Abstract
Objective
The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi.
Method
A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs.
Results
The cohort comprised 1434 patients. The mean age was 53.8 years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate.
Conclusions
Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.
Funding
The study was supported by the Italian Society for Rheumatology.
Disclosure statement
Carlo Alberto Scirè received consultancy fees from AbbVie and Bristol-Meyers Squibb. All the other authors declare that they have no conflict of interest.
Author contributions
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors contributed to the study conception and design. Material preparation and data collection were performed by Greta Carrara, Anna Zanetti, Alen Zabotti, Ettore Silvagni, Gian Domenico Sebastiani, Marco Sebastiani, and Carlo Alberto Scirè. Analysis was performed by Greta Carrara, Lisa Argnani, and Anna Zanetti. The first draft of the manuscript was written by Greta Carrara, Lisa Argnani, Anna Zanetti, and Carlo Alberto Scirè, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Data availability
Permission for use of data was granted by the General Directorate of Health of the Lombardy Region for the objectives of this project, and data are not usable for other purposes. R codes of the analyses are available upon request.