PsA Trial Design Can Improve Patient Safety, Outcomes

2022 ACR-FDA SUMMIT—With numerous effective treatments now available for psoriatic arthritis (PsA), trials in this disease should look for deeper states of remission and avoid placebo-only arms, said Laura Coates, MD, PhD, consultant rheumatologist and NIHR clinician scientist, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, U.K.

Dr. Coates

Dr. Coates and co-presenter Alexis Ogdie, MD, MSCE, associate professor of medicine and epidemiology and director of the Penn Psoriatic Arthritis and Spondyloarthritis Program, Hospital of the University of Pennsylvania, Philadelphia, addressed PsA outcomes in clinical trials during the 2022 ACR-FDA Summit held virtually in May.

Inflammation, impact of disease and damage to joints/functional impairments are three areas to measure when assessing PsA, Dr. Coates said. Ultimately, the areas that are measured should be what matter most to patients, she added. Research from 2017 found that outcomes related to pain, fatigue, physical fitness and the reduction of joint damage were the most important to patients with PsA.¹

Another consideration is the use of single measures (e.g., dactylitis, nail disease) vs. composite measures, Dr. Coates said. Single measures may be the primary outcome for studies focused on single domains; composite measures allow a better estimation of full disease activity and may influence the treatment decision given overall disease burden.

For composite measures, many trials use the ACR20, ACR50 and ACR70 response criteria. Some studies still use the Disease Activity Score-28 (DAS-28), which Dr. Coates described as problematic because it does not provide an accurate disease measure for PsA.

Dr. Ogdie

Among the composite measures for PsA, Drs. Coates and Ogdie view the Minimal Disease Activity Score (MDA) as more accurate for psoriatic disease and more relevant for clinical practice. In February, the European Medicines Agency issued a letter of support for the MDA as a primary outcome measure for PsA.²

Aim High

Aiming for stricter remission criteria should be another priority for better patient outcomes, Dr. Ogdie said. She shared a patient example: A chef developed inflammatory arthritis, particularly in her hands. This ended her career. She started with 15 swollen joints and 18 tender joints. Under the ACR20 criteria, she would still have 12 swollen joints and 14 tender joints, as well as enthesitis and dactylitis. “The patient is not well [with this],” Dr. Ogdie said.

Using ACR50 or ACR70 criteria, her joint count reduces—even enough that she could theoretically return to work. However, these outcome measures cannot be directly applied to clinical practice. Other measures, such as MDA and the Disease Activity in Psoriatic Arthritis (DAPSA) score, can be applied in practice and are more meaningful.

Drs. Coates and Ogdie also expressed concerns about the ethics and value of including placebo arms in trials. Both emphasized the need to design studies with active comparator arms and measures of deeper response. In addition, phase 4 trials and longitudinal observational studies in PsA would better address safety than long-term extension studies, Dr. Coates said.

Vanessa Caceres is a medical writer in Bradenton, Fla.

References

1. Orbai A-M, de Wit M, Mease P, et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann Rheum Dis. 2017 Apr;76(4):673–680.
2. European Medicines Agency. Letter of support for Minimal Disease Activity Score as primary outcome instrument for clinical studies in psoriatic arthritis. 2022 Feb 22. https://www.ema.europa.eu/en/documents/other/letter-support-minimal-disease-activity-score-mda-primary-outcome-instrument-clinical-studies_en.pdf.