for the first time at the annual congress of the European Academy of Dermatology and Venereology.
“Small numbers, but the results are nonetheless very compelling,” said Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
Bimekizumab is unique in that it selectively neutralizes both interleukin-17A and -17F, two closely related proinflammatory cytokines which, when upregulated, synergize with other proinflammatory cytokines to drive psoriasis and other immune-mediated inflammatory diseases. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit only IL-17A, and brodalumab (Siliq) targets the IL-17 receptor A. The bimekizumab clinical trials program – a work in progress – aims to demonstrate that dual neutralization of IL-17A and -17F provides a more complete therapeutic approach in psoriasis, with greater efficacy and fewer safety concerns than with current biologics, the dermatologist explained.
In BE ABLE 1, the primary endpoint of at least a 90% reduction in Psoriasis Area and Severity Index (PASI90) response was achieved at week 12 in 46%-79% of patients randomized to bimekizumab in dose-dependent fashion. Those PASI90 responses were maintained with additional treatment out to week 60 in BE ABLE 2 in 80%-100% of patients.
Dr. Papp’s focus at EADV 2019 was on the quality-of-life improvement achieved in bimekizumab-treated patients, a benefit not captured by PASI scores. For this purpose, he and coinvestigators turned to the Dermatology Life Quality Index (DLQI), measured in structured fashion every 4 weeks out to week 60.
“We often forget that even though we’re looking at the patient from the outside, what’s really important is how well they respond to our treatments internally. The DLQI is not a perfect tool, but it’s the best tool we have available. It gives us a fairly good survey of the various domains that affect patients’ day-to-day living,” he said.
In BE ABLE 1, the proportion of week-12 PASI90 responders achieving a DLQI of 0 or 1 – indicative of essentially no disease impact on quality of life – increased rapidly up until week 8. At week 12, 70%-100% of the PASI90 responders in the various treatment arms had a DLQI of 0 or 1. This quality-of-life improvement, like the PASI90 response, proved durable: When the week-12 PASI90 responders were assessed at week 60 in BE ABLE 2, 76%-93% of them had a DLQI of 0 or 1.
The improvements in quality of life correlated with clinical response. BE ABLE enrollees had an average PASI score of 19 at baseline. Overall, 79% of those with an absolute PASI score of 0 at week 12 had a DLQI of 0 or 1 at that time, as did 95% of those with a PASI of 0 at week 60. A PASI of 1 was associated with a 77% likelihood of a DLQI of 0 or 1 at week 12 and an 82% rate at week 60. In contrast, patients with an absolute PASI of 2-4 at week 12 had a 46% rate of DLQI 0/1, and those with a PASI 2-4 at week 60 had a 50% chance of having a DLQI of 0/1.
Phase 3 clinical trials of bimekizumab totaling several thousand psoriasis patients are ongoing.
The BE ABLE trials were sponsored by UCB Pharma. Dr. Papp reported serving as a consultant to and/or recipient of research grants from UCB and dozens of other pharmaceutical companies.
SOURCE: Papp KA. EADV 2019 Abstract FC02.02.
REPORTING FROM THE EADV CONGRESS