Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA)

Abstract

Objectives: To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA).

Methods: Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index.

Results: Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (-0.50 vs -0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed.

Conclusions: Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.

Keywords: Anti-TNF; Psoriatic Arthritis; Treatment.

Figures

Figure 1

Study design and patient disposition. *All patients received trial medication; CZP: certolizumab pegol; Q2W: every 2 weeks; Q4W: every 4 weeks; LD: loading dose; PsA: psoriatic arthritis; sc: subcutaneous; Wk: week. (A) Study design of RAPID-PsA. (B) Patient disposition to week 24.

Figure 2

Effects of certolizumab pegol treatment on PsA disease activity and psoriasis. CZP: certolizumab pegol; Q2W: every 2 weeks; Q4W: every 4 weeks; PBO: placebo; PsA: psoriatic arthritis. (A) Percentages of patients achieving a response according to the American College of Rheumatology Criteria for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement (ACR70) at week 12 and week 24, by treatment group. *p†p=0.003 versus placebo. (B) Percentages of patients achieving an ACR20, ACR50 and ACR70 response over time, by treatment group. *p<0.001; †p=0.005 versus placebo. (C) Percentages of patients with 3% body surface area (BSA) psoriasis at baseline achieving a Psoriasis Area and Severity Index 50% improvement (PASI50), 75% improvement (PASI75) and 90% improvement (PASI90) at week 12 and week 24. No statistical testing was conducted on PASI50 response. *Nominal p value <0.005 versus placebo. (D) Percentages of patients with 3% BSA psoriasis at baseline achieving a PASI50, PASI75 and PASI90 response over time, by treatment group. No statistical analysis was conducted on PASI50 response. *Nominal p value <0.001; †p value=0.016 versus placebo.

Figure 3

Effect of CZP in patients with and without prior TNF inhibitor exposure at week 24 in terms of ACR response and the kinetics of ACR response. CZP, Certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks; PBO, placebo; TNF, tumour necrosis factor. (A) Percentages of patients with and without prior TNF inhibitor exposure achieving a response according to the American College of Rheumatology Criteria for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement (ACR70) at week 24, by treatment group. (B) Percentages of patients with prior TNF inhibitor exposure achieving an ACR20, ACR50, and ACR70 response over time, by treatment group. (C) Percentages of patients without prior TNF inhibitor exposure achieving an ACR20, ACR50 and ACR70 response over time, by treatment group; *p†p<0.05 versus placebo.