Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction

Abstract

Background: The best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor certolizumab pegol (CZP) following achievement of sustained remission in patients with early axSpA.

Methods: C-OPTIMISE was a two-part, multicentre phase 3b study in adults with early active axSpA (radiographic or non-radiographic). During the 48-week open-label induction period, patients received CZP 200 mg every 2 weeks (Q2W). At Week 48, patients in sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 at Weeks 32/36 and 48) were randomised to double-blind CZP 200 mg Q2W (full maintenance dose), CZP 200 mg every 4 weeks (Q4W; reduced maintenance dose) or placebo (withdrawal) for a further 48 weeks. The primary endpoint was remaining flare-free (flare: ASDAS ≥2.1 at two consecutive visits or ASDAS >3.5 at any time point) during the double-blind period.

Results: At Week 48, 43.9% (323/736) patients achieved sustained remission, of whom 313 were randomised to CZP full maintenance dose, CZP reduced maintenance dose or placebo. During Weeks 48 to 96, 83.7% (87/104), 79.0% (83/105) and 20.2% (21/104) of patients receiving the full maintenance dose, reduced maintenance dose or placebo, respectively, were flare-free (p<0.001 vs placebo in both CZP groups). Responses in radiographic and non-radiographic axSpA patients were comparable.

Conclusions: Patients with early axSpA who achieve sustained remission at 48 weeks can reduce their CZP maintenance dose; however, treatment should not be completely discontinued due to the high risk of flare following CZP withdrawal.

Trial registration number: NCT02505542, ClinicalTrials.gov.

Keywords: ankylosing spondylitis; anti-TNF; spondyloarthritis.

Conflict of interest statement

Competing interests: RL: Consulting fees and/or research grants from AbbVie, Ablynx, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Galapagos, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Roche, Schering and UCB Pharma. DvDH: Consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma; director of Imaging Rheumatology BV. MD: Consultancy/speaker fees/research grants from AbbVie, Eli Lilly, Novartis, Merck, Pfizer and UCB Pharma. XB: Consultancy/speaker fees/research grants from AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer and UCB Pharma and grant/research support from AbbVie, Bristol-Myers Squibb and Celgene. FVdB: Consultancy fees from AbbVie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma; speakers bureau fees from AbbVie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. KG: Consulting fees, research grants and speaker fees from AbbVie, Celgene, MSD, Novartis, Pfizer and UCB Pharma. OD, NdP, LB, BH: Employees of UCB Pharma. KT: Independent statistician contracted to UCB Pharma. LSG: Grant/research support from AbbVie, Amgen, Novartis and UCB Pharma; consulting fees from Galapagos, Eli Lilly and Janssen.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

C-OPTIMISE study design (panel A) and patient disposition (panel B). AE, adverse event; axSpA, axial spondyloarthritis; CZP, certolizumab pegol; LD, loading dose; Q2W, every 2 weeks; Q4W, every 4 weeks. *Includes patients in the escape arm who completed week 96.

Figure 2

Patients free of flares during the maintenance period of C-OPTIMISE. Panel A shows the proportions of patients who did not experience flares following randomisation to CZP full maintenance dose (200 mg Q2W), CZP reduced maintenance dose (200 mg Q4W) or placebo. Panel B shows a Kaplan-Meier plot of time to flare. Missing values were imputed using non-responder imputation. Flare was defined as ASDAS ≥2.1 at two consecutive visits, or ASDAS >3.5 at any visit. CZP, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks.

Figure 3

Patients with radiographic and non-radiographic axial spondyloarthritis not experiencing flares during the maintenance period of C-OPTIMISE. axSpA, axial spondyloarthritis; CZP, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks.