Psoriatic arthritis trials should seek deeper remission states, end placebo controls
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Clinical trials for psoriatic arthritis therapies should place a greater focus on using deeper states of remission as primary and co-primary endpoints, according to speakers at the FDA & American College of Rheumatology Virtual Summit.
Additionally, study designers should discontinue the use of placebo-only control arms, Laura Coates, MBChB, MRCP, PhD, of the University of Oxford, and Alexis Ogdie, MD, of the University of Pennsylvania Perelman Center for Advanced Medicine, told attendees.
“Many people come into these trials on methotrexate, let’s say, but they still have very high disease activity such that they can get into these trials,” Ogdie said. “Continuing them on that therapy alone, we suggest, is not ethical.”
In lieu of placebo-control arms, Ogdie and Coates suggested the use of active-comparator studies to look at the effects of one active drug compared with another.
“If we do move to a more active-comparator design, then we can think about measures of deeper response,” Coates said.
Looking at measuring patient improvement, it is important to consider the metrics that matter to the patient, and the attainable degrees of improvement, when crafting trial endpoints, the speakers said.
Using a patient with 15 swollen joints and 18 tender joints at baseline as an example, an ACR20 response is not substantial enough to constitute defining the patient as “well,” Ogdie argued.
“At the end of, let’s say, a 12-week treatment period, she achieves an ACR20 response, she can achieve that response and have a swollen joint count of 12 and a tender joint count of 14,” Ogdie said. “This patient is not ‘well’ — this is not a good benchmark. This patient does not come back happy with her progress.”
In addition to advocating for higher standards in disease improvements, the speakers noted the importance the rate of improvement plays in patients with PsA.
“This is another thing to consider as we design the trials of the future — that we’re considering also how long it takes to get to improvement, and sustain that improvement, as opposed to single-timepoint analyses,” Ogdie said.
She added: “We want to emphasize that we think that the ACR20 should be reconsidered as a primary outcome measure in these trials, and we should be thinking about other targets, such as [minimal disease activity] as a primary outcome.”
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Coates L, et al. Outcome measures psoriatic arthritis. Presented at: The FDA & American College of Rheumatology Virtual Summit; May 17-18, 2022.
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