Stakeholders working to fill gaps in psoriasis research

Mark Lebwohl, MD: ‘We don't have a serologic marker that predicts psoriatic arthritis or its severity. We need one.'

Mark Lebwohl, MD: ‘We don’t have a serologic marker that predicts psoriatic arthritis or its severity. We need one.’

Psoriasis patients, clinicians, and payers all need better outcomes. Getting to better outcomes doesn’t necessarily mean better drugs, said Alice Gottlieb, MD, PhD, chair and Harvey B. Ansell professor of dermatology at Tufts University School of Medicine. Getting to better outcomes means better patient-centered measures to enhance research and treatment.

Dr. Gottlieb was course director for “Research Gaps in Psoriasis: Opportunities for Future Studies and Development of New Outcomes Measures for Clinical Trials” presented Friday.

“Our current outcomes measures may not be helpful in distinguishing which drugs or doctors add extra value,” she said in an interview about the session. “Too often, psoriasis is viewed by payers and regulators as largely a cosmetic problem not of equal severity as, for example, rheumatologic disorders. In part, this is due to outcomes measures that do not take into account all aspects of psoriatic disease.”

Too many payers are making too many decisions on physician and drug quality based on claims databases in community practice, Dr. Gottlieb explained. These databases do not assess either patient severity or disease. There is not even a measure for disease clearance.

Only 55 percent of psoriasis patients are treated to the level of their severity and 59 percent report psoriasis to be a problem in everyday life. Not surprisingly, only 48 percent of psoriasis patients are satisfied with their current treatment.

“Our idea of clearance does not align with current measures by not taking into account such items as location, type, or comorbid conditions, and how we perceive severity,” said Courtney Schneider, director of strategic alliances at the National Psoriasis Foundation. “Clinical trial measures do not translate into a clinical practice setting and current measures do not help us when comparing potential treatments. We want to share our patient perspectives on outcomes to show the impact and the need for standard measures to help activate change to the health care system.”

Dr. Gottlieb pointed to the International Dermatology Outcome Measures Initiative (IDEOM), of which she is board chair. IDEOM’s mission is to establish validated and standardized patient-centered outcome measures that can be used in both clinical research and clinical practice.

IDEOM uses an onion strategy developed by OMERACT, the Outcome Measures in Rheumatoid Arthritis Clinical Trials group. Core measures must be included in every trial. Successive layers include measures that are applied more selectively. The outermost layer is the research agenda.

Key Research Gaps

While there has been dramatic success in treating psoriasis, gaps remain. Key questions include the ability to predict who will develop psoriatic arthritis and the ability to prevent them; the ability to predict cardiac, renal, and other comorbidities, and the ability to prevent them; and the ability to predict which patients will respond to which therapies.

“When you ask if we can predict who will develop psoriatic arthritis, you are really asking if we can treat to prevent joint disease,” said Mark Lebwohl, MD, Sol and Clara Kest professor and chair of dermatology, Icahn School of Medicine at Mount Sinai Hospital, New York. “We should be able to.”

Population studies show that 72 percent of psoriatic arthritis patients had an initial onset of psoriasis. Seven percent reported concurrent onset and 21 percent reported an initial onset of arthritis. Imaging studies using MRI found that 68 percent of psoriasis patients had joint involvement with at least one arthritic sign. Joint damage was seen before patients had clinical evidence of joint symptoms and X-ray imaging found only 32 percent of joint damage.

Etanercept, adalimumab and other biologics can produce radiographic improvement in psoriatic arthritis, Dr. Lebwohl said, but only if the agents are used.

“We don’t have a serologic marker that predicts psoriatic arthritis or its severity,” he said. “We need one.”

Treating to Target

Psoriasis non-treatment, under-treatment, and treatment dissatisfaction remain a significant problem in the United States. Treat-to-target offers a potential solution.

“The hypothesis is that patients do better if you aim for a high target and you alter your treatments until you reach that target,” said Joel Gelfand, MD, MSCE, medical director, clinical studies unit, associate professor of dermatology and epidemiology, and senior scholar at the Center for Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine. “We have this in rheumatoid arthritis, and it is being developed in psoriatic arthritis.”

TICOPA, the TIght COntrol of Psoriatic Arthritis study, compared treat-to-target against standard of care. Patients who were treated to target had better outcomes than those who received the current standard of care, Dr. Gelfand said.

“I am for a certain outcome —clearance — and I will change my treatments until we get to that point,” he said.

Building the Outcome Onion

Setting a clear target, such as clear skin, seems like a simple task, but the reality is far more complex. Multiple stakeholders in psoriasis — patients, clinicians, researchers, and payers — all have their own goals, priorities, and questions of interest. Creating outcome measures that satisfy all of the stakeholders can be a time-consuming process.

“The process by which you set outcome measures must be inclusive, it must be iterative and it must be transparent,” said April Armstrong, MD, MPH, vice chair of clinical research, associate professor of dermatology, director of dermatology clinical trials and outcomes research, and director of the psoriasis program at the University of Colorado. She is a dermatologist member of the IDEOM Element Distillation Group. The group has five dermatologists, four patients, a biostatistician, and two OMERACT advisors.

“You need agreement on the core areas that need to be measured to assess the effects of an intervention,” Dr. Armstrong said. “You need to define domains and subdomains within the core areas, the component areas, concepts and specifications you are going to measure or assess. You need agreement on outcomes, the identifiable results in a domain or subdomain that result from exposure to a causal factor or a health intervention. You need common measurement instruments, the tools to measure a quality or quantity of a variable. And you need outcomes measurement instruments, the instruments used to assess specific outcomes.”

Delphi Process

IDEOM is using a Delphi consensus process developed by OMERACT to determine an initial set of core outcome measurements for clinical trials in psoriasis. The core set is an agreed upon, standardized set of outcomes that should be measured and reported as a minimum in all clinical trials.

“Core outcome sets are much more likely to measure appropriate outcomes,” said Robin Christensen, PhD, professor of clinical epidemiology and head of the musculoskeletal statistics unit at The Parker Institute. “Using core outcome sets increases consistency across trials, maximizes the potential for trials to contribute to systematic reviews of key outcomes such as PASI75 in psoriasis, and reduces selective reporting by trialists who ‘forget’ to publish negative results within the trial.”

Stakeholders must agree on what to measure in at least one domain for four core areas —death, life impact, resource use, and pathophysiological manifestations. The next step is agreement on how to measure and identifying at least one applicable instrument for each domain.

The final core set for psoriasis contains one domain from each of the core areas —peripheral joint activity, skin activity, patient global pain, physical function, and health related quality of life. A second layer includes other domains that may be important depending on the study question, including dactylitis, enthesitis, spinal, fatigue, radiology, and acute-phase reactants. An outer layer includes domains of research interest, including MRI, CT, ultrasound, tissue analysis, and participation.

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