FORT LAUDERDALE, FLA. — An international group of dermatologists and rheumatologists has published new recommendations for the treatment of the heterogeneous manifestations of psoriatic arthritis, but they caution that randomized data remain sparse and the recommendations may change as new data emerge.
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), which has 250 members from North America, Europe, and elsewhere, performed a formal literature review for the symptoms of peripheral arthritis, skin and nail disease, axial disease, dactylitis, and enthesitis, and formulated treatment guidelines based on this systematic review and consensus opinion.
Significant challenges exist in the management of psoriatic arthritis (PsA), according to lead author Dr. Christopher T. Ritchlin. There have been few double-blind, randomized trials that have examined the efficacy of traditional agents such as sulfasalazine and cyclosporine in PsA, so there is an inadequate evidence base for the use of these drugs. There is also no evidence that the traditional agents slow radiographic progression or are effective for axial disease, dactylitis, or enthesopathy, explained Dr. Ritchlin, who is professor of medicine and director of clinical immunology, University of Rochester (N.Y.) Medical Center.
“But it's not that we know these drugs don't work—the studies simply haven't been done,” he said at a meeting sponsored by RHEUMATOLOGY NEWS and Skin Disease Education Foundation.
Particularly problematic is the paucity of data for methotrexate, with only one older double-blind randomized trial having been done, which failed to show efficacy (Arthritis Rheum. 1984;27:376–81). “But that study was underdosed and underpowered,” Dr. Ritchlin said.
Improvements in trial design in the intervening years, incorporating more useful and measurable outcomes in PsA, favor the newer biologic agents over the older disease-modifying antirheumatic drugs (DMARDs). While there have been three double-blind trials of tumor necrosis factor (TNF) inhibitors—with these drugs clearly being effective in many patients—there have been no head-to-head trials of methotrexate versus a TNF inhibitor.
GRAPPA, therefore, has attempted to fill these knowledge gaps, to provide physicians with available evidence-based information, and to help physicians in their diagnostic and therapeutic decision making (Ann. Rheum. Dis. 2008 Oct. 24 [Epub doi:10.1136/ard.2008.094946
The GRAPPA investigators noted that their efforts were hampered by a lack of validated tools. For example, they wrote that the assessment and treatment of axial manifestations of PsA are particularly challenging and that by consensus they agreed to follow guidelines of the Assessments in Ankylosing Spondylitis Working Group and adopt the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for determination of severity and response until validated measures for axial disease in PsA can be developed.
In general, the recommendations include the following:
▸ For mild peripheral arthritis, initial treatment can include nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular glucocorticoid injections, and for moderate or severe arthritis, DMARDs or TNF inhibitors may be given.
While TNF inhibitors are recommended for use in patients who have failed at least one DMARD, the recommendations also note that the patient whose prognosis is poor can be considered for a TNF agent without prior DMARD failure. Prognosis is worse in patients with polyarticular disease, an elevated erythrocyte sedimentation rate, previous medication failure, or the presence of joint damage, loss of joint function, or diminished quality of life.
Systemic corticosteroids are typically not used in PsA because of the possibility of psoriasis flare upon withdrawal.
▸ For skin disease, first-line therapies include phototherapy, methotrexate, fumaric acid esters, TNF inhibitors, efalizumab, and cyclosporine; second-line therapies include acitretin and alefacept; and third-line therapies include sulfasalazine and hydroxyurea. Nail disease can be managed with retinoids, oral psoralen plus ultraviolet A, cyclosporine, or TNF inhibitors.
▸ For mild to moderate axial disease, treatment options include NSAIDs, physiotherapy, analgesia, and injection of the sacroiliac joint. Moderate to severe involvement of the spine can be treated with TNF inhibitors.
▸ Mild dactylitis typically can be managed with NSAIDs and injected corticosteroids, but DMARDs or infliximab can be tried if symptoms are resistant.
▸ For mild enthesitis, typically of the Achilles tendon area, NSAIDs, physical therapy, and corticosteroids can be used, while moderate disease can be treated with DMARDs. Severe enthesitis may respond to a TNF inhibitor.
The guidelines also emphasized that many new treatments are in the pipeline, “which will offer new and possibly less expensive therapeutic options.”
Dr. Ritchlin also discussed larger management issues in PsA at the meeting. “The evidence is abundantly clear that psoriatic arthritis is an independent risk factor for coronary vascular disease. A lot of these patients are young, and they don't go to their primary care physicians. They come to the rheumatologists and the dermatologists,” he said.