Efforts underway to tailor psoriatic arthritis treatments to the various tissues involved in the pathogenesis of the disease could optimize therapeutic approaches, Dr. Iain McInnes said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
“Psoriatic arthritis [PsA] is a disease whose treatment is evolving quickly, ” added Dr. McInnes, professor of medicine and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland). “We have new ideas about pathogenesis, emerging studies that inform the best strategic approach to disease management, including potential value in a treat-to-target approach, and new therapeutics that offer a range of options to allow us to optimize treatment.”
Dr. Iain McInnes
He pointed to recent evidence for a diverse pathogenesis of PsA subtypes. Synovial membranes in PsA have high levels of tumor necrosis factor (TNF)-alpha, while resident populations of interleukin (IL)-23 receptor–positive T cells are found in entheses and IL-17 is abundant in psoriatic lesions. Genome-wide association studies have underscored the role of the IL-23 and IL-17 cytokine axis, while other work has implicated Th17 cytokines in mesenchymal tissue changes.
Although drug development efforts have typically viewed rheumatoid arthritis and PsA as homogeneous, “we can appreciate the extent of articular, entheseal, and cutaneous involvement, and look to tailor therapies accordingly,” Dr. McInnes said.
So what will the next decade look like for PsA? Therapy will center around TNF-alpha inhibitors, new cytokine pathways, and small-molecule inhibitors, according to Dr. McInnes. While anti-TNF agents are not universally tolerated or effective, their “well-established safety profile” and positive effects on American College of Rheumatology response criteria and radiographic endpoints generally outweigh risks of infection and problems with decreasing long-term drug survival, he said. These agents also can improve disease activity, skin symptoms, physical function, fatigue, overall quality of life, enthesitis, and dactylitis, he noted.
Other recent additions to the PsA arsenal include the IL-12/IL-23 inhibitor ustekinumab (Stelara), which in the PSUMMIT 1 and 2 trials was associated with decreased rates of radiographic progression and dose-dependent improvements in enthesitis, Dr. McInnes said. The phosphodiesterase-4 inhibitor apremilast (Otezla) was associated with significantly better ACR 20 response at week 16 and significantly greater improvements in Maastricht Ankylosing Spondylitis Enthesis Score and measures of dactylitis at week 24 of the PALACE trials. Most recently, in the FUTURE1 and FUTURE2 trials, the IL-17A inhibitor secukinumab (Cosentyx) beat placebo in terms of ACR 20, ACR 50, ACR 70, resolution of dactylitis and enthesitis, and radiographic measures of disease progression.
The availability of effective biologics raises the possibility of a treat-to-target approach geared toward clinical remission or low disease activity, Dr. McInnes concluded. “Targets for low disease activity in PsA are now available. Composite measures of disease activity, such as minimal disease activity (MDA), encompass all clinically important aspects of PsA,” he emphasized. While studies still need to pinpoint the best therapeutic pathways for disease subtypes, the first treat-to-target study of PsA found that tailoring therapy based on remission or minimal disease activity led to significantly better ACR 20, ACR 50, and ACR 70 responses at week 48, compared with standard care, he noted.
Dr. McInnes reported receiving research funding or honoraria from Novartis, Janssen, AbbVie, UCB, Pfizer, and MSD Pharmaceuticals, all of which make medications for rheumatic diseases. Global Academy for Medical Education and this news organization are owned by the same parent company.