Rituximab Done: What's Next in Rheumatoid Arthritis?

A European Observational Longitudinal Study Assessing the Effectiveness of Biologics After Rituximab Treatment in Rheumatoid Arthritis

Ulrich A. Walker; Veronika K. Jaeger; Katerina Chatzidionysiou; Merete L. Hetland; Ellen-Margrethe Hauge; Karel Pavelka; Dan C. Nordström; Helena Canhão; Matija Tomšič; Ronald van Vollenhoven; Cem Gabay


Rheumatology. 2016;55(2):230-236. 

In This Article

Abstract and Introduction


Objective. To compare the effectiveness of biologics after rituximab (RTX) treatment in RA.

Methods. The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries for the Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6 months or less prior to the new biologic and had a baseline visit within 21 days of starting the new biologic.

Results. Two hundred and sixty-five patients were analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs 14%, P < 0.001). The HAQ disability index improved in all treatment groups (P < 0.001), but did not differ between biologics, as did drug retention rates. The reasons for discontinuation of RTX and the number of previous biologics had no influence on outcomes.

Conclusion. In this observational cohort of patients who discontinued RTX, TCZ provided a better control of RA than ABA or TNFi.


The development of biologic DMARDs (bDMARDs) has represented a major therapeutic advance in the management of RA, because bDMARDs are effective in improving the symptoms and signs of RA and in preventing structural joint damage. bDMARDs with different modes of action have become available; for example, TNF-α inhibitors (TNFi), a B-cell depleting antibody [rituximab (RTX)], an inhibitor of co-stimulatory mechanisms [abatacept (ABA)] and an IL-6 antagonist [tocilizumab (TCZ)]. One bDMARD may be switched to another with a different mode of action, particularly in cases of failure or recurrence of class-associated side effects. With the growing availability of expensive therapeutic agents in RA, it becomes increasingly important to tailor the treatment to the individual patient in order to maximize the cost–benefit and minimize time on suboptimal therapies.

Observational studies suggest that in the case of active RA despite biologic treatment, switching to a new drug class may be more effective than switching to a bDMARD with the same mode of action.[1–3] In RA patients with inadequate response to TNFi, the efficacy of other bDMARD classes, such as ABA, RTX or TCZ, has been examined in large randomized controlled trials,[4–6] but data from randomized studies are not available for patients failing RTX. Furthermore, there is a lack of information about the effectiveness and safety of cycling strategies in patients who have failed second- or third-line bDMARDs. This makes it difficult for physicians to choose the most effective therapeutic strategy for patients who have been exposed to several bDMARDs. Given that most studies with regard to bDMARDs after B-cell depletion have focused on drug safety[7,8] and there is a paucity of information on effectiveness, we aimed to analyse the effectiveness of switching to alternative modes of action after RTX discontinuation.