A biomarker panel that simultaneously measures the expression of 57 synovial tissue proteins could be used to predict which patients with psoriatic arthritis (PsA) would respond to tumor necrosis factor (TNF) α inhibitors or T-cell inhibitors, researchers report in an article published online September 3 in the Annals of the Rheumatic Diseases.
Opeyemi S. Ademowo, PhD, and colleagues from University College Dublin, Ireland, and from the University of Amsterdam, the Netherlands, note that about 30% of patients with PsA do not benefit from TNF inhibitors and that better selection might protect such patients from potential adverse effects and the high cost for drugs when they are unlikely to be effective.
"This panel may help to identify patients that will likely benefit from treatment including TNF-α inhibition and T-cell modulation, help monitor treatment and support the design of personalised treatment for patients," the authors write.
Not everyone, however, is convinced that the panel is practical. Dafna D. Gladman, MD, FRCPC, professor of medicine at the University of Toronto and senior scientist at the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Ontario, Canada, told Medscape Medical News, "Generally one would prefer to use serum, which is more accessible to everyone than synovial tissue. However, it makes sense to start with this type of study in the tissue which is mostly affected by the disease. Whether the findings in the synovial tissue are reflected in proteins in the serum needs to investigated, and I imagine that the authors will be doing that. They also have some other proteins to test as well."
Dr. Gladman, who was not involved in the study, added, "This is still far away from clinical practice. It is a cumbersome procedure which is only available in expert laboratories. One would want to then develop simple methods, such as [enzyme-linked immunosorbent assay,] to identify these proteins in the serum before making it available for clinical use."
Dr. Ademowo and colleagues examined the differential expression of proteins from synovial tissue from patients with PsA who were either good responders or nonresponders to biological therapy (adalimumab). The patients were already participating in a study examining changes in synovial tissue associated with adalimumab treatment. They had been randomly assigned to adalimumab (40 mg subcutaneously) or placebo on day 1 and day 15; all participants had then received adalimumab 40 mg/week and were followed for 12 weeks. Response was classified according to the disease activity score in 28 joints (DAS28). Responders had an improvement in DAS28-C-reactive protein higher than 1.2, with a final DAS28-C-reactive protein score of 3.2 or less.
In the discovery phase, the authors analyzed proteins from baseline synovial tissue samples from 5 responders and 5 nonresponders. They selected potentially useful markers that differed between responders and nonresponders.
The candidate biomarker panel that emerged from this discovery phase was confirmed using the 18 (of 20) available baseline samples from the adalimumab-treated patients, and panel readings correlated well with clinical endpoints.
To further validate the panel's use, the researchers used the candidate panel to predict response in 7 patients with active PsA who were enrolled in a clinical trial of abatacept and for whom baseline synovial tissue samples and follow-up data were available. The panel correctly predicted the 3 patients who had good responses at 6 months, as well as the 3 nonresponders. One patient predicted to have a good response was a moderate responder at 6 months.
"To date, the findings have not been confirmed in more readily available biological fluids (serum or synovial fluid). This clearly would be the ultimate goal of this work as synovial biopsies are more invasive," the authors write.
Dr. Gladman's group has been working on serum biomarkers that distinguish patients with PsA from those with psoriasis alone, as well as biomarkers to identify response to anti-TNF agents.
The authors did not respond to requests by Medscape Medical News for comment.
This project was supported by the Department of Rheumatology at St. Vincent’s University Hospital, Dublin, Ireland. The University College Dublin Conway Institute is funded by the Programme for Research in Third Level Institutions, as administered by the Higher Education Authority of Ireland. The authors and Dr. Gladman have disclosed no relevant financial relationships.
Ann Rheum Dis. Published online September 3, 2014. Abstract
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Cite this: Psoriatic Arthritis: Biomarkers May Predict Drug Response - Medscape - Sep 15, 2014.
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