Endocrine Abstracts

Introduction: immune reconstitution therapies, which include cell-depleting monoclonal antibodies targeting CD20+ (ocrelizumab) or CD52+ (alemtuzumab) leukocytes, are approved for the treatment of multiple sclerosis. Autoimmune thyroid disease is the most common adverse effect of 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 presentation: A 41-year-old Caucasian man with primary progressive multiple sclerosis was started on ocrelizumab in July 2021, after the finding of active disease on MRI and progression of neurological symptoms. The patient had a family history of autoimmune thyroiditis. He was non-smoker, not overweight (BMI 24.5 kg/m²), and treated with lamivudine for chronic hepatitis B and baclofen. There were two previous findings of impaired fasting glucose. In January 2022, before the second ocrelizumab administration, the urine test showed glycosuria (>1000 mg/dl) and proteinuria, without ketonuria. In the last few weeks, the patient had reported polyuria and polydipsia, but no blurred vision or weight loss. HbA1c and blood glucose level confirmed the diagnosis of diabetes mellitus (87 mmol/mol and 442 mg/dl, respectively). The patient underwent further tests to clarify the etiology of hyperglycemia. GADA, IA-2A and ICA were found negative; C-peptide indicated a well-preserved beta-cell function (2.7 ng/ml). Renal and liver function were normal. Other autoantibodies related to endocrine diseases, such as TPO-Ab and ACA, were found negative. We started a strict glucose monitoring and basal-bolus insulin treatment (total daily dose 58 IU, 0.75 IU/Kg). Down-titration of insulin dosage had been progressive and relatively rapid: 43 IU after two weeks, 36 IU after the first month, 24 IU after six weeks. We added metformin 1000 mg and, after four months, insulin treatment has been permanently discontinued. The patient continued ocrelizumab treatment, but severe hyperglycemia has no longer occurred. In August 2023, the blood test showed a HbA1c level of 39 mmol/mol, indicative of an optimal glycemic control with only 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 defined as an ‘immune reconstitution syndrome’; nevertheless, cell depletion induced by ocrelizumab shows some differences in duration and cell population affected. This case suggests the need for screening and follow-up of glycemic status in patients treated with this monoclonal antibody. Further investigation is required to elucidate the correlation between hyperglycemia and ocrelizumab.