4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis

Abstract

Objective: To report the efficacy, patient-reported, radiographic and safety outcomes of 4 years' certolizumab pegol (CZP) treatment in patients with psoriatic arthritis (PsA).

Methods: RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Week 24, dose-blind to Week 48 and open-label (OL) to Week 216. Patients were randomised 1:1:1 to either placebo or CZP 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W) (following 400 mg at Weeks 0/2/4). Patients randomised to CZP continued their assigned dose in the OL period. Patients randomised to placebo were re-randomised to CZP 200 mg Q2W or 400 mg Q4W (post-loading dose) at Week 16 (early escape) or after the double-blind phase. We present observed and imputed data; missing values were imputed using non-responder imputation (NRI) for categorical and last observation carried forward (LOCF) for continuous measures.

Results: 409 patients were randomised; 20% (54/273) of Week 0 patients randomised to CZP had prior anti-tumour necrosis factor (TNF) exposure; 67% (183/273) completed 216 weeks. By Week 48, 60.4% of patients achieved Disease Activity Index for Psoriatic Arthritis low disease activity or remission, which was maintained; 66.3% achieved these outcomes at Week 216 (NRI). At Weeks 48 and 216, 39.2% of patients achieved minimal disease activity (NRI). 75% reduction in Psoriasis Area and Severity Index responses were 65% and 52% at Weeks 48 and 216 (NRI). Total resolution rates for enthesitis, dactylitis and nail psoriasis, at 4 years, were 71%, 81% and 65%, respectively (LOCF). Structural damage progression was low over 4 years' treatment. No new safety signals were identified after Week 96.

Conclusions: CZP efficacy in treating PsA was maintained over 4 years, in patients both with and without prior anti-TNF exposure, with no new safety signals identified.

Keywords: anti-tnf; dmards (biologic); psoriatic arthritis; tnf-alpha.

Conflict of interest statement

Competing interests: DvdH has received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma and is the director of Imaging Rheumatology bv. AD has received grants or research support from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma and consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. OFG has received grants or research support from AbbVie, Bristol-Myers Squibb, Janssen and Pfizer and consulting fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Pfizer and UCB Pharma and speaker fees from AbbVie, Celgene Janssen, Novartis, Pfizer and UCB Pharma. RF has received grants or research support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, MSD Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB Pharma and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and Sanofi-Aventis. DG has received grants or research support and consulting fees from Abbott, Amgen, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer and UCB Pharma. ABG has received consulting fees from Abbott (AbbVie), Aclaris, Actelion, Akros, Allergan, Amgen, Amicus, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Centocor (Janssen), Coronado, Crescendo Bioscience, CSL Behring Biotherapies for Life, Dermipsor, Dermira, Eli Lilly, Genentech, GlaxoSmithKline, Incyte, Karyopharm, Kineta One, KPI Therapeutics, Meiji Seika Pharma, Mitsubishi, Novartis, Novo Nordisk, Pfizer, Reddy Labs, Takeda, Tanabe Pharma Development America, TEVA, UCB Pharma, Valeant, Vertex and Xenoport and received grants or research support from Incyte and Janssen. BH, LB, OI-S and LP are employees of UCB Pharma. AT has received grants or research support, consulting fees and speaker fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. JW has received grants or research support and consulting fees from UCB Pharma. PJM has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sun and UCB Pharma; grants or research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun, UCB Pharma and Zynerba and speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer and UCB Pharma.

Figures

Figure 1

(A) RAPID-PsA trial design, (B) patient disposition to Week 216 and (C) Kaplan-Meier plot to time of withdrawal for any reason, or due to lack of efficacy or adverse events, for patients randomised to CZP at Week 0. †Only 121 of the 123 Week 0 CZP 200 mg Q2W patients who completed the dose-blind period of treatment went on to start the open-label period of treatment. ‡One fewer patient went on to start the open-label period of treatment. *Censored patients are those that withdrew due to reasons other than lack of efficacy or adverse event and those lost to follow-up. CZP, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks; TJC, tender joint count; SJC, swollen joint count.

Figure 2

ACR responder rates in patients receiving CZP from Week 0, stratified by prior anti-TNF exposure (A−C) and the proportion of patients receiving CZP from Week 0 achieving MDA (fulfilling ≥5/7 MDA criteria) (D), VLDA (fulfilling 7/7 MDA criteria) (E) and DAPSA LDA (>4 and ≤14) or remission (≤4) (F) over 4 years’ CZP treatment. Data are shown for the Randomised Set. ACR20/50/70: 20%, 50% and 70% or greater improvement in ACR score. ACR, American College of Rheumatology; CZP, certolizumab pegol; DAPSA, Disease Activity Index for Psoriatic Arthritis; LDA, low disease activity; LOCF, last observation carried forward; MDA, minimal disease activity; NRI, non-responder imputation; OC, observed case; REM, remission; TNF, tumour necrosis factor; VLDA, very low disease activity.

Figure 3

PASI responder rates (A, B) and total resolution in (C) nail psoriasis, (D) enthesitis and (E) dactylitis in affected patients receiving CZP from Week 0, over 4 years’ treatment. Data are shown for the Randomised Set. PASI responder rates are given for patients with baseline skin involvement (≥3% body surface area affected by psoriasis). Total resolution rates for nail psoriasis, enthesitis and dactylitis are presented for patients affected by the respective conditions at baseline, respectively defined as modified Nail Psoriasis Severity Index >0 for nail psoriasis; Leeds Enthesitis Index >0 for enthesitis and Leeds Dactylitis Index >0, defined as having at least 1 digit affected and with a difference in circumference ≥10% compared with the opposite digit, for dactylitis. CZP, certolizumab pegol; LOCF, last observation carried forward; NRI, non-responder imputation; OC, observed case; PASI, Psoriasis Area and Severity Index.