Summary
Psoriatic arthritis (PsA) is a serious and progressive disease associated with significant morbidity and mortality. Defining outcome measures in PsA has been challenging because of the wide spectrum of clinical presentation, perceived low prevalence, and relapsing/remitting cycle. None of the current methods for defining outcome have been validated in PsA patients.
- arthritis
Psoriatic arthritis (PsA) is a serious and progressive disease associated with significant morbidity and mortality. Seventeen percent (17%) of PsA patients have ≥ 5 deformed joints, 40% to 50% deforming arthritis, 20% to 40% spinal involvement, and 11% to 19% are disabled. Defining outcome measures in PsA has been challenging because of the wide spectrum of clinical presentation, perceived low prevalence, and relapsing/remitting cycle. None of the current methods for defining outcome have been validated in PsA patients.
Beginning with Moll and Wright, several attempts have been made to develop a standard set of criteria to differentiate PsA. Recently, domains for the assessment of PsA were identified by the ClASsification of Psoriatic ARthritis (CASPAR) (Ann Rheum Dis. 2005;64:113–118) group and further refined through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) (Ann Rheum Dis. 2005;64:111–112). The following were identified as important in the assessment of patients with PsA: inflammation (peripheral joints, axial skeleton, physician global assessment), other features (dactylitis, enthesitis), skin and nails, imaging, biomarkers, and patient derived indices (pain, quality of life, itch, function). These are being further refined and instruments to measure individual items are being developed.
What can imaging tell us about PsA? MRI's ability to assess both detailed changes in bone structure and synovial inflammation, combined with its multiplanar capability, makes it a potentially valuable tool for assessing patients with PsA. Possible uses include: diagnosis and classification; early assessment of bony erosions (to define patients who already have articular structural damage); quantification of primary site synovial inflammation (potentially allowing prediction of further erosions and disease progression); simultaneous assessment of synovitis and joint erosion; and long-term evaluation of treatment outcome.
Most of the clinical trials that have evaluated the efficacy and safety of DMARDs in PsA have been small, had high placebo response rates and, particularly in the case of MTX, were underpowered to assess clinical benefit. In one of the larger trials conducted with sulfasalazine (SSZ), in which 221 PsA patients were followed over 36 weeks, significantly more patients in the SSZ group achieved PsARC (57.8% vs 44.6%; p=0.05, SSZ vs placebo, respectively). SSZ patients also showed a significant (p<0.001) decrease in ESR (Arthritis Rheum. 1996; 39:2013–20). Results from a 24-week double-blind RCT studying the safety and efficacy of leflunomide in the treatment of 139 patients with PsA were published in 2004 (Arthritis Rheum. 2004; 50:1939–50). In this study, significantly more patients in the leflunomide group achieved PsARC compared with the placebo group (59% vs 30%, p<0.0001, leflunomide and placebo respectively). ACR 20 was achieved in 36% of leflunomide-treated vs 20% of placebo-treated patients. PASI 50 and 75 scores (a score to assess improvement in cutaneous involvement) were also significantly improved in the leflunomide group (30% vs 19%; p=0.003 and 17% vs 8%; p=0.048, PASI 50 and 75, leflunomide and placebo, respectively).
Several biologic agents have been studied in PsA including alefacept, which targets the inhibition of T-cell activation and migration, IL-1ra (anakinra), which targets immune deviation, as well as etanercept, infliximab, and adalimumab, which block the activity of inflammatory cytokines. Additional trials, in patients with PsA, with these compounds singly and in combination are needed. Future therapies include IL-15, IL-6, abatacept, rituximab, anti-angiogenesis, FVIII therapies, and B-cell blockade. Investigations should be undertaken to determine whether genetics could assist in determining the most appropriate therapy.
- © 2006 MD Conference Express