Objective To investigate the association between baseline disease activity and the occurrence of flares after adalimumab tapering or withdrawal in patients with rheumatoid arthritis (RA) in sustained remission.
Methods The PREDICTRA phase IV, randomised, double-blind (DB) study (ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels, and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Patients) enrolled patients with RA receiving adalimumab 40 mg every other week who were in sustained remission ≥6 months. After a 4-week, open-label lead-in (OL-LI) period, patients were randomised 5:1 to DB adalimumab taper (every 3 weeks) or withdrawal (placebo) for 36 weeks. The primary endpoint was the association between DB baseline hand and wrist MRI-detected inflammation with flare occurrence.
Results Of 146 patients treated during the OL-LI period, 122 were randomised to taper (n=102) or withdrawal (n=20) arms. Patients had a mean 12.9 years of active disease and had received adalimumab for a mean of 5.4 years (mean 2.2 years in sustained remission). Overall, 37 (36%) and 9 (45%) patients experienced a flare in the taper and withdrawal arms, respectively (time to flare, 18.0 and 13.3 weeks). None of the DB baseline disease characteristics or adalimumab concentration was associated with flare occurrence after adalimumab tapering. Approximately half of the patients who flared regained clinical remission after 16 weeks of open-label rescue adalimumab. The safety profile was consistent with previous studies.
Conclusions Approximately one-third of patients who tapered adalimumab versus half who withdrew adalimumab experienced a flare within 36 weeks. Time to flare was numerically longer in the taper versus withdrawal arm. Baseline MRI inflammation was not associated with flare occurrence.
Trial registration number NCT02198651, EudraCT 2014-001114-26.
- rheumatoid arthritis
- DMARDs (biologic)
- disease activity
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Handling editor Josef S Smolen
Presented at Part of this work was previously presented at the European Congress of Rheumatology, 12–15 June 2019, Madrid, Spain (Emery et al, Annals of the Rheumatic Diseases 2019;78:1132–1133).
Contributors Study concept and design: PE, GRB, EN, LS, PGC. Acquisition of data: PE, GRB, EN, LS, PGC. Analysis and interpretation of data: all authors. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: FK. All authors had access to the data, commented on the report drafts and approved the final submitted version.
Funding This study was funded by AbbVie.
Competing interests PE has received research grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. GRB has received research grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz and UCB. EN has received speaker fees from AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen and Celgene GmbH, and consulting fees from AbbVie. LS has received speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly and Roche. IL and FK are full-time employees of AbbVie and may hold AbbVie stock or stock options. PGC has received speakers' bureau or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, Novartis, Pfizer and Roche.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The study was conducted in accordance with the International Conference on Harmonisation guidelines, the ethical principles of Good Clinical Practice, local laws and the ethical principles of the Declaration of Helsinki. The study protocol was approved by an institutional review board or independent ethics committee at each study site.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymised, individual and trial-level data (analysis data sets), as well as other information (eg, protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.
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