RESUMO
Background and objectives: Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants ('alemtuzumab-only') could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab ('IFN-alemtuzumab'). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5-7 years (11-13 years after alemtuzumab/IFN initiation). Methods: Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening [CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0], and 6-month confirmed disease improvement [CDI; >1.0-point EDSS decrease (baseline score ⩾2.0)]. Results: 43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3-13 for the alemtuzumab-only [0.17; 95% confidence interval (CI) 0.15-0.20] and IFN-alemtuzumab (0.14; 0.11-0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent. Conclusion: Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11-13 years, and most participants did not require more than one additional course. Clinicaltrialsgov identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656.
RESUMO
Background: Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life. Objective: To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy. Methods: This 24-month, prospective, multicenter, observational study had a primary endpoint of change in overall satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Secondary endpoints included the Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified Fatigue Impact Scale-5 (MFIS-5), and the Patient-Determined Disease Steps (PDDS). Safety was monitored with adverse events (AEs). Results: Of 199 enrolled patients, improvements were observed in mean TSQM scores for overall satisfaction (baseline, 50.3; year 2, + 13.2; p < 0.0001), effectiveness (49.3 and + 12.2; p < 0.0001), and side effects (77.6 and + 4.5; p = 0.04). Improvements were also observed in MSIS-29 physical (52.4 and -6.0; p < 0.0001), MSIS-29 psychological (53.4 and -7.0; p = 0.0003), and MFIS-5 (12.8 and -1.7; p < 0.0001). Most (95.0%) patients experienced ≥ 1 AE (88.4% mild, 67.8% moderate). Conclusions: The primary endpoint was met; the safety of alemtuzumab was consistent with pivotal studies.