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Objectives: Disease-modifying antirheumatic drugs (DMARDs) are frequently prescribed as a first step therapy in active psoriatic arthritis (PsA). However, evidence is sparse and scattered. The objective of this study is to evaluate the efficacy and safety of DMARDs in PsA., Methods: We performed a systematic review based on electronic searches through Medline, Cochrane Central and Embase (from July 1980-2010) for randomised control trials (RCTs) in PsA. Outcome measures were those included in the core-set from Outcome Measures in Rheumatology Clinical Trials (OMERACT) and adverse effects., Results: A preliminary search identified 3781 potentially relevant RCTs, while only 11 fulfilled inclusion criteria. Ten studies had a parallel design and, one was a cross-over trial. Quality reached a Jadad score over 3 in 6/11 (54.6%). We observed evidence of a moderate improvement of pain and reduction of ESR with DMARDs. The global risk of withdrawals due to adverse events was 2.41 [95% confidence interval (CI) 1.53, 3.82]. The risk of GI adverse effects (nausea, vomiting, abdominal pain, diarrhoea and/or oral ulcers) was 2.02 [95% CI 1.34, 3.03] and of headache was 2.34[95% CI 1.05, 5.19]. There were no significant differences in the rate of increase of flu-like symptoms, rash, or liver enzymes., Conclusions: The evidence of DMARD efficacy in PsA is certainly limited, basically due to the small number of studies, dissimilar outcomes being evaluated, high withdrawal rates, and absence of new published studies. With regard to adverse effects, only GI events and headaches were significant compared to placebo.