AB0293 IDENTIFYING PREDICTORS OF SHORT-TERM RESPONSE TO RITUXIMAB IN PRIMARY SJOGREN’S SYNDROME

Abstract

Background:Randomised controlled trials of rituximab (RTX) in primary Sjogren’s syndrome (pSS) have aimed to alleviate glandular symptoms and fatigue with only limited data on efficacy/effectiveness of the initial and repeat cycles of RTX on extra-glandular pSS.Objectives:To assess the effectiveness of RTX on extra-glandular symptoms and identify predictors of short-term response with a view to personalised B-cell depleting therapy in patients with pSS.Methods:An observational study was conducted in 40 consecutive RTX-treated pSS patients in a single centre for over 15 years. All patients fulfilled the 2002 AEG criteria and were CCP negative. Clinical response at 6 months was defined as ≥3 reduction of ESSDAI from baseline. B-cell subsets were measured using highly sensitive flow cytometry. Predictors of short-term response were analysed using penalised logistic regression.Results:38/40 (95%) patients were female, mean (SD) Age 54 (13.7) years, median (IQR) disease duration 5 (2-9) years, 39/40 (98%) had positive ANA, 26/40 (65%) were on concomitant immunosuppressant (IS). Mean (SD) ESSDAI at RTX initiation was 11.5 (6.7); main domains for RTX were articular (73%), skin (23%), PNS (15%) and muscular (15%). 169 RTX cycles were administered with a total follow-up of 165PY. In Cycle 1 (C1) RTX, the proportion of patient achieving ESSDAI response from baseline was 29/40 (73%; 95% CI 58-87). There were significant reductions in ESSDAI, daily prednisolone dose and IgG levels at 6 months (all p<0.05). Of C1 responders, 23/29 received retreatment on clinical relapse; of which 8/23 (35%) lost response [secondary non-depletion non response (2NDNR) associated with anti-RTX antibodies=4 (17%) as we previously observed in SLE[1], side effects=2, ineffective=2]. Of C1 non-responders, 9/11 were retreated but only 2/9 responded in C2. Overall, 13/40 (33%) discontinued RTX within two cycles. In multivariable analysis, concomitant IS and achieving compete B-cell depletion in C1 reduced non-response to RTX (Table 1).Conclusion:All pSS patients should be prescribed concomitant immunosuppressant with RTX and therapy should aim to achieve complete depletion. About 1 in 6 pSS patients lose response in repeat cycles which is associated with 2NDNR phenomenon. The use of humanised or type 2 anti-CD20mAbs should overcome these issues and improve the clinical response of extra-glandular pSS.