(A-327) The risk of mortality in patients with Multiple Sclerosis treated with alemtuzumab compared to other disease modifying therapies: A cohort study with data from five countries

Background: A European Commission Article 20 procedure in 2019 highlighted insufficient data on the risk of mortality in patients with multiple sclerosis (MS) treated with alemtuzumab.

Objectives: To ascertain whether MS patients treated with alemtuzumab had a higher risk of all-cause mortality than comparable MS patients treated with other highly efficacious disease modifying therapies (HE-DMTs).

Methods: This comparative cohort study was based on secondary use of data from routine health care settings in five countries: UK (chart review data from three academic clinical centres); Denmark, Sweden, Czech Republic (national MS registries); Germany (administrative claims data). MS patients initiating alemtuzumab or other HE-DMTs after the date of alemtuzumab approval/reimbursement in each country were included. Patients were followed from the date of initiation until the earliest of: death, last vital status update, emigration, end of insurance or end of data collection. The outcome was all-cause mortality. Crude mortality rates (CMR) were calculated. To address confounding by MS severity, propensity score weighting was used. The risk of death was modelled individually in each country using Cox Proportional Hazards (CPH) models.

Results: A total of 1,183 patients treated with alemtuzumab (ranging from 56 in Sweden to 457 in UK) and 27,573 HE-DMT patients (ranging from 503 in Czech Republic to 10,511 in Sweden) were included. Mean follow-up time was 5.7 years for the alemtuzumab cohort and 4.7 years for the comparator HE-DMT cohort. Considerable heterogeneity in demographic and clinical characteristics was observed across countries for alemtuzumab patients, driven by differences in local treatment guidelines. After PS weighting, covariate balance was not fully achieved. A low number of events was observed, ranging from 1 in Czech Republic to 7 in German data. The CMR for alemtuzumab ranged from 104 (UK) to 527.2 (Sweden) / 100,000 person years (PY). In the comparator HE-DMT cohort, between 0 (Czech Republic) and 153 (Sweden) were observed and the CMR ranged from 0 (Czech Republic) to 332 (Germany) / 100,000 PY. Due to low numbers of deaths in each country and violations of model assumptions, the CPH models were not interpretable.

Conclusions: This study provided insight into the heterogeneous prescribing patterns for alemtuzumab, the differences in underlying exposed populations across five European countries, and how these impacted the observed mortality rates. The study did not provide evidence for an increased risk of mortality in alemtuzumab treated patients.