Psoriatic arthritis: Treatment of patients with PsA

PsA, an inflammatory arthropathy, may be associated with psoriasis in up to 42% of patients. Most common estimates, however, suggest that approximately 25% to 30% of patients with psoriasis will develop PsA usually 5 to 12 years after the onset of their skin disease.163 Left untreated, a proportion (up to 50%) of patients with PsA may develop persistent inflammation with progressive joint damage that can lead to severe physical limitations and disability. For this reason, early diagnosis of PsA is critical. Dermatologists are in an excellent position to make the early diagnosis of and treat PsA appropriately, and thus should actively elicit signs and symptoms of PsA at every patient visit. If PsA is diagnosed, treatment should be initiated to alleviate the signs and symptoms of PsA, inhibit structural damage, and maximize quality of life. Dermatologists uncomfortable or untrained in evaluating or treating patients with PsA should refer to rheumatologists. Preferably, close cooperation between dermatologists and rheumatologists will offer optimal benefit to patients with both psoriasis and PsA. 

View Case 7: Psoriatic arthritis

Conclusion: Approach to patients with PsA 

Mild PsA is most often managed with NSAIDs alone. If the PsA is unresponsive after 2 to 3 months of therapy with NSAIDs, treatment with MTX should be considered. For patients with moderate to severe PsA; MTX, TNF-alfa blockade, or the combination of these therapies is considered first-line treatment.5 The data supporting the use of monotherapy with MTX in PsA are based on only two small randomized placebo-controlled studies.5 However, MTX is often used as a first-line therapy before TNF-alfa blockade treatment, largely because of its significantly lower cost. The combination of orally administered MTX and cyclosporine can also be effective in the treatment of PsA. In a 12-month, randomized, multicenter, double-blind, placebo-controlled trial combining oral cyclosporine with oral MTX in patients with PsA who had a prior incomplete response to MTX monotherapy, there was a significant improvement in the swollen joint count and C-reactive protein levels in the combination MTX-cyclosporine arm when compared with baseline, but not in the MTX-placebo group when compared with baseline.187

At the primary end point and at the marketed dosages, all 4 TNF-alfa inhibitors show similar efficacy for the signs and symptoms of PsA. There are, however, observed differences in the efficacy of these agents for the treatment of cutaneous psoriasis. Infliximab clears cutaneous psoriasis in the highest proportion of patients and with the greatest rapidity, followed by adalimumab and then etanercept. It is important to note that in all of the TNF-alfa inhibitor studies of patients with PsA, between 40% and 50% of patients were taking concomitant MTX along with the TNF-alfa inhibitor under evaluation. Golimumab, the most recently approved TNF-alfa inhibitor, has not been tested as monotherapy in patients with moderate to severe psoriasis who do not have PsA. Evaluations of PASI scores in PsA studies have shown that on average the initial PASI score at the beginning of these studies is below 10, making evaluation of PASI-75 response through the course of the study difficult to interpret statistically. Ustekinumab has shown efficacy against the signs and symptoms of PsA in a recently published small phase II clinical trial. In this study, 42% of the 76 ustekinumab-treated patients achieved an American College of Rheumatology 20 response at week 12 compared with 14% of the 70 placebo-treated patients.188 This is somewhat inferior to what has previously been seen in pivotal studies of all 4 TNF-alfa inhibitors for the treatment of PsA.5 Until the results of the phase III trials of ustekinumab for PsA become available, the TNF-alfa inhibitors should be considered the biologic class of choice for these patients.

Although MTX is far less expensive than the TNF-alfa inhibitors, only recently have there been prospective, randomized, adequately powered clinical trials comparing MTX with the TNF-alfa inhibitors in PsA. In one trial, treatment with 15 mg a week of oral MTX did not prevent radiologic progression of PsA, whereas in another trial, increasing the weekly MTX dosage to 25 mg did appear to reduce radiologic progression of PsA.189 All of the TNF-alfa inhibitors appear to diminish the likelihood of radiographic progression of PsA compared with MTX, but these findings are derived from comparing several different studies rather than one large comparator study.190 Well-controlled clinical studies are therefore needed to directly compare these agents. Adding low-dose MTX to one of the TNF-alfa inhibitors leads to further improvement in PsA joint responses. Because of the lack of sufficient data, however, it is difficult for the clinician to make definitive recommendations regarding the proper sequence or duration of therapies that should be used to treat patients with moderate to severe PsA.

We would suggest however that, in general, it is appropriate to initiate MTX treatment for patients with moderate to severe PsA who have no contraindications to MTX therapy. If after 12 to 16 weeks of MTX therapy with appropriate dose escalation there is minimal improvement in the signs and symptoms of PsA, it is very appropriate to either add or switch to a TNF-alfa inhibitor, with all of the TNF-alfa inhibitors being equally reasonable choices.

References

  1. Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol 2008;58:851-64.
  2. Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010;362:118-28.
  3. Fraser AD, van Kuijk AW, Westhovens R, Karim Z, Wakefield R, Gerards AH et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann Rheum Dis 2005;64:859-64.
  4. Gottlieb A, Menter A, Mendelsohn A, Shen YK, Li S, Guzzo C et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet 2009;373:633-40.
  5. Heiberg MS, Kaufmann C, Rodevand E, Mikkelsen K, Koldingsnes W, Mowinckel P et al. The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study. Ann Rheum Dis 2007;66:1038-42.
  6. Gladman DD, Mease PJ, Choy EH, Ritchlin CT, Perdok RJ , Sasso EH. Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT. Arthritis Res Ther 2010;12:R113.

Navigate section 6 of the psoriasis guideline: Case-based review

Citation note

Menter A, Korman NJ, Elmets CA,Feldman SR, Gelfand JM, Gordon KB, Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011 Jul;65(1):137-74. 



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