Endocrine Abstracts

Aim: Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing–remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ and subsequently the clinical outcome of AITD post-ALZ in patients who received ocrelizumab.

Patients and methods: We evaluated 36 RRMS patients treated with ALZ; of which 3 patients subsequently received ocrelizumab. Clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 55.5 months.

Results: Nineteen out of 32 patients (59.4%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.7 ± 11 (SD) months after the first ALZ cycle. The incidence of AITD and during the first year of follow-up was 18.8%, and 50% after the second ALZ course. Ten patients developed Graves’ disease (GD), one developed hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) and eight developed Hashimoto thyroiditis (HT), of which one developed hypothyroidism. The mean time to TRAb and anti-thyroglobulin (anti-Tg) and/or anti-thyroperoxidase (anti-TPO) antibody positivity onset from the first ALZ infusion was 24.8 ± 8.1 months and 18.1±12.7 months, respectively. Seven of ten (70%) GD patients showed a fluctuating course of hyperthyroidism-hypothyroirdism. All GD patients commenced antithyroid drugs (ATDs); six continued on ‘block and replace’ treatment; one required radioactive iodine and one total thyroidectomy. Five patients developed mild Graves’ ophthalmopathy. Remission was reported in four out of ten GD patients (40%); one spontaneously and three after ocrelizumab treatment with a mean time of 31.5±11.7 months. No significant relationship of AITD with age at the time of ALZ treatment, sex, smoking status, previous DMTs, positive baseline anti-TPO/anti-Tg antibodies and family history of AITD was found. Only in patients who were treated with fingolimod as last treatment before ALZ a trend for an increased incidence of TRAb positivity was reported (P=0.07). Two successful pregnancies were recorded: one with HT and hypothyroidism and the other with GD.

Conclusions: Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported. The majority of patients required prolonged ‘block and replace’ therapy in the minimum dose of each therapeutic agent or more definitive interventions. Treatment with ocrelizumab contributed in remission of GD.