Methotrexate is widely prescribed for the treatment of psoriatic arthritis, yet its role remains controversial and unsupported by persuasive evidence. The British MIPA (Methotrexate in Psoriatic Arthritis) trial concluded that methotrexate wasn’t superior to placebo, and hence can’t be considered a DMARD in PsA (Rheumatology [Oxford] 2012 Feb. 17 [epub ahead of print]). Design limitations rendered MIPA a less-than-definitive study; however, it’s unlikely any further placebo-controlled trials of methotrexate in PsA will be carried out, in Dr. Ritchlin’s view.
"The role of methotrexate remains to be determined, but it’s not looking good at this point," he observed.
Rheumatologists with RA patients on methotrexate typically monitor them for hepatic fibrosis via liver function tests rather than liver biopsy. However, Dr. Ritchlin believes that more-invasive monitoring is warranted in psoriatic arthritis patients with type 2 diabetes, obesity, or both, as these have been shown to be risk factors for accelerated liver fibrosis in psoriasis patients on methotrexate (J. Hepatol. 2007;46:1111-8).
"When I have a patient with psoriatic arthritis, and we’re going to use methotrexate, and they have type 2 diabetes or are obese, I tell them about that study, in which investigators did biopsies and showed that these two risk factors, alone or together, identify rapid progressors in terms of fibrosis. I tell those patients they should have liver biopsies at 2-g intervals. And most of those patients will elect to use another therapy when I tell them that. But I think it’s important to enlighten them" on those data, Dr. Ritchlin said.
On the therapeutic horizon – in addition to the studies of IL-17 inhibition – is a phase III clinical trial of apremilast in the treatment of PsA, which has been completed and submitted for publication following a successful placebo-controlled, phase II study of the investigational novel oral phosphodiesterase-4 inhibitor.
"This drug has a very low side-effect profile," Dr. Ritchlin commented.
Promising new targets in psoriatic arthritis that have yet to be explored include RANKL (receptor-activated nuclear factor–kappaB ligand) and the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway.
The TNF inhibitors are the best established agents today for treatment of PsA. In phase III trials, all of the TNF inhibitors showed similar efficacy for the joint disease, whereas the skin response was better with the antibody agents.
Dr. Ritchlin said he is asked all the time about what to do for PsA patients who are TNF-inhibitor nonresponders. His strategy is first to focus on treating the site of the flare; for example, if it’s a skin flare, he works with a dermatologist, who may address the skin lesions with phototherapy or topical agents.
Next, he considers switching to a different TNF inhibitor or adding or switching a conventional DMARD. "A switch to leflunomide (Arava) can be very effective in this population, especially for joint flares," the rheumatologist continued.
If the patient’s response is still inadequate, Dr. Ritchlin switches from a TNF inhibitor to ustekinumab on the strength of a favorable phase II study (Lancet 2009;373:633-40).
Dr. Ritchlin reported serving as a consultant to Abbott, Amgen, Centocor, UCB, Wyeth, Genentech, and Targacept, as well as receiving research funding from multiple sources.