Failure and multiple failure for disease modifying antirheumatic drugs in rheumatoid arthritis: Real-life evidence from a tertiary referral center in Italy

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments’ clinical response. Goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. OBJECTIVE: To investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors’ according to RA patient characteristics in a real-world setting. METHODS: 718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. Patients failing to at least two csDMARDs or bDMARDs’ drug for inefficacy were defined “csDMARDs multifailure” and “bDMARDs multifailure”, respectively. Discontinuation of at least two cs- and bDMARDs was termed “global multifailure”. RESULTS: In total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. Reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. Longstanding disease (≥ 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). Thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). CONCLUSIONS: Different causes of drug discontinuation were observed on DMARDs treatments. Demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets.