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Baseline methotrexate use has been found to be able to predict remission flare ups in patients with rheumatoid arthritis.

Half of patients with rheumatoid arthritis (RA) in remission experience flares within 6 months after stopping disease-modifying antirheumatic drugs (DMARDs). The strongest predictor of these flares in the BIO-FLARE study was baseline methotrexate use.

RA flares remain poorly understood and the unpredictable flare-ups can significantly impact the quality of life of patients. Dr Fiona Rayner (Newcastle University, UK) and her team aimed to identify clinical predictors of flares in the BIO-FLARE study (ISRCTN16371380) and to develop a predictive model for patients with RA in remission who have stopped conventional synthetic DMARDs.

This multicenter, prospective, experimental medicine program recruited 121 participants with RA in remission (DAS28-CRP <2.4) from September 2018 to December 2020. Eligible patients were on methotrexate, sulfasalazine, or hydroxychloroquine, and all treatments were stopped without tapering. Participants were followed up at multiple intervals (weeks 2, 5, 8, 12, and 24) or until a flare occurred. The primary outcome was the time to flare, (defined as DAS28-CRP ≥3.2 at any visit or DAS28-CRP ≥2.4 reconfirmed within 14 days).

Over the 24-week study period, 52.3% of the participants experienced a confirmed flare with a median time-to-flare of 63 days. The following baseline variables were significantly associated with time-to-flare:

• baseline methotrexate use (HR 2.92; P=0.02);
• female sex (HR 1.89; P=0.03);
• rheumatoid factor (RF) levels, per 10 IU/ml (HR 1.03; P=0.001); and
• anti-citrullinated protein antibody (ACPA) levels (HR 1.03; P=0.01).

The BIO-FLARE study showed that approximately half of patients with RA in remission experience a flare within 6 months after conventional synthetic DMARD treatment is stopped. The authors used these variables to build a predictive model for estimating the risk for flare over time. This model can be a valuable tool for clinicians to estimate the risk for flare in individual patients. Ongoing studies aim to identify immune biomarkers to strengthen this model and provide insights into the biology of flares and remission in RA.