Obinutuzumab in systemic sclerosis: a multicentre retrospective case series
Roberto D'Alessandro, Stéphane Hilliquin, Emmanuel Chatelus, Grégory Pugnet, Marie-Elise Truchetet, Jérôme Avouac, Yannick AllanoreAbstract
Objective
To describe a real-life case series of patients with systemic sclerosis (SSc) treated with obinutuzumab (OBZ), a next-generation glycoengineered type II anti-CD20 monoclonal antibody, reporting for the first time its use in SSc.
Methods
We retrospectively collected clinical, laboratory, and instrumental data from five patients with SSc treated with OBZ. All patients were multi-refractory and previously treated by Rituximab (RTX), stopped in 4/5 cases because of allergic reactions. We reported safety data, immunological changes and clinical effectiveness. OBZ was administered at 1g on days 0 and 15, with maintenance infusions every 5–6 months.
Results
Patients were refractory to a median of five prior immunosuppressive therapies. At a median follow-up of 12 months, OBZ was well tolerated, without allergic cross-reaction or serious adverse events. Complete peripheral CD19+ B-cell depletion was achieved in all patients. Gamma-globulin levels decreased from a median of 11.7 to 8.8 g/L. Skin fibrosis improved, with median mRSS decreasing from 27 (range 4-31) to 8 (range 0-23). Articular remission was achieved in all assessable patients. Across 3 SSc-interstitial lung disease patients, lung parenchymal disease remained stable on functional assessment and imaging. Corticosteroid doses were reduced or stabilised in all patients, from a median of 10 mg (range 0-20) to 5 mg (range 0-10) per day.
Conclusions
OBZ may represent a valuable therapeutic option in SSc, particularly in patients with RTX intolerance or inadequate response. Meaningful clinical benefit was observed even in advanced, non-inflammatory phenotypes; whether deeper, tissue-level B-cell depletion contributes to this benefit remains a hypothesis to be investigated prospectively.