Background/Purpose: Among patients with auto-immune diseases (AID) treated with Rituximab (RTX), anti-drug antibodies (ADAb) leading to inefficacy and infusion reactions (Wincup and al., Ann Rheum Dis, 2019) is a frequent complication. We previously showed that it was more common in systemic AID than in RA (Combier and al, Rheumatology, 2020) In these conditions, targeting B cells with another anti-CD20 molecule is the only option. Obinutuzumab (OBZ) is an anti-CD20 humanized antibody frequently used in hematological malignancies. However, only few studies reported its efficacy and safety on a limited number of patients with autoimmune diseases, and never in the context of immunization against RTX. (Kvacskay and al., Ann Rheum Dis, 2022 ; Furie and al. Ann Rheum Dis, 2022). The presence of ADAb allows to hypothesize that targeting CD20 can still be efficacious with another molecule to which ADAb against RTX are not cross-reactive.

Methods: This study aims to describe efficacy and tolerance of consecutive patients with confirmed ADAb against rituximab and treated with OBZ between 2019 and 2023 in our tertiary department. Clinical and biological variables were collected before OBZ and 3 months after the first infusion. Response to OBZ was determined by the physician.

Results: Thirteen out of 15 were females (87%), with a median age of 53 years; 13/15 (87%) had Sjogren’s syndrome (SS). Among Sjögren patients 3/13 also had systemic lupus erythematosus (SLE), and 2/13 also had anti-synthetases syndrome. The remaining 2 patients did not have Sjogren’s and had eosinophilic granulomatosis with polyangiitis and mixed connective tissue disease.Thirteen out of 15 (87%) patients had been tested positively for anti-RTX antibodies. The most frequent symptoms leading to OBZ infusions were polyarthritis for 6/15 (40%) of them, cryoglobulinaemia for 3/15 (20%). The median duration from onset of the disease to first OBZ infusion was 9 years. The median number of cycles of RTX before OBZ was 2. Two patients had also received ofatumumab, another anti-CD20 therapeutic antibody. (Table 1). OBZ was well-tolerated in all patients without any infusion reaction even in patients with previous infusions reactions to RTX. Seven out of 15 (46%) patient presented with non-serious infections (Grade 1-2) mainly respiratory. Eight out of 15 patients (53%) had a clinical response to OBZ at 3 months. Comparing OBZ responders and non-responders at 3 months showed that responders trended to have longer disease duration (11 years vs 6, p=0.08). Number of treatment lines, co-treatments with corticosteroids or methotrexate were not different between groups.

Conclusion: In conclusion, obinutuzumab can be a good therapeutic option for AID patients who are immunized against RTX without symptomatic cross immunogenicity, with good tolerance and with clinical response in half of the patients. Further studies are required to determine which type of patients could respond to this treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/obinutuzumab-efficacy-and-tolerance-in-patients-with-auto-immune-diseases-immunized-against-rituximab/