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.
- ankylosing spondylitis
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Handling editor Josef S Smolen
Contributors Substantial contributions to study conception and design: RL, DvdH, MD, XB, FVdB, KG, OD, LB, BH and LSG; contributions to analysis and interpretation of the data: RL, DvdH, MD, XB, FVdB, KG, OD, NdP, LB, BH, KT and LSG; drafting the article or revising it critically for important intellectual content: RL, DvdH, MD, XB, FVdB, KG, OD, NdP, LB, BH, KT and LSG; final approval of the version of the article to be published: RL, DvdH, MD, XB, FVdB, KG, OD, NdP, LB, BH, KT and LSG.
Funding This article was based on the original study AS0005/C-OPTIMISE (NCT02505542) sponsored by UCB Pharma. Support for third-party writing assistance for this article, provided by Jessica Patel, PhD, Costello Medical, UK, was funded by UCB Pharma in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3).
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.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting or dissemination plans of this research. Refer to the Methods section for further details.
Patient consent for publication Not required.
Ethics approval The study was approved by institutional review boards and independent ethics committees at participating sites and was conducted in accordance with local regulations and the International Conference on Harmonisation Good Clinical Practice requirements, based on the Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Underlying data from this manuscript may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.organd a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
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