Abstract
ObjectiveTo assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.MethodsWe performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.ResultsWe identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclophosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3–22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0–9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3–1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75–154) but also occurred more often for AHSCT (IR 34, 95% CI 18–56) compared to the reference (IR 5.3 95% CI 3.9–7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed ≥6 months from therapy initiation was 53 (95% CI 30–87) for alemtuzumab, 108 (95% CI 75–150) for AHSCT, and 51 (95% CI 46–57) for the reference.ConclusionWe confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.Classification of EvidenceThis study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.
Highlights
We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers
Four patients in the alemtuzumab group died compared to 1 patient in the autologous hematopoietic stem cell transplantation (AHSCT) group (IR 1.7, 95% confidence intervals (CIs) 0.0–9.6), and the mortality rate in the reference group was 0.7
Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75–154) and occurred more often for AHSCT (IR 34, 95% CI 18–56) compared to the reference (IR 5.3 95% CI 3.9–7.1)
Summary
We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. We performed a nationwide register-based cohort study of alemtuzumab and AHSCT compared to matched noninduction therapies, linking data from the Swedish MS register to national health care and demographic registers. The MS register was linked to several national registers with compulsory participation: the cause of death register, the patient register (all visits to inpatient and specialized outpatient care and their associated diagnosis codes, with high validity),[7] the prescribed drug register (complete data on all prescription drugs collected at pharmacies),[8] the cancer register,[9] demographic registers, and registers with data on sick leave and disability pension. Patients were excluded if they were
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