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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 (Im P act of R esidual Inflammation Detected via Imaging T E chniques, D rug Levels, and Patient Characteristics on the Outcome of Dose Taper I ng of Adalimumab in C linical Remission Rheumatoid Ar T hritis ( 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., Competing Interests: 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., (© 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.)

Objectives: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target., Methods: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models., Results: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52)., Conclusion: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission., Competing Interests: Competing interests: SR: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, MSD, Novartis and Sanofi. RL: Received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy BV. DvdH: Received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology BV. AS: Received speaking fees from Novartis. OFG: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, Celgene, Novartis, UCB, Pfizer, Amgen and Janssen. MØ: Received research support, consultancy fees and/or speaker fees form Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. OE: Received grants and personal fees from Pfizer, Abbvie, Roche, Janssen, Novartis and Lilly. JCT: Received research grants and/or consulting fees from AbbVie, Amgen, Celgene, Centocor, Lilly, Medexux/Medac, Merck, Novartis, Pfizer, Sandoz and Sanofi. ML: Received advisory board honoraria from AbbVie, Actelion, Boehringer Ingelheim, BMS, Janssen, Novartis, Pfizer, Sanofi, Roche and an unrestricted educational grant from AbbVie. GF: Received research grants and/or consultancy fees from Novartis, Roche, BMS, Pfizer, AbbVie, Lilly, Janssen, MSD, Boehringer-Ingelheim and UCB. MB: Received research grants from AbbVie Co.KG, Roche, Novartis and Pfizer; received speaking fees from Actelion, AbbVie Co.KG, BMS, Celgene, Gilead, Janssen, Lilly, MSD, Novartis, Sanofi Genzyme, Roche, Pfizer and UCB. GB: Received consulting fees from Eli Lilly, Janssen, Novartis and Pfizer; received speaker fees from BMS, Merck and Pfizer. Industry support for investigator-initiated research initiatives from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Jannsen, Merck, Pfizer, Roche and UCB. BC: Received consulting fees from AbbVie, BMS, Eli-Lilly, Gilead, Janssen, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. TS: Received consulting fees from Lilly, Novartis, Pfizer and Sanofi; received research financial support from Pfizer and Lilly. AS: Received research grants and/or consultancy fees from AbbVie, BMS, Chugai, Eli Lilly, MSD, Nordic pharma, Novartis, Pfizer, Sanofi and UCB. MD: Received research grants and/or honorarium fees for his participation at advisory boards and/or symposium organised by Pfizer, AbbVie, Lilly, Novartis, BMS, Roche, UCB and Merck. MR: Received advisory board honoraria, consultancy fees and/or speaker fees from Abiogen, Amgen, Abbvie, BMS, Celgene, Eli-Lilly, MSD, Novartis, Pfizer, Sanofi, Sandoz and UCB. MG: Received advisory board honoraria, consultancy fees and/or speaker fees from Abbvie, Alfa-Sigma, BMS, Celgene, MSD, Novartis, Pfizer, Roche and Sanofi. LS: Received speaker fees from Amgen,Eli Lilly, Abbvie, Roche and BMS. AGC: Received consultancy fees from BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, AbbVie, Celgene and Nordic Pharma; received research grants from Pfizer, UCB, AbbVie and Celgene. CB: Received advisory board honoraria from Gilead, Pfizer, Novartis, Eli Lily, Roche and Amgen; speaking fees from UCB, BMS and Abbvie. COB III: Consultant to Abbvie, BMS, Gilead, Lilly, Pfizer, Genentech/Roche and Sanofi/Regeneron. Grant support from BMS and Janssen. PPT: Currently an employee of Kintai Therapeutics, Cambridge MA. Kintai Therapeutics has not been involved in this work. HBH: Received fees for speaking and/or consulting from AbbVie, BMS, Pfizer, UCB, Roche, MSD and Novartis. WPM: Received consulting fees from AbbVie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma and is Chief Medical Officer of CARE Arthritis Limited., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)