Comparative Efficacy of First-line Biological Monotherapy in RA: A Retrospective Analysis of the RECord-linkage On Rheumatic Diseases Study on Health Care Administrative Databases

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Comparative Efficacy of First-line Biological Monotherapy in RA: A Retrospective Analysis of the RECord-linkage On Rheumatic Diseases Study on Health Care Administrative Databases
Key Take-Away: 

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 study results strengthen the positive influence of Methotrexate (MTX), leflunomide (LFN) or combination of csDMARDs in ameliorating the bDMARDs persistence. 


These analyses focus to comparatively examine the persistence on the treatment of different bDMARDs when administered in 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. Analyses consist of patients with RA starting the first-line approved course of bDMARDs and examined drug survival via Cox proportional hazard models. The results are described as HRs and 95% CI, crude and adjusted for prespecified confounders (disease duration, sex, age, Charlson Comorbidity Index (CCI), prior infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).



Four thousand four hundred seventy-eight patients with RA were considered for the analysis (17.84% monotherapy). Adalimumab, etanercept, and infliximab were the most prescribed first-line biologics. bDMARD monotherapy had longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. As compared with monotherapy, the combination was associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Considering etanercept as a reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had a higher risk of failure among the monotherapies. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) decreased the risk of bDMARD withdrawal.



Adalimumab and infliximab monotherapies depicted lower retention rate as compared to etanercept. The relatively small number of therapeutic courses distinct from tumour necrosis factor (TNF) inhibitors makes it more challenging to achieve conclusive results with other biologics. The concomitant methotrexate, leflunomide and csDMARDs combination found to be associated with longer survival on bDMARD. The study data confirmed 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.


BMJ Open


Original title of article:

Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases


Ettore Silvagni et al.

Exploratory, Etanercept (ETA) , Adalimumab (ADA), Infliximab, Methotrexate (MTX), leflunomide (LFN) , Tumour necrosis factor (TNF) inhibitors, bDMARDs, csDMARDs, NSAIDs, Retrospective observational study, Cox proportional hazard models
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