Complement system in psoriatic arthritis: A useful marker in response prediction and monitoring of anti-TNF treatment

Objective: Treatment with anti-TNF agents is well established in psoriatic arthritis (PsA). Anti-TNF agents are capable of modulating complement activity in vitro but there are no data on the in vivo effect. Anti-TNF have high costs and potential risks, thus, there is an urgent need for accurate predictors of response. We aimed at studying the usefulness of erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), and complement for response prediction and monitoring of anti-TNF treatment in PsA patients. Methods: Fifty-five patients were included consecutively before starting etanercept or adalimumab. ESR, CRP, plasma complement C3, C4, and C3 and B cleavage fragments were evaluated at baseline and after 22 weeks of anti-TNF treatment. Disease activity was measured with DAS28 and response to therapy with EULAR criteria. Complement was evaluated at baseline in 30 healthy subjects as well. Results: At baseline, C3 and C4 levels were significantly higher than in controls (C3 126.9±22 vs. 110±25 mg/dl, p=0.000002; C4 31.2±9.2 vs. 22.7±8.3 mg/dl, p=0.0003). After anti-TNF therapy, C3 and C4 levels were significantly reduced to normalization (p=0.0009 and 0.0005, respectively) and ESR, CRP and DAS28 showed a significant reduction (p=0.002, 0.004 and 0.0001, respectively). Split products of C3 and B were not observed at baseline and after 22 weeks. Higher baseline C3 levels were associated with EULAR non-response (p=0.011). Conclusion: PsA patients with moderate to severe disease show elevated C3 and C4 levels, reverted by anti-TNF treatment. High C3 may be considered a hallmark of inflammation and C3 revealed the highest predictive value for response to anti-TNF.