Diabete mellito dopo trattamento con ocrelizumab per sclerosi multipla primariamente progressiva

Diabetes mellitus after ocrelizumab treatment for primary progressive multiple sclerosis

Objectives: immune reconstitution therapies, which include antibody-based cell-depleting therapies targeting CD20+ (ocrelizumab, ofatumumab) or CD52+ (alemtuzumab) leukocytes, are approved for the treatment of multiple sclerosis. Autoimmune thyroid disease is the most common adverse effect of treatment with alemtuzumab, but some cases of autoimmune diabetes have been reported. To date, diabetes mellitus has not been reported after CD20-targeting monoclonal antibodies therapy.
Case Report: a 41-year-old man with primary progressive multiple sclerosis was diagnosed with diabetes mellitus six months following the first ocrelizumab infusion. He experienced polyuria and polydipsia, but not other symptoms as visual loss or weight loss. We started a basal-bolus insulin therapy, with progressive and relatively rapid improvement of glycemic control. To note, C-peptide resulted indicative of a preserved beta-cell activity and autoantibodies were negative. To present date, the patient reached an excellent control with metformin.
Conclusions: this is the first case of diabetes mellitus reported after ocrelizumab administration. The timing of onset and course are similar to alemtuzumab-induced autoimmune diseases, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion appears inferior in duration and cell population affected. This case suggests the need for screening and follow-up of glycemic status in patients treated with ocrelizumab.
As a novel therapeutic antibody, further investigation is required to elucidate the correlation between hyperglycemia and ocrelizumab.