AB0293 IDENTIFYING PREDICTORS OF SHORT-TERM RESPONSE TO RITUXIMAB IN PRIMARY SJOGREN’S SYNDROME
Authors: S. Pepple, J. Arnold, E. Vital, A. Rawstron, C. Pease, S. Dass, P. Emery, M. Y. MD Yusof
Journal: Annals of the Rheumatic Diseases (2021)

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&lt;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. References: [1]Md Yusof et al. ARD 2017 (2520 characters – allowed around 2600 as Table 1 is included too) Table 1. MVA logistic regression of risk factors for RTX non-response Predictors Continued Response (N=27) Non-response within 2 RTX Cycles (N=13) Univariable OR (95% CI); p-value Multivariable OR (95% CI); p-value Age, mean (SD) per 10 years 55 (14) 52 (12) 0.87 (0.53-1.41); 0.572 Excluded from final model Disease duration, median (IQR) 5 (2-9) 6 (3-9) 0.97 (0.87-1.08); 0.565 Excluded from final model Concomitant IS, % 81.5% 30.8% 0.10 (0.02-0.46); 0.003 0.07 (0.01-0.52); 0.010 IgG, mean (SD), g/L 15.5 (6.3) 18.4 (5.8) 1.08 (0.97-1.20); 0.175 1.13 (0.97-1.32); 0.116 Clinical ESSDAI, median (IQR) 10 (6-16) 8 (6-10) 0.96 (0.85-1.08); 0.487 0.91 (0.79-1.05); 0.185 Baseline Plasmablast (x1000), 10 9 cells/L, median (IQR) 2.6 (1 -5.2) 2.3 (1.6-9.5) 1.00 (0.94-1.07); 0.885 Excluded from final model Complete B-cell depletion post-RTX, % 55.6% 8.5% 0.07 (0.01-0.64); 0.018 0.04 (0.02-0.82); 0.036 Disclosure of Interests: Sophanit Pepple: None declared, Jack Arnold: None declared, Edward Vital Grant/research support from: Dr Vital has received honoraria and research grant support from Roche, Andrew Rawstron: None declared, Colin Pease: None declared, Shouvik Dass Grant/research support from: Dr Dass has received honoraria from Roche, Paul Emery Consultant of: Professor Emery has received consultant fees from Roche., Grant/research support from: Professor Emery has received research grants paid to his employer from Roche., Md Yuzaiful Md Yusof: None declared