Higher Rates of Thyroid Disease in Alemtuzumab-Treated Patients With MS


Researchers also found that patients treated with autologous hematopoietic stem cell transplantation had higher rates of infection then other DMT-treated groups.

Peter Alping, PhD candidate, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Peter Alping, PhD candidate

A recent study investigated safety outcomes in alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) treatments for multiple sclerosis (MS) and found higher incidences of thyroid disease and infection when compared to patients treated with non-induction disease-modifying therapies (DMTs).

Patients treated with alemtuzumab had the highest incidence rate (IR) of thyroid disease (IR per 1000 person years, 109; 95% CI, 75-154). Patients treated with AHSCT also had a higher IR (IR, 34; 95% CI, 15-56) compared to reference patients treated with non-induction DMTs (IR, 5.3; 95% CI, 3.9-7.1).

First author Peter Alping, PhD candidate, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, and colleagues wrote that “in Sweden, alemtuzumab and AHSCT have primarily been used for aggressive RRMS or breakthrough inflammation on conventional therapies. Preference for either therapy has been driven mainly by local experience and availability. Widespread use of these therapies has been limited by concerns and uncertainty around their respective safety profiles in relation to other MS therapies.”

Alping and colleagues identified 132 patients treated with alemtuzumab and 139 patients treated with AHSCT from the nationwide MS registry. Of patients treated with AHSCT, 68% (n = 95) were on a high-dose cyclophosphamide and anti-thymocyte globulin (Cy/ATG) regimen while 32% (n = 44) were on a combination of four cytostatic agents (BCNU, etoposide, cytosine-arabinoside, and melphalan) and ATG (BEAM/ATG). 

A reference/control group of 2486 matched patients treated with non-induction DMTs were included. Non-induction DMTs used by the reference group were natalizumab (36%; n = 895), dimethyl fumarate (29%; n = 721), rituximab (22%; n = 547), and fingolimod (13%; n = 323).

READ MORE: Hematopoietic Stem Cell Implantation Prevents Disability Worsening in Patients With MS

First thyroid disease was diagnosed in 32 alemtuzumab and 14 AHSCT-treated patients. First non-thyroid autoimmune disease was rare and similar in all groups, with an IR of 3.0 (95% CI, 0.1-16.8) for alemtuzumab, 2.6 (95% CI, 0.1-14.5) for AHSCT, and 3.4 (95% CI, 2.3-4.9) for the reference group.

Infection occurred in 19 (14%) alemtuzumab and 66 (47%) AHSCT-treated patients. The IR for infection diagnosed past or at 6 months after 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 group. Herpes virus and bacterial sepsis were most common in AHSCT-treated patients, whereas infections were more heterogeneous in alemtuzumab-treated patients.

The alemtuzumab group had 4 (3%) deaths occur (IR, 8.6; 95% CI, 2.3-22.0): 2 suicides, 1 heart attack (occurred 1.4 years after therapy start), and 1 cytomegalovirus reactivation with multi-organ failure (occurred within 1 month of therapy). The AHSCT group had 1 death (IR, 1.7; 95% CI, 0.0-9.6), a suicide, and the reference group had a mortality rate of 0.7 (95% CI, 0.3-1.3).

A case of breast cancer and a case of urinary bladder cancer were recorded in the alemtuzumab group (IR, 5.4), while none were recorded in the AHSCT group. The reference group had an IR of 1.4. Female patients treated with AHSCT had an IR of 169 for diagnoses relating to reproductive organs and fertility compared to the reference IR of 33-38. This was more pronounced in the Cy/ATG subgroup (IR, 190).

Speaking to the efficacy of the induction therapies, Apling and colleagues found that the IR per 1000 person years for starting a new MS DMT was 26 (95% CI, 13-46) for alemtuzumab and 28 (95% CI, 16-47) for AHSCT, lower than the reference group IR of 134 (95% CI, 12-142). Patients with AHSCT that received the Cy/ATG conditioning regime had a higher rate of starting a new therapy than those that received the BEAM/ATG regime.

“In this observational study using high-quality data from clinical practice recorded in Sweden’s nationwide health registers, we investigated safety outcomes for all patients with MS in Sweden treated with alemtuzumab and AHSCT, compared to a reference group of matched non-induction MS DMTs. While the effectiveness of both alemtuzumab and AHSCT is considered high, safety concerns have limited their use and studies comparing safety outcomes across therapeutic options have so far been rare,” the authors wrote.

“Our main findings were a higher incidence of thyroid disease with alemtuzumab and to a lesser extent also AHSCT, a higher incidence of infection with AHSCT, and a low incidence of non-thyroid autoimmune disease for both therapies.”

Alping P, Burman J, Lycke J, Frisell T, Piehl F. Safety of alemtuzumab and autologous hematopoietic stem cell transplantation compared to non-induction therapies for multiple sclerosis. Neurology. Published online January 29, 2021. doi: 10.1212/WNL.0000000000011545
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