A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis

Objective: Treatments for psoriatic arthritis (PsA) range from high-cost agents such as tumour necrosis factor (TNF) inhibitors evaluated in large randomised control trials (RCTs) and low-cost disease-modifying anti-rheumatic drugs (DMARDs) studied in less detail. We compared their efficacy and toxicity in a systematic review. Methods: We searched Medline, PubMed and EmBase (1966-2006) for RCTs in PsA. We included RCTs that were randomised, placebo-controlled, in English, involved current treatments and only enrolled PsA patients. Efficacy was assessed by the numbers of patients withdrawn for lack of effect; toxicity by withdrawals for adverse events. RCTs were compared using risk ratios (RR) with 95% confidence intervals (CI). Results: We identified 32 potentially relevant RCTs; 14 were excluded because they involved unused agents, were unblinded, were not placebo-controlled and enrolled patients with other diseases. 18 studies were included in the meta-analysis assessing DMARD monotherapy (11), DMARD combinations (one), TNF inhibitors (five) and alefacept (one). Treatment was more effective than placebo (RR=0.35; 95% CI 0.25, 0.49) but caused more toxicity (RR=2.33; 95% CI 1.61, 3.37). There was evidence that gold, sulfasalazine, leflunomide and TNF inhibitors were effective; gold and TNF inhibitors showed the largest effect sizes; TNF inhibitors had the best efficacy/toxicity ratio (number needed to harm/number needed to treat=0.25); tolerability was least with gold and leflunomide. Conclusions: Efficacy/toxicity ratios were highest with TNF inhibitors followed by leflunomide, gold and sulfasalazine. Gold, though effective, has excessive toxicity and sulfasalazine, though of low toxicity, was also relatively ineffective.