OP0076 LONG-TERM OUTCOMES OF REPEAT CYCLES OF RITUXIMAB FOR SYSTEMIC MANIFESTATIONS OF SJOGREN’S DISEASE: MULTICENTRE UK COHORT STUDY
Authors: M. Y. MD Yusof, J. Berry, I. Turtsevich, S. Pepple, J. Arnold, E. M. Vital, M. Gupta, S. Bowman, C. Ciurtin, B. A. Fisher, W. F. Ng, M. Al-Obaidi, E. Price
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Randomised controlled trials of rituximab (RTX) in adults with Sjogren's disease (SjD) aimed to alleviate glandular symptoms and fatigue. A handful of real-world data have supported its effectiveness in systemic manifestations of SjD but data for childhood onset disease are limited. There is also a paucity of data on the outcome of repeat RTX cycles in both childhood and adult onset SjD. Therefore, the efficacy of repeat cycles in first cycle responders or non-responders (as previously demonstrated in rheumatoid arthritis, RA) is unclear. <h3>Objectives:</h3> To evaluate the long-term outcomes of repeat cycles of RTX in SjD responders and non-responders using whole life course approach. <h3>Methods:</h3> A retrospective observational study was conducted in RTX-treated SjD patients from 7 UK centres for over 15 years using a standardised proforma. Clinical response at 6 months was defined as ≥3 reduction of ESSDAI from baseline, as well as physicians' decision to continue RTX therapy. 5-year drug retention was analysed using Kaplan-Meir survival analysis. <h3>Results:</h3> Of 77 patients included in the study, 70 (91%) were females, 57 (74%) were of European ancestry, 9 (12%) were childhood onset, 73 (94%) were ANA-positive, 49 (64%) were on concomitant immunosuppressant and 43 (56%) were on oral prednisolone. Mean (SD) age was 49 (18) years, median (IQR) disease duration was 6 (2-10) years and 34 (44%) had severe SjD (i.e. ESSDAI&gt;13). Main domains for RTX were articular (64%), biological (53%), haematological (36%), skin (34%), and PNS (25%). In a total follow-up of 346PY, 284 RTX cycles were administered. In Cycle 1 (C1) RTX, of 73/77 patients with 6-month data, the proportion of patient achieving ESSDAI response from baseline was 58/73 (80%). There was no difference in response between childhood vs adult onset (88% vs 79%; p=1.0). There were significant reductions in daily prednisolone dose and IgG levels at 6 months (all p&lt;0.05). Of 54/77 patients with peripheral B-cell data, achieving complete depletion was associated with ESSDAI response (p=0.037). Of 33/58 C1 responders who received RTX re-treatment, 24/33 (74%) continued to respond in C2. Loss of response in C2 was due to secondary non-depletion non-response (2NDNR) associated with anti-RTX antibodies (n=6/33; 18%) as we previously observed in SLE[1] and inefficacy (n=3). Of C1 non-responders, 12/15 were retreated but only 4/12 (33%) responded in C2. At the date of last review (Jan 2024), 26/77 (34%) had discontinued RTX [primary inefficacy=6, secondary inefficacy=7, 2NDNR or other allergic reaction=7, death=6 (malignancy=2, frailty=1, cardiac arrest=1, intracerebral bleed=1, palliative following neck trauma=1)]. 5-year Kaplan-Meir drug retention curve is shown in Figure 1. <h3>Conclusion:</h3> Our long-term data showed a good RTX retention rate for the treatment of systemic manifestations of SjD. In first cycle non-responders, re-treatment did not appear to be effective in SjD, in contrast to RA. About 1 in 6 patients lost response with repeat cycles and this was associated with a 2NDNR phenomenon. The use of type 2 anti-CD20mAbs may increase and sustain clinical response rates to B-cell depleting agents. <h3>REFERENCES:</h3> [1] Md Yusof et al. ARD 2017. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Md Yuzaiful Md Yusof Alumis, Novartis and Roche, Aurinia Pharmaceuticals and UCB, Joe Berry: None declared, Inga Turtsevich: None declared, Sophie Pepple: None declared, Jack Arnold: None declared, Edward M. Vital Roche, GSK, AstraZeneca, Aurinia Pharmaceuticals, Lilly and Novartis, Roche, AstraZeneca and Sandoz, Monica Gupta: None declared, Simon Bowman: None declared, Coziana Ciurtin: None declared, Ben A Fisher: None declared, Wan-Fai Ng: None declared, Muthana Al-Obaidi: None declared, Elizabeth Price: None declared.