Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis

Abstract

Objective: To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.

Methods: 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. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.

Results: We 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.

Conclusion: We 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 evidence: This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Thyroid Disease After Therapy Start and Proportion of Patients Not Starting a New Therapy

Kaplan-Meier plots of (A) proportion of patients without thyroid disease after therapy start and (B) proportion of patients not starting a new therapy. Patients with thyroid disease before therapy start were censored. Reference group comprised the noninduction therapies natalizumab, dimethyl fumarate, rituximab, and fingolimod, matched 10:1 to the alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) groups on age, sex, and region. DMT = disease-modifying therapy.

Figure 2. Infections, Drug Prescriptions, and Time Spent in Inpatient Care Before and After Therapy Start

Incidence rate (events per month) of (A) diagnosed infection and (B) prescription of drugs and (C) the proportion of time spent in inpatient care in 3-month intervals 3 years before and after therapy start. Patients were not censored at an event and continued to contribute person-time. Reference group comprised the noninduction therapies natalizumab, dimethyl fumarate, rituximab, and fingolimod, matched 10:1 to the alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) groups on age, sex, and region. DMT = disease-modifying therapy.