Sat0144 understanding the Long-Term Outcome of Rituximab – Implications for Management

Abstract

Background:In patients with rheumatoid arthritis (RA), rituximab (RTX) is often prescribed after loss of response to TNF inhibitors; however, little is known about the long-term outcome of patients receiving treatment with RTX. Previous work [1,2] has shown that aiming for “complete B-cell depletion with clinical response” (CD-R) leads to an optimal management of the disease but unfortunately not all patients maintain this status. Whether CD-R can be regained with RTX retreatment remains unclear.Objectives:To assess the outcome of RA patients treated with consecutive cycles of RTX, focusing on those who achieved complete B-cell depletion with clinical response.Methods:A prospective 12 year observational study was conducted in RA patients who were treated with RTX in Leeds. Consecutive cycles of RTX consisting of 2 infusions of 1000mg were administered either on clinical relapse or a 6-monthly basis. B-cells were measured using highly sensitivity flow cytometry at 0 and 2 weeks post-RTX. Complete depletion (CD) was defined by total B-cell count <0.0001x109/L at week 2. Clinical response was defined by EULAR response criteria and CD-R was seen as the optimal outcome.Results:755 patients participated in the study of which 723 had complete data (see fig.1). The mean (range) number of RTX cycles administered was 3.8 (1-14). 76% (549/723) of patients reached CD-R at some stage during therapy while 24% (174/723) never did. The latter patients had a shorter period of RTX treatment vs CD-R with an OR of 7.98 after adjusting for age, gender, prior therapy with TNF-I and concomitant DMARDs (95% CI 5.86-10.86); p<0.001 (see fig.2). 84% of those who were retreated with RTX recovered CD-R (77% of them did it in the following cycle). Half of the patients that reached CD-R maintained it in prospective cycles but 47% lost it subsequently. A third of the patients that lost either clinical response or B-cell depletion were switched to other medication without receiving further cycles. Overall, at the end of the study, 55% of all patients treated with RTX (400/723) remained in CD-R.Conclusion:Most patients treated with RTX will achieve CD-R, but approximately half of them will lose this optimal status at some point. In patients who achieve CD-R but subsequently lose it, retreatment with RTX appears to be an effective strategy since 80% of them will regain it and will maintain long-term treatment with therapyReferences[1] Md Yusof, et al. EULAR2016[2] Garcia-Montoya, et al. EULAR2018Figure 1Figure 2Acknowledgement:Shouvik Dass Maya Buch Sarah BinghamDisclosure of Interests:Leticia Garcia-Montoya: None declared, Md Yuzaiful Md Yusof: None declared, Jean Baptiste Candelier: None declared, Andrew Rawstron: None declared, Edward Vital Grant/research support from: He has received honoraria and research grant support from Roche, GSK and AstraZeneca., Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz...

Lessons for rituximab therapy in patients with rheumatoid arthritis

“…Early depth of B-cell depletion with clinical response leads to a better long-term outcome (27) but unfortunately, at some point almost half of the patients lose CD-R with subsequent cycles (53). An observational study (53) with over 700 patients treated with rituximab showed that 84% of those who lost CD-R can regained it with further treatment, with 77% of them doing so in the following cycle. Interestingly, 33% of patients that either lost clinical response or did not achieve complete B-cell depletion, never received further treatment with the drug and were switched to other therapies.…”