Predicting Sustained Clinical Response to Rituximab in Moderate to Severe Systemic Manifestations of Primary Sjögren Syndrome.

Objective: To assess outcomes of repeat rituximab cycles and identify predictors of sustained clinical response in systemic manifestations of primary Sjögren syndrome (pSS).

Methods: An observational study was conducted in 40 rituximab-treated patients with pSS. Clinical response was defined as a 3-point or more reduction in the European League Against Rheumatism (EULAR) Sjögren Disease Activity Index (ESSDAI) at 6 months from baseline. Peripheral blood B cells were measured using highly sensitive flow cytometry. Predictors of sustained response (within two rituximab cycles) were analyzed using penalized logistic regression.

Results: Thirty-eight out of 40 patients had moderate to severe systemic disease (ESSDAI >5). Main domains were articular (73%), mucocutaneous (23%), hematological (20%), and nervous system (18%). Twenty-eight out of 40 (70%) patients were on concomitant immunosuppressants. One hundred sixty-nine rituximab cycles were administered with a total follow-up of 165 patient-years. In cycle 1 (C1), 29/40 (73%) achieved ESSDAI response. Of C1 responders, 23/29 received retreatment on clinical relapse, and 15/23 (65%) responded. Of the 8/23 patients who lost response, these were due to secondary non-depletion and non-response (2NDNR; 4/23 [17%] as we previously observed in systemic lupus erythematosus with antirituximab antibodies, inefficacy = 2/23, and other side effects = 2/23). Within two cycles, 13/40 (33%) discontinued therapy. In multivariable analysis, concomitant immunosuppressant (odds ratio 7.16 [95% confidence interval: 1.37-37.35]) and achieving complete B-cell depletion (9.78 [1.32-72.25]) in C1 increased odds of response to rituximab. At 5 years, 57% of patients continued on rituximab.

Conclusion: Our data suggest that patients with pSS should be co-prescribed immunosuppressant with rituximab, and treatment should aim to achieve complete depletion. About one in six patients develop 2NDNR in repeat cycles. Humanized or type 2 anti-CD20 antibodies may improve clinical response in extra-glandular pSS.