Effect of alemtuzumab on fatigue, quality of life, and patient/caregiver-reported outcomes in relapsing-remitting multiple sclerosis-A real-world evidence study

Background: Alemtuzumab is approved in the European Union for treating highly active relapsing-remitting multiple sclerosis (RRMS). Patient-reported outcomes measure the treatment impact on quality of life (QoL), including fatigue, a common symptom in multiple sclerosis (MS). Chronic diseases like MS also affect the patient's caregiver. Thus, understanding the impact on both patients and caregivers is essential for a comprehensive view of MS treatment outcomes. Methods: This multi-center prospective, observational study assessed RRMS patients undergoing alemtuzumab treatment, and their caregivers across three European countries (Denmark, Norway, and Italy). The study visits were conducted at baseline, and at Months 3, 6, 12, 18, 24, and 36 (± 1 month). The primary endpoint assessed the effect of alemtuzumab on MS-related fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC] score). Secondary endpoints included changes in cognition (Symbol Digit Modalities Test [SDMT]), depression (Beck Depression Inventory-Version II [BDI-II]), QoL (29-item Multiple Sclerosis Impact Scale [MSIS-29]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), working capacity/daily life activity (Health-Related Productivity Questionnaire [HRPQ]), and clinical evaluation (number of relapses, improvement in Expanded Disability Status Scale [EDSS] score, and need for re-treatment with alemtuzumab/any other treatment). Exploratory endpoints included caregiver perception of patient's QoL, caregiver QoL, and caregiver burden. The sample size (N = 80) was determined based on the 2-sided t-test at 5 % significance level. Data were analyzed descriptively. Safety was also evaluated. Results: Of 87 enrolled patients, 72.4 % (n = 63) completed all follow-ups. Significant improvement was observed in fatigue (p < 0.01), with a median (min, max) FSMC score change of -7.3 (-56.0, 34.0) units at the end-of-study (EOS), and clinically relevant improvement (≥ 9 units) noted in approximately 12.5 months. SDMT (3-5 units, p<0.05), BDI-II (median score of 9.5, i.e., no depression, p<0.01), and MSIS-29 (median change in physical and psychological impact scores -9.2, p < 0.01 and -14.8, p < 0.001, respectively) improved significantly from baseline to EOS. Global treatment satisfaction (p < 0.001), effectiveness (p < 0.05), and side effects (p < 0.05) significant improved exept at EOS, whereas treatment convenience remained same throughout the study. The percentage of patients with at least one relapse was similar each year of the study (10.8-13.2 %). A statistically significant improvement (p < 0.05) in EDSS was reported over time. At EOS, 4.5 % patients needed retreatment with alemtuzumab. Caregivers also reported improvement in patients' QoL over time, but the median change from baseline (physical and psychological impact scores:10.0 and -14.8, respectively) was not statistically significant (p > 0.05). Caregivers reported similar QoL and caregiver burden at baseline and EOS, apart from an increase in emotional QoL. Headache (51.2 %), pyrexia (44.2 %), and rash (34.9 %) were the most common adverse events (AEs). Majority of the AEs were either mild or moderate, apart from 25 severe AEs. Three patients discontinued prematurely, of which one patient died of sepsis related to treatment. Conclusion: This real-world study showed beneficial impact of alemtuzumab on fatigue, cognition, depression, QoL, and treatment satisfaction. Improvement in patient disability, and caregiver-reported outcomes indicated enhanced patients' QoL.