Stopping DMARDs? These key factors predict RA flares

The BIO-FLARE study has shed light on predictors of rheumatoid arthritis (RA) flares, revealing that half of the patients in remission experience flares within 6 months of stopping DMARDs. Baseline use of methotrexate emerged as the strongest predictor, followed by female sex, rheumatoid factor levels, and anti-citrullinated protein antibody (ACPA) levels.

An incomplete understanding of the pathophysiological mechanisms underlying RA flares is an important obstacle to delivering effective treatment strategies [1]. Dr Fiona Rayner (Newcastle University, UK) and colleagues 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 [2].

This multicentre, prospective, experimental medicine programme 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. The 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 flares:

• baseline methotrexate use (HR 2.92; P=0.02);
• female sex (HR 1.89; P=0.03);
• rheumatoid factor levels per 10 IU/mL (HR 1.03; P=0.001); and
• ACPA levels (HR 1.03; P=0.01).

The BIO-FLARE study showed that approximately half of the patients with RA in remission experienced a flare within 6 months after conventional synthetic DMARD treatment was stopped. The authors used these variables to build a predictive model for estimating the risk of flare over time. This model can be a valuable tool for clinicians to estimate the risk of 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.

1. Bozzalla-Cassione E, et al. Front Med (Lausanne) 2022:9:852220.
2. Rayner F, et al. Flare and drug-free remission in rheumatoid arthritis: clinical predictors from the BIO-FLARE study. POS0068. EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 2024