Induction therapy that cause long-term cessation of disease-specific inflammation is an emerging treatment option for multiple sclerosis (MS). Alemtuzumab was the first induction-type therapy to be approved for relapsing-remitting MS (RRMS) in 2013/2014, while autologous hematopoietic stem cell transplantation (AHSCT) is an induction-type medical procedure which has been used to treat MS since 1995 and was approved for use in RRMS in Sweden in 2016.
This study aimed to assess safety outcomes for alemtuzumab and AHSCT, compared to non-induction disease-modifying therapies.
We performed a population-based cohort study linking the Swedish MS 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.
We identified 132 alemtuzumab and 139 AHSCT-treated patients, together with 2486 matched patients treated with non-induction 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 occurring ≥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.
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 infections for AHSCT compared to both alemtuzumab and non-induction therapies. Interestingly, the incidence of first-ever non-thyroid autoimmune events was similar between the groups. Disorders relating to reproductive organs and fertility were common in the AHSCT group, especially in females. Other adverse events were rare. Overall mortality was slightly higher in the alemtuzumab group, but only one of the four deaths was clearly linked to the treatment.