Alemtuzumab treatment in Denmark: A national study based on the Danish Multiple Sclerosis Registry

Abstract

Objective: To investigate clinical outcomes in a real-world setting in the complete population-based cohort of alemtuzumab-treated MS patients in Denmark. Methods: Data were retrieved from The Danish Multiple Sclerosis Registry between 2009 and 2019. Demographic and disease-specific patient parameters related to treatment history, efficacy, and safety outcomes were assessed at baseline and during follow-up visits. Results: A total of 209 patients (78% female) started treatment with alemtuzumab during the study period with 3.1 ± 1.4 years follow-up. After 2 years, 75% of patients were relapse-free compared to 48% the year before alemtuzumab ( p < 0.001). The annual number of relapses was reduced by 69% in year 4 compared with the year prior alemtuzumab. More active disease before alemtuzumab increased the annual hazard rate for relapse (HR: 2.88, p < 0.001). The Expanded Disability Status Scale (EDSS) score remained stable or improved in 81% of patients after 2 years. The need for an additional treatment course was associated with higher number of relapses in the year before alemtuzumab (odds ratio (OR) = 1.95, p = 0.001). Conclusion: In a country with primarily escalation strategy, relapse rate reduction was maintained for 5 years, and EDSS stabilized/improved in majority of patients. Higher relapse rate 1 year before alemtuzumab increased the odds for additional courses. Novel serious AEs were not observed.

Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis

“…This is slightly higher compared to previous studies, specifically 39% in one study where alemtuzumab was the first line treatment (Cohen et al, 2012;Coles et al, 2011) and 32% with alemtuzumab as the second line treatment (Center et al, 2012). Another study reported that EDSS remained stable in 68% of patients, and 75% of patients were relapse-free at two years, but did not report the combined NEDA status (Theodorsdottir et al, 2021). Finally, one study found that 80% stayed free from relapses and 93% stayed free from disability accumulation at two years (Kalincik et al, 2017).…”

“…Between 2009 and 2019, only 167 RRMS patients in Denmark received alemtuzumab for ≥2 year. (Theodorsdottir et al, 2021). Previous studies have included more patients (29 patients (Gilmore et al, 2020), 85 (Harding et al, 2019), 189 (Kalincik et al, 2017), 215 (Coles et al, 2011)), but implementation of article 20 from the European Medical Agency restricted the use of alemtuzumab (European Medicines Agency, 2019), and consequently the pool of potential patients for the study resulted in reduced recruitment.…”

Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents

“…It was shown that patients switching from fingolimod to ocrelizumab were more likely to experience suboptimal disease control and worsening of disability throughout the washout period and during a follow-up period of 6 month [38][39][40]. Use of alemtuzumab as successor to fingolimod was repeatedly debated [28][29][30][31][32][33][34][35][36]. However, a large prospective cohort study confirmed impaired effectiveness and safety of this therapeutic switch [37].…”

“…Other qualitative changes in the immune network that may influence disease activity include transcriptomic changes of CD4 + T cells [61], the modulation of T helper cell phenotype balances and the increase in regulatory T cell abundance [62]. We speculate that these effects interfere with cell depletion and immune reconstitution in an unfavorable manner, resulting in increased risk for progression of disability [24,25,[28][29][30][36][37][38][39][40] and, perhaps in part, the development of secondary autoimmunity [37].…”

“…Subsequently, several studies were conducted to assess the efficacy of alemtuzumab in patients previously treated with fingolimod, with conflicting results. While four retrospective analyses [31][32][33][34] and one small prospective study [35] demonstrated good effectiveness of alemtuzumab following fingolimod, a Danish prospective registry study showed that patients previously exposed to fingolimod are more likely to require a third course of alemtuzumab due to ongoing disease activity compared to other compounds [36].…”