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Neurology Publish Ahead of Print DOI: 10.1212/WNL.0000000000011545
Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Non-induction Therapies for Multiple Sclerosis
Peter Alping MD,1,2 Joachim Burman MD,3 Jan Lycke MD,4 Thomas Frisell PhD,2 and Fredrik Piehl MD1,5 1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 3. Department of Neuroscience, Uppsala University, Uppsala, Sweden 4. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden 5. Academic Specialist Centre, Stockholm Health Services, Stockholm, Sweden
Abstract
Objective: To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT), compared to non-induction disease-modifying therapies.
Methods: We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national healthcare registers. Alemtuzumab, AHSCT, and a matched reference group of non-induction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, non-thyroid autoimmune disease, and infection.
Results: We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% Cy/ATG, 32% BEAM/ATG) patients, together with 2486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1000 person years=8.6, 95% confidence interval [CI]=2.3–22.0) compared to one patient in the AHSCT group (IR=1.7, 95% CI=0.0–9.6) and a mortality rate in the reference group of 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 non-thyroid 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 also AHSCT-treated patients, and found a higher incidence of infection for AHSCT, compared to both alemtuzumab and non-induction therapies. The incidence of non-thyroid 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
Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Non-induction Therapies for Multiple Sclerosis
Peter Alping MD,1,2 Joachim Burman MD,3 Jan Lycke MD,4 Thomas Frisell PhD,2 and Fredrik Piehl MD1,5 1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 3. Department of Neuroscience, Uppsala University, Uppsala, Sweden 4. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden 5. Academic Specialist Centre, Stockholm Health Services, Stockholm, Sweden
Abstract
Objective: To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT), compared to non-induction disease-modifying therapies.
Methods: We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national healthcare registers. Alemtuzumab, AHSCT, and a matched reference group of non-induction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, non-thyroid autoimmune disease, and infection.
Results: We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% Cy/ATG, 32% BEAM/ATG) patients, together with 2486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1000 person years=8.6, 95% confidence interval [CI]=2.3–22.0) compared to one patient in the AHSCT group (IR=1.7, 95% CI=0.0–9.6) and a mortality rate in the reference group of 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 non-thyroid 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 also AHSCT-treated patients, and found a higher incidence of infection for AHSCT, compared to both alemtuzumab and non-induction therapies. The incidence of non-thyroid 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