Background/Purpose: Recent insights from open studies and randomized clinical trials have shown the effectiveness of  Rituximab (RTX) in controlling disease activity, patients’ subjective symptoms and patient-reported outcomes  in  primary Sjögren’s syndrome (SS). To date, only few cases of patients with SS undergoing repeated B lymphocyte depletion courses with RTX have been described. Aim of this study was to assess safety and efficacy of repeated B-cell depletion with RTX in patients with primary SS.

Methods: Out of an inception cohort of 378 patients (AECG 2002) we selected those subjects who had been treated with multiple courses of RTX on the basis of disease activity and/or lymphoproliferative complications. In addition to patients’ demographics, clinical and serological features, we retrieved the following information: indication for RTX therapy, previous and concomitant treatments, number of RTX courses, regimens, time to re-treatment, changes in the ESSDAI, in lab and serology tests and adverse events.

Results: Out of 17 SS patients who had been treated with RTX, we identified 5 female who had received repeated B lymphocyte depletion therapy. Patients had median age of 60 years (range31-65) and median disease duration of 36 months (range 12-120). All the patients were positive for antinuclear antibodies, anti-Ro/SSA and Rheumatoid Factor (RF); 2/5 (40%) had also a positivity for anti-La/SSB and cryoglobulins. HCV antibody test resulted negative in all patients. Initial indications for RTX included:  MALT  non-Hodgkin’s lymphoma (NHL) (3/5 ), central and peripheral nervous involvement  (pns)(1/5) and diffuse skin vasculitis (1/5). Three patients received 2 cycles of RTX, 1 received 3 cycles and 1 received 4 cycles. Indications for re-treatment included: MALT lymphoma recurrence (1/5) and/or increased disease activity in the other  cases. Median ESSDAI before RTX re-treatment was 11 (range 6-13) with patients presenting mainly enlargement of major salivary glands, reactive lymphoadenopathy, skin vasculitis, neuropathy and glomerulonephritis. Moreover, all patients presented low C3/C4 levels, and/or hypergammaglobulinemia and/or cryoglobulins. Three patients presented a high titer of RF and 2/5 had  a moderate lymphopenia. Each course consisted of 1 g  RTX intravenous (IV) on days 1 and 15 or 375 mg/m2 IV once weekly for 4 doses. Median interval between courses was 9 months (range 8-48). Multiple courses of RTX resulted in significant improvement of the ESSDAI and IgG levels compared with baseline (p<0.05). Despite not statistically significant, we also observed beneficial effects on C3, C4, RF and ESR. Retreatment with RTX was well-tolerated. None of the patients developed mild serum-sickness-like disease.  Infectious events included: recurrent urinary tract infection (2/5), skin infection (1/5) and Herpes Zoster reactivation (1/5).  Falls in total Ig levels occurred in one patient requiring Ig replacement therapy. 

Conclusion: Repeated B-lymphocyte depletion over a median 36-months period appears to be an acceptable and relatively well-tolerated therapy in SS. Further studies are needed to investigate optimal indications and timing  of retreatment of RTX in SS patients.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/repeated-b-lymphocyte-depletion-therapy-with-rituximab-in-sjogrens-syndrome-a-single-center-experience/