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Don’t miss early joint involvement in psoriasis
WAIKOLOA, HAWAII – advised Alan Menter, MD.
About a third of patients with psoriasis will go on to develop joint involvement, and about half of those will go on to develop permanent joint destruction “if left untreated,” he noted. But early joint involvement has to be caught first, and dermatologists aren’t doing a very good job at early detection, according to Dr. Menter, clinical professor of dermatology at the University of Texas, Dallas.
The consequences, including arthritis mutilans, can be devastating. “It’s vitally important for us to prevent any permanent joint disease by” picking it up early, he said. “Our job as dermatologists is to diagnose it early.”
It’s not hard to do, just a few extra questions and a few extra steps on the physical exam, which takes a minute or two during each visit with psoriasis patients, are needed, he said.
Dr. Menter reviewed questions to ask patients, and explained how to examine patients for joint involvement and alter treatment when it’s found, in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – advised Alan Menter, MD.
About a third of patients with psoriasis will go on to develop joint involvement, and about half of those will go on to develop permanent joint destruction “if left untreated,” he noted. But early joint involvement has to be caught first, and dermatologists aren’t doing a very good job at early detection, according to Dr. Menter, clinical professor of dermatology at the University of Texas, Dallas.
The consequences, including arthritis mutilans, can be devastating. “It’s vitally important for us to prevent any permanent joint disease by” picking it up early, he said. “Our job as dermatologists is to diagnose it early.”
It’s not hard to do, just a few extra questions and a few extra steps on the physical exam, which takes a minute or two during each visit with psoriasis patients, are needed, he said.
Dr. Menter reviewed questions to ask patients, and explained how to examine patients for joint involvement and alter treatment when it’s found, in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – advised Alan Menter, MD.
About a third of patients with psoriasis will go on to develop joint involvement, and about half of those will go on to develop permanent joint destruction “if left untreated,” he noted. But early joint involvement has to be caught first, and dermatologists aren’t doing a very good job at early detection, according to Dr. Menter, clinical professor of dermatology at the University of Texas, Dallas.
The consequences, including arthritis mutilans, can be devastating. “It’s vitally important for us to prevent any permanent joint disease by” picking it up early, he said. “Our job as dermatologists is to diagnose it early.”
It’s not hard to do, just a few extra questions and a few extra steps on the physical exam, which takes a minute or two during each visit with psoriasis patients, are needed, he said.
Dr. Menter reviewed questions to ask patients, and explained how to examine patients for joint involvement and alter treatment when it’s found, in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Biologics curb coronary artery plaques in severe psoriasis
Treatment with biologic therapy significantly improves coronary plaque profiles in patients with severe psoriasis, based on data from 121 adult patients who completed a year of follow-up.
A previous study showed a reduced rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death among individuals treated with biologic therapies, wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Md., and his colleagues.
Psoriasis “provides a reliable model to study inflammatory atherogenesis and the longitudinal impact of modulating specific cytokines on vascular behavior, while treating the primary skin disease with [Food and Drug Administration]–approved biologic therapies,” the researchers said.
In a study published in Cardiovascular Research, patients given biologics showed a 5% reduction in total coronary plaque burden after 1 year, as well as a 64% improvement in Psoriasis Area Severity Index scores. In addition, the decrease in noncalcified plaque burden in the biologics group was significantly greater, compared with the nonbiologics group (P =.03), and remained significant after controlling for standard cardiovascular risk factors.
When broken down by biologic, “we observed the greatest percent reduction of noncalcified plaque burden in patients on [anti-interleukin (IL)–17] therapy with a reduction in necrotic core suggesting a potential role for IL-17 in atherosclerotic pathways,” Dr. Elnabawi and his colleagues wrote.
(from 2.0 mg/dL to 1.4 mg/dL), but no change in the nonbiologics group.
The study population included patients naive to biologic or systemic psoriasis therapies who were assessed via clinical and laboratory data and coronary computed tomography angiography at baseline and after 1 year. A total of 89 participants with moderate to severe psoriasis received biologics, including adalimumab, etanercept, ustekinumab, secukinumab, and ixekizumab; 32 psoriasis patients received no biologics and served as a reference group. The average age of the patients was 50 years, and 58% were male. At baseline, patients had low cardiovascular risk based on Framingham scores, and moderate to severe skin disease.
The findings were limited by several factors, including the observational nature of the study, small study population, and the open-label use of biologics, as well as the use of coronary indices, rather than actual cardiovascular events, to assess cardiovascular disease risk, the researchers noted.
However, the results, combined with results from previous studies in animal models, “support further investigation of IL-17 blockade on coronary disease in humans,” they said.
The study was supported by the National Heart, Lung, and Blood Institute, with additional support from the National Institutes of Health Medical Research Scholars Program, the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, Elsevier, and other private donors. Dr. Elnabawi had no financial conflicts to disclose.
SOURCE: Elnabawi YA et al. Cardiovasc Res. 2019. doi: 10.1093/cvr/cvz009.
Treatment with biologic therapy significantly improves coronary plaque profiles in patients with severe psoriasis, based on data from 121 adult patients who completed a year of follow-up.
A previous study showed a reduced rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death among individuals treated with biologic therapies, wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Md., and his colleagues.
Psoriasis “provides a reliable model to study inflammatory atherogenesis and the longitudinal impact of modulating specific cytokines on vascular behavior, while treating the primary skin disease with [Food and Drug Administration]–approved biologic therapies,” the researchers said.
In a study published in Cardiovascular Research, patients given biologics showed a 5% reduction in total coronary plaque burden after 1 year, as well as a 64% improvement in Psoriasis Area Severity Index scores. In addition, the decrease in noncalcified plaque burden in the biologics group was significantly greater, compared with the nonbiologics group (P =.03), and remained significant after controlling for standard cardiovascular risk factors.
When broken down by biologic, “we observed the greatest percent reduction of noncalcified plaque burden in patients on [anti-interleukin (IL)–17] therapy with a reduction in necrotic core suggesting a potential role for IL-17 in atherosclerotic pathways,” Dr. Elnabawi and his colleagues wrote.
(from 2.0 mg/dL to 1.4 mg/dL), but no change in the nonbiologics group.
The study population included patients naive to biologic or systemic psoriasis therapies who were assessed via clinical and laboratory data and coronary computed tomography angiography at baseline and after 1 year. A total of 89 participants with moderate to severe psoriasis received biologics, including adalimumab, etanercept, ustekinumab, secukinumab, and ixekizumab; 32 psoriasis patients received no biologics and served as a reference group. The average age of the patients was 50 years, and 58% were male. At baseline, patients had low cardiovascular risk based on Framingham scores, and moderate to severe skin disease.
The findings were limited by several factors, including the observational nature of the study, small study population, and the open-label use of biologics, as well as the use of coronary indices, rather than actual cardiovascular events, to assess cardiovascular disease risk, the researchers noted.
However, the results, combined with results from previous studies in animal models, “support further investigation of IL-17 blockade on coronary disease in humans,” they said.
The study was supported by the National Heart, Lung, and Blood Institute, with additional support from the National Institutes of Health Medical Research Scholars Program, the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, Elsevier, and other private donors. Dr. Elnabawi had no financial conflicts to disclose.
SOURCE: Elnabawi YA et al. Cardiovasc Res. 2019. doi: 10.1093/cvr/cvz009.
Treatment with biologic therapy significantly improves coronary plaque profiles in patients with severe psoriasis, based on data from 121 adult patients who completed a year of follow-up.
A previous study showed a reduced rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death among individuals treated with biologic therapies, wrote Youssef A. Elnabawi, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Md., and his colleagues.
Psoriasis “provides a reliable model to study inflammatory atherogenesis and the longitudinal impact of modulating specific cytokines on vascular behavior, while treating the primary skin disease with [Food and Drug Administration]–approved biologic therapies,” the researchers said.
In a study published in Cardiovascular Research, patients given biologics showed a 5% reduction in total coronary plaque burden after 1 year, as well as a 64% improvement in Psoriasis Area Severity Index scores. In addition, the decrease in noncalcified plaque burden in the biologics group was significantly greater, compared with the nonbiologics group (P =.03), and remained significant after controlling for standard cardiovascular risk factors.
When broken down by biologic, “we observed the greatest percent reduction of noncalcified plaque burden in patients on [anti-interleukin (IL)–17] therapy with a reduction in necrotic core suggesting a potential role for IL-17 in atherosclerotic pathways,” Dr. Elnabawi and his colleagues wrote.
(from 2.0 mg/dL to 1.4 mg/dL), but no change in the nonbiologics group.
The study population included patients naive to biologic or systemic psoriasis therapies who were assessed via clinical and laboratory data and coronary computed tomography angiography at baseline and after 1 year. A total of 89 participants with moderate to severe psoriasis received biologics, including adalimumab, etanercept, ustekinumab, secukinumab, and ixekizumab; 32 psoriasis patients received no biologics and served as a reference group. The average age of the patients was 50 years, and 58% were male. At baseline, patients had low cardiovascular risk based on Framingham scores, and moderate to severe skin disease.
The findings were limited by several factors, including the observational nature of the study, small study population, and the open-label use of biologics, as well as the use of coronary indices, rather than actual cardiovascular events, to assess cardiovascular disease risk, the researchers noted.
However, the results, combined with results from previous studies in animal models, “support further investigation of IL-17 blockade on coronary disease in humans,” they said.
The study was supported by the National Heart, Lung, and Blood Institute, with additional support from the National Institutes of Health Medical Research Scholars Program, the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, Elsevier, and other private donors. Dr. Elnabawi had no financial conflicts to disclose.
SOURCE: Elnabawi YA et al. Cardiovasc Res. 2019. doi: 10.1093/cvr/cvz009.
FROM CARDIOVASCULAR RESEARCH
Key clinical point: Psoriasis patients treated with biologics also showed improvement in coronary artery profiles after 1 year, compared with patients not treated with biologics.
Major finding: Biologic therapy was associated with a 5% reduction in total coronary plaque burden from baseline.
Study details: The data come from 121 psoriasis patients in a prospective, observational study.
Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, with additional support from the National Institutes of Health Medical Research Scholars Program, the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, Elsevier, and other private donors. Dr. Elnabawi had no financial conflicts to disclose.
Source: Elnabawi YA et al. Cardiovasc Res. 2019. doi: 10.1093/cvr/cvz009.
Different disease features found with family history of psoriasis versus PsA
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Family histories of psoriasis and psoriatic arthritis were linked to different skin phenotypes, disease severity, and musculoskeletal features.
Major finding: Compared with no family history, psoriasis family history was a risk factor for enthesitis (odds ratio, 1.931) and younger age of onset (OR, 0.976) while psoriatic arthritis family history was linked to higher risk of deformities (OR, 2.557) and lower risk of plaque-type psoriasis (OR, 0.417).
Study details: A retrospective analysis including 1,393 Turkish or Canadian patients enrolled in a psoriatic arthritis database.
Disclosures: The study authors reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
Source: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
Psoriatic arthritis eludes early diagnosis
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Guselkumab tops secukinumab over 48 weeks for plaque psoriasis
GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.
The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.
The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.
“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”
Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).
ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.
The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.
Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.
The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.
Global Academy and this news organization are owned by the same parent company.
This article was updated 2/1/19.
GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.
The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.
The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.
“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”
Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).
ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.
The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.
Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.
The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.
Global Academy and this news organization are owned by the same parent company.
This article was updated 2/1/19.
GRAND CAYMAN, CAYMAN ISLANDS – Guselkumab bested secukinumab in a 48-week-long study of plaque psoriasis, with 84.5% of patients on the interleukin (IL)-23 blocker hitting at least a 90% improvement in their Psoriasis Area Severity Index (PASI), compared with 70% of those taking secukinumab, which blocks IL-17.
The drug was numerically, but not significantly, better than secukinumab in the PASI 75 response at weeks 12 and 48 (84.6% for guselkumab at both time points vs. 80.2% for secukinumab at both time points). This finding on the primary secondary endpoint knocked the P values of the other five into “nominally significant” ranges. But the responses were still good enough for researchers to tag guselkumab as noninferior to its competitor, Jeffrey M. Sobell, MD, said at the meeting provided by Global Academy for Medical Education.
The difference also speaks to the difference in the drugs’ onset of action and its peak efficacy, said Dr. Sobell, of the department of dermatology at Tufts University, Boston.
“In both groups, the PASI 90 increased similarly in the first month,” to about 20%, he commented. “But at week 12 and after, it was consistently higher in guselkumab, peaking around week 28. Secukinumab peaked around weeks 16 to 20 and then slowly declined.”
Despite not being statistically significant, the other secondary efficacy endpoints were certainly enough to pique the audience’s attention. At week 48, guselkumab topped secukinumab in both PASI 100 (58.2% vs. 48.4%, respectively) and Investigator’s Global Assessment (IGA) scores of 0 (62.2% vs. 50.4%) and 0-1 (85% vs. 74.9%).
ECLIPSE randomized 1,048 patients with moderate to severe plaque psoriasis to 100-mg subcutaneous guselkumab at weeks 0, 4, and 12, followed by dosing every 8 weeks, or to 300-mg subcutaneous secukinumab administered by two subcutaneous injections of 150 mg at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The primary endpoint of the study was the proportion of patients achieving a PASI 90 response at week 48. Secondary endpoints were assessed at weeks 12 and 48, with safety monitoring through week 56.
The mean baseline Body Surface Area score was 24, and the mean PASI score was 20. Patients had already been treated with phototherapy (51.8%), nonbiologic systemic medications (53.7%), and biologics (29%). About 37% were naive to both nonbiologics and biologics.
Both drugs were well tolerated, with no unanticipated adverse events. Through week 44, the discontinuation rates were 5% for guselkumab and 9% for secukinumab. Adverse events were common in both arms (77.9% and 81.6%, respectively). Serious adverse events occurred in 6.2% and 7.2%, respectively. These included serious infections in six patients taking guselkumab and five taking secukinumab. Superficial Candida infections occurred in 2% of the guselkumab group and 5.7% of the secukinumab group; Tinea infections occurred in 1.7% and 4.5%, respectively.
The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma. Secukinumab is marketed as Cosentyx.
Global Academy and this news organization are owned by the same parent company.
This article was updated 2/1/19.
REPORTING FROM THE CARIBBEAN DERMATOLOGY SYMPOSIUM
Key clinical point: Guselkumab outperformed secukinumab for patients with moderate to severe plaque psoriasis.
Major finding: PASI 90 was achieved in 84.5% of patients on guselkumab and 70% on secukinumab.
Study details: The phase 3 study randomized 1,048 patients to guselkumab or secukinumab.
Disclosures: The session was sponsored by Janssen, the manufacturer of guselkumab (Tremfya). Dr. Sobell is a consultant for Janssen and also disclosed relationships with AbbVie, Amgen, Celgene, Eli Lilly, Merck, Novartis, Regeneron, and Sun Pharma.
Comorbidities may cut effectiveness of psoriasis biologics
PARIS – in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.
The clinical importance of this finding lies in the fact that comorbidities are highly prevalent among patients with moderate to severe psoriasis. Indeed, fully 64% of the 846 participants in PSO-BIO-REAL had at least one major comorbid condition at baseline, Finn Ziegler said at the annual congress of the European Academy of Dermatology and Venereology.
“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.
The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.
Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.
The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.
Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.
During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.
The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.
Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.
The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.
The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.
SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.
PARIS – in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.
The clinical importance of this finding lies in the fact that comorbidities are highly prevalent among patients with moderate to severe psoriasis. Indeed, fully 64% of the 846 participants in PSO-BIO-REAL had at least one major comorbid condition at baseline, Finn Ziegler said at the annual congress of the European Academy of Dermatology and Venereology.
“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.
The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.
Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.
The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.
Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.
During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.
The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.
Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.
The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.
The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.
SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.
PARIS – in response to biologic therapy, according to the results of the prospective observational PSO-BIO-REAL study.
The clinical importance of this finding lies in the fact that comorbidities are highly prevalent among patients with moderate to severe psoriasis. Indeed, fully 64% of the 846 participants in PSO-BIO-REAL had at least one major comorbid condition at baseline, Finn Ziegler said at the annual congress of the European Academy of Dermatology and Venereology.
“I think this reflects a picture that has been seen in other studies,” noted Mr. Ziegler, director of global patient access at Leo Pharma in Ballerup, Denmark.
The purpose of the 12-month PSO-BIO-REAL (PSOriasis treated with BIOlogics in REAL life) study was to assess the effectiveness of a variety of biologic agents in a real-world population typical of patients encountered in routine clinical practice, as opposed to more restrictive format of often-cited randomized trials, which generally feature a lengthy list of exclusions. One-third of participants were from the United States, with the rest drawn from four Western European countries. Their mean age was 47 years, with an 18.4-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of 14.3.
Sixty percent of participants were starting treatment with a biologic agent for the first time. The other 40% had prior biologic experience. At physician discretion, 61% of enrollees were put on a tumor necrosis factor inhibitor, either etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade); 30% initiated treatment with the interleukin-12/23 inhibitor ustekinumab (Stelara); and 9% received secukinumab (Cosentyx), an interleukin-17 inhibitor.
The five most common comorbid conditions present at baseline were hypertension, present in 33.5% of participants; psoriatic arthritis (PsA), present in 28.1%; hyperlipidemia, 20.9%; diabetes, 13.9%, and depression, present in 13.7% of the psoriasis patients.
Baseline comorbidities were significantly more common among the biologic-experienced patients. For example, their prevalence of hypertension was 42%, compared with 28% in the biologic-naive group. PsA was present in 35% of the biologic-experienced and 23% of the biologic-naive patients. Nineteen percent of biologic-experienced patients had diabetes at baseline, as did 11% of the biologic-naive group.
During the 12-month study, 3.7% of patients developed a new comorbidity, the most common being anxiety, hypertension, PsA, depression, and hyperlipidemia.
The primary outcome in the study was the complete clearance rate – a PASI 100 response – at 6 months. It ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more. The results were similar at 12 months.
Conversely, an inadequate therapeutic response as defined by a PASI 50 or less at 6 months occurred in 15% of psoriasis patients with no baseline comorbidities, 27% with one, 35% with two comorbid conditions, and 28% with three or more.
The major caveat regarding this study is that the observed association between comorbid conditions and complete clearance rates doesn’t prove causality, Mr. Ziegler noted.
The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma. Mr. Ziegler is a Leo executive.
SOURCE: Ziegler F. EADV Congress, Abstract FC04.01.
REPORTING FROM THE EADV CONGRESS
Key clinical point: As the number of baseline comorbid conditions increases, the complete clearance rate in response to biologic agents for psoriasis falls.
Major finding: The complete clearance rate after 6 months of biologic therapy ranged from a high of 31% in patients with no baseline comorbid conditions to a low of 16.5% in those with three or more.
Study details: This multinational, prospective, observational, 12-month study included 846 patients initiating biologic therapy for moderate to severe psoriasis.
Disclosures: The PSO-BIO-REAL study was sponsored by Amgen, AstraZeneca, and Leo Pharma and was presented by a Leo executive.
Source: Ziegler F. EADV Congress, Abstract FC04.01.
Brodalumab raced past ustekinumab to PASI 100
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
REPORTING FROM THE EADV CONGRESS
Key clinical point: Complete clearance rates in psoriasis patients on brodalumab were similar regardless of treatment history.
Major finding: Half of brodalumab-treated patients with moderate-to-severe psoriasis experienced complete clearance at 14 weeks; it took 44 weeks in patients assigned to ustekinumab.
Study details: This was a post hoc analysis of 52-week outcomes in more than 900 participants in the phase 3 AMAGINE-2 and AMAGINE-3 randomized head-to-head comparisons of brodalumab and ustekinumab.
Disclosures: Leo Pharma funded the post hoc analysis. The presenter reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
Source: Reich K. EADV Congress, Abstract #FC03.06.
Longterm maintenance of PASI 75 responses observed with tildrakizumab
PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.
“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).
He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).
Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.
The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.
An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.
At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.
At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.
The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.
There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.
Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.
The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.
PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.
“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).
He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).
Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.
The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.
An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.
At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.
At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.
The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.
There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.
Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.
The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.
PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.
“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).
He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).
Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.
The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.
An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.
At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.
At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.
The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.
There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.
Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.
The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.
REPORTING FROM THE EADV CONGRESS
Key clinical point: Inhibition of interleukin-23 p19 via tildrakizumab pays major long-term dividends.
Major finding: Of patients with a PASI 75 response to tildrakizumab 100 mg at 6 months, 91% maintained that level of response through 148 weeks.
Study details: This was a long-term, prospective, open-label extension study of the phase 3 reSURFACE 1 and 2 trials of 1,862 psoriasis patients.
Disclosures: The reSURFACE 1 and reSURFACE 2 trials and their extension study were funded by Sun Pharma and Merck. The presenter reported receiving research grants from and serving as a consultant to those pharmaceutical companies and more than a dozen others.
CONDOR trial: Most psoriasis patients can be downshifted to reduced-dose biologics
PARIS – with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.
The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.
CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.
Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.
The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.
“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.
There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.
At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.
Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?
No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.
The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.
PARIS – with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.
The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.
CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.
Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.
The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.
“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.
There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.
At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.
Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?
No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.
The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.
PARIS – with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.
The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.
CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.
Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.
The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.
“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.
There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.
At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.
Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?
No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.
The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.
REPORTING FROM THE EADV CONGRESS
Key clinical point: An attempt at dose reduction is worthwhile in psoriasis patients well controlled on full-dose biologic therapy.
Major finding: Two-thirds of psoriasis patients maintained disease control after 12 months on reduced-dose biologic therapy.
Study details: This was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial of 111 psoriasis patients with stable low disease activity on standard-dose biologics at enrollment.
Disclosures: The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; the presenter reported having no financial conflicts of interest.
Back pain criteria perform well in patients with active axial psoriatic arthritis
A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.
The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.
Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.
Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.
The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.
The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.
By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.
The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.
Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.
“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.
These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.
Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.
SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.
A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.
The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.
Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.
Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.
The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.
The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.
By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.
The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.
Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.
“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.
These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.
Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.
SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.
A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.
The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.
Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.
Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.
The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.
The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.
By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.
The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.
Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.
“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.
These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.
Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.
SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: An inflammatory back pain screening questionnaire, developed for ankylosing spondylitis, performed well in identifying axial psoriatic arthritis in patients with active symptoms.
Major finding: The tool performed suboptimally when patients without active symptoms were included, but had good sensitivity (82%) and specificity (88%) in patients with active axial psoriatic arthritis.
Study details: A study including more than 400 patients with psoriatic arthritis.
Disclosures: The corresponding author reported competing interests related to AbbVie, Pfizer, and Celgene.
Source: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.