Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent?

Abstract

Background: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit.

Objective: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients.

Methods: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders.

Results: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug.

Conclusion: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

Figure 1

Effect modification by prior aTNF ineffectiveness. Change in rheumatoid arthritis (RA) disease activity after initiation of an alternative tumour necrosis factor antagonist (aTNF) or rituximab (RTX). The longitudinal improvement in RA disease activity (28-joint count Disease Activity Score (DAS28)) over the average treatment time is represented: (A) for patients switching because of ineffectiveness to the previous aTNF and (B) for patients switching because of adverse effects to the previous aTNF or other reasons. The improvement of DAS28 was more favourable with RTX only for patients with a history of prior aTNF ineffectiveness (effect modification  = 0.005). The progression trajectories depicted are adjusted for differences in baseline disease characteristics and treatment characteristics (supplementary appendix). Vertical lines represent the 95% confidence interval of the mean (only lower-bound interval for the RTX estimates).

Figure 2

Effect modification by the type of aTNF switch. Change in rheumatoid arthritis (RA) disease activity after initiation of an alternative tumour necrosis factor antagonist (aTNF) versus rituximab (RTX). The longitudinal improvement in RA disease activity (28-joint count Disease Activity Score (DAS28)) over the average time on treatment is represented: (A) for patients switching from one aTNF monoclonal antibody (aTNF-AB) to another aTNF-AB; (B) for patients switching from an aTNF soluble receptor (aTNF-SR) to an aTNF-AB. No significant effect modification existed by the type of aTNF switch (p = 0.27). The progression trajectories depicted are adjusted for differences in baseline disease characteristics and treatment characteristics (supplementary appendix). Vertical lines represent the 95% confidence interval of the mean (only lower-bound interval for the RTX estimates).

Figure 3

Effect modification by the number of prior aTNF failures. Change in rheumatoid arthritis (RA) disease activity after initiation of an alternative tumour necrosis factor antagonist (aTNF) versus rituximab (RTX). The longitudinal improvement in RA disease activity (28-joint count Disease Activity Score (DAS28) over the average time on treatment is represented: (A) for patients switching after a single prior aTNF failure and (B) for patients switching after multiple prior aTNF failures. No significant effect modification existed by the type of aTNF switch (p = 0.61). The progression trajectories depicted are adjusted for differences in baseline disease characteristics and treatment characteristics (supplementary appendix).