Which advanced treatment should be used following the failure of a first-line anti-TNF in patients with rheumatoid arthritis? 15 years of evidence from the Quebec registry RHUMADATA.

Background: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe RA. Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first TNF inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA.

Methods: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up or 25 November 2022. Kaplan-Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted and propensity score-adjusted imputed data analyses were produced.

Results: Six hundred eleven patients [320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)] were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44-0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18-0.84) had better retention than TNFi after adjusting for patient characteristics.

Conclusion: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.