BOSTON — Rheumatologists must rethink their reflex to prescribe methotrexate for psoriatic arthritis, given data showing anti-tumor necrosis factor agents are more effective for this indication, Dr. Christopher Ritchlin said at a rheumatology conference sponsored by Harvard Medical School.
“About 70%-80% of clinicians around the world who treat psoriatic arthritis say methotrexate is the first drug that they use, yet the only double-blind randomized controlled trial addressing the question was too underpowered and underdosed to make any conclusions regarding efficacy,” he added.
Another concern is liver toxicity with methotrexate, since psoriasis patients tend to have higher alcoholism rates. And there is evidence of progression of fibrosis in psoriatic arthritis patients on methotrexate, said Dr. Ritchlin, of the University of Rochester, N.Y. Also, unlike rheumatoid arthritis, there is no evidence that methotrexate is synergistic with other disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis.
In contrast, the production of TNF-α has been shown to play a central role in the development of psoriasis and psoriatic arthritis by sustaining the inflammatory process in the skin and the joints, and anti-TNF-α agents appear to effectively block that activity, said Dr. Ritchlin. Dr. Marte Schrumpf Heiberg of Diakonhjemmet Hospital, Oslo, has reported data from 526 patients with psoriatic arthritis. After 6 months, patients on anti-TNF-α treatment demonstrated significantly greater clinical improvement in disease measures, versus those on methotrexate monotherapy (Ann. Rheum. Dis. 2007;66:1038–42).
And Dr. Filip van den Bosch of University Hospital, in Gent (Belgium), and colleagues presented data showing adalimumab in 414 patients with psoriatic arthritis resulted in clinically meaningful joint and skin improvements at 12 weeks and was well tolerated. In a separate study, the researchers linked adalimumab with clinically important gains in psoriatic nail disease.
Anti-TNF-α therapy also seems to impact the enthesopathic pathology of psoriatic arthritis. Dr. Helena Marzo-Ortega of Chapel Allerton Hospital in Leeds (England), and colleagues have shown infliximab is tied to improvements in MRI-determined bone edema in psoriatic arthritis (Ann. Rheum. Dis. 2007;66:778–81).
Other potential therapeutic targets for psoriatic arthritis include B cells and T cells, as well as the interleukin-23/Th17 pathway, which is directly tied to psoriasis. Anti-p40 therapy targets an interleukin-23 subunit.
“Psoriatic arthritis, unlike rheumatoid arthritis, is quite complex in its disease manifestation,” Dr. Ritchlin. “Traditionally, psoriatic arthritis was defined as an inflammatory arthritis associated with psoriasis. More and more, however, it has become clear that psoriasis is a systemic disease.”
Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible, said Dr Ritchlin.
Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible. DR. RITCHLIN