Ettore Silvagni et al. favoured the currently recommended use of disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), revealing a higher risk of drug withdrawal for TNFi monotherapy as compared to the combination. It suggested that, among bDMARDs, etanercept (ETA) should be preferred over INF and to a lesser extent Adalimumab (ADA) when a first-line monotherapy is a requisite. The positive impact of Leflunomide (LFN), Methotrexate (MTX), or combination of csDMARDs in improving the bDMARDs persistence has been confirmed in this study.

The present study was carried out to comparatively evaluate the persistence on the treatment of various bDMARDs when administered alone i.e. monotherapy compared with combination with csDMARDs in rheumatoid arthritis (RA) patients receiving first-line biologics.

This retrospective observational study comprised of data extracted from healthcare databases of Lombardy Region, Italy between 2004-2013, as a part of the RECord-linkage On Rheumatic Diseases study. RA patients administering first-line approved therapy of bDMARDs were considered for the analyses. Cox proportional hazard models were utilized to evaluate drug survival. The results are described as crude and adjusted for prespecified confounders (prior infections, age, disease duration, sex, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs) Charlson Comorbidity Index (CCI)) and HRs and 95% CI,

Four thousand four hundred seventy-eight patients with RA were considered for the analysis (17.84% monotherapy). The most prescribed first line biologics were infliximab, etanercept and adalimumab. Lower use of glucocorticoids and NSAIDs, higher CCI and longer duration of disease were noted with bDMARD monotherapy. The combination was linked to a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88) in comparison to monotherapy. Among monotherapies, infliximab (2.41, 95% CI 1.85 to 3.15) and adalimumab (1.28, 95% CI 1.03 to 1.59) were associated with greater risk of failure while keeping etanercept as a reference. The risk of bDMARD withdrawal was reduced with the concomitant administration of leflunomide (0.80, 95% CI 0.65 to 0.98), csDMARD combinations (0.77, 95% CI 0.68 to 0.87) or methotrexate (0.78, 95% CI 0.70 to 0.87).

Lower retention rate was observed with adalimumab and infliximab as compared to etanercept. It will be difficult to achieve productive outcomes with other biologics due to the presence of small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors. Longer survival on bDMARD was observed with concomitant leflunomide, methotrexate and csDMARDs combination. Finally, the study results confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and support the currently recommended use of bDMARDs in combination with csDMARDs.