Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24 week results of a phase 3 double blind randomized placebo-controlled study (rapid-PSA)

Background Certolizumab pegol (CZP) is a PEGylated humanized Fc-free anti-TNF that is clinically effective in rheumatoid arthritis [1]; this is the first report of clinical efficacy and safety of CZP in psoriatic arthritis (PsA). Objectives To assess efficacy and safety of CZP in patients (pts) with active PsA. Methods Pts with active PsA who had failed ≥1 DMARD and could have failed ≤1 anti-TNF were randomised 1:1:1 to placebo (PBO), or 400mg CZP at week (Wk) 0, 2 and 4 (loading dose, LD) followed by either 200mg CZP Q2W or 400mg CZP Q4W. Pts receiving PBO who failed to achieve a ≥10% decrease in TJC and SJC at both Wks14 and 16 were rescued and randomized at Wk16 to receive CZP 200mg Q2W or CZP 400mg Q4W following LD. The clinical primary endpoint was ACR20 response at Wk12. Non-responder imputation (NRI) was used for ACR and PASI75 responses; last observation carried forward (LOCF) for HAQ. Results 409 pts were randomized. Baseline demographics were similar between the 3 groups; 20% of pts had failed an anti-TNF. ACR20 response at Wk12 was significantly higher in both CZP arms vs PBO (Figure); the majority of the overall response rate observed at Wk24 was achieved by Wk12. Response with CZP was rapid, with a greater ACR20 response as early as Wk1 (7.4% for PBO vs 21.0% for CZP 200mg [p=0.001] and vs 23.0% for CZP 400mg [p<0.001]). At Wks12 and 24, both CZP arms showed significantly greater improvements than PBO in ACR50 and 70 (Figure). Greater improvements were also observed for both CZP arms in PASI75 (Figure), as well as in HAQ-DI at Wk 24 (HAQ-DI change from baseline; -0.50 [CZP combined] vs. -0.19 [PBO], p<0.001). Adverse events (AEs) occurred at the rates of 68% vs. 62% and serious AEs at 4% vs. 7% in PBO vs.CZP (combined dose), respectively. Two deaths occurred, one sudden death of unknown cause (CZP 400mg Q4W) and one myocardial infarct (CZP 200mg Q2W). The safety profile was similar to that observed with CZP in RA. Conclusions CZP effectively improved the signs and symptoms of arthritis, physical function and skin manifestations of psoriasis in pts with PsA with a safety profile similar to what has been observed in RA. (Table Presented).