Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> In CARE-MS II (Comparison of Alemtuzumab and Rebif<jats:sup>®</jats:sup> Efficacy in Multiple Sclerosis; NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved health-related quality of life (HRQL) outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients over 2 years. Patients completing CARE-MS II could enter a 4-year extension study (NCT00930553). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> The aim of this study is to assess 6-year HRQL outcomes in alemtuzumab-treated CARE-MS II patients, including those with highly active disease (HAD). </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> During extension, patients could receive additional alemtuzumab for clinical/magnetic resonance imaging (MRI) activity or other disease-modifying therapies per investigator’s discretion. Assessments include Functional Assessment of Multiple Sclerosis (FAMS), 36-Item Short-Form Health Survey (SF-36), and EQ-5D visual analog scale (EQ-VAS). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Alemtuzumab-treated patients improved or stabilized all HRQL measures over 6 years with significant improvements from baseline at all time points on EQ-VAS and for up to 5 years on FAMS, SF-36 MCS, and SF-36 PCS. Alemtuzumab-treated patients with HAD showed significant improvements versus baseline at Year 2 on all HRQL measures, and significant improvements versus SC IFNB-1a on SF-36 PCS and EQ-VAS; however, the improvements did not reach the threshold for clinical relevance. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Alemtuzumab-treated CARE-MS II patients improved or stabilized HRQL versus baseline over 6 years. This is the first study to show long-term HRQL benefits in patients with HAD. </jats:p></jats:sec>

Quality of Life Improves with Alemtuzumab Over 6 Years in Relapsing-Remitting Multiple Sclerosis Patients with or without Autoimmune Thyroid Adverse Events: Post Hoc Analysis of the CARE-MS Studies

“…HRQL outcomes were similar in patients with nonserious thyroid AEs and those without thyroid AEs, indicating that nonserious thyroid AEs did not adversely affect patients' perceptions of their physical and mental health. Because the majority of patients had either no thyroid AEs or nonserious thyroid AEs, the magnitude of HRQL change in these subgroups is consistent with previous studies demonstrating HRQL improvement in the overall CARE-MS I and II populations after treatment with alemtuzumab, which stabilized over 6 years [7][8][9]. These HRQL findings likely reflect the efficacy of alemtuzumab, in which 78-81% of patients show stable or improved disability on the Expanded Disability Status Scale (EDSS) over 6 years [5,6].…”

“…Alemtuzumab significantly reduced relapses, disability, magnetic resonance imaging (MRI) lesions, and brain volume loss compared with subcutaneously administered interferon beta-1a (SC IFNB-1a) in the core studies, and alemtuzumab efficacy was maintained through year 6. In parallel with these clinical and MRI improvements, alemtuzumab-treated patients reported significantly greater HRQL improvements from baseline to year 2 compared with SC IFNB-1a-treated patients, and HRQL with alemtuzumab remained above baseline or similar to baseline through year 6 [7][8][9].…”

Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years

“…Worsened QoL in these patients was in contrast to the improved or stable QoL recently reported in the overall CARE-MS II population. 19 Results of this post hoc analysis must be interpreted with caution. Currently, no consensus diagnostic criteria exist for secondary progressive MS. We used an objective definition developed by an independent group, using functional system scores to increase diagnostic accuracy and a short confirmation period to reduce the period of diagnostic uncertainty while maintaining specificity.…”

“…In patients who converted to secondary progressive MS, further descriptive analyses in alemtuzumab-only patients included percentage of patients who received additional alemtuzumab and/or treatment with another DMT, reasons for additional alemtuzumab, temporal relationship between additional alemtuzumab courses and conversion to secondary progressive MS, efficacy endpoints (annualized relapse rate [ARR], mean EDSS score, and number of new gadolinium [Gd]-enhancing and new/enlarging T2 hyperintense lesions [also assessed for IFN-alemtuzumab]) by year over 6 years, and quality-of-life (QoL) assessments (Functional Assessment of Multiple Sclerosis [FAMS; version 4], 16 Short-Form-36 [version 2] physical component summary and mental component summary [SF-36 PCS and MCS], 17 and European Quality of Life-5 Dimensions Visual Analog Scale [EQ-VAS]) 18 from baseline to Year 6 (higher scores indicate better QoL on all instruments assessed; p values were based on Wilcoxon signed-rank test). 19 …”

“…In patients who converted to secondary progressive MS, further descriptive analyses in alemtuzumab-only patients included percentage of patients who received additional alemtuzumab and/or treatment with another DMT, reasons for additional alemtuzumab, temporal relationship between additional alemtuzumab courses and conversion to secondary progressive MS, efficacy endpoints ( 18 from baseline to Year 6 (higher scores indicate better QoL on all instruments assessed; p values were based on Wilcoxon signed-rank test). 19 Sensitivity analyses of the optimal definition from Lorscheider et al 6 in alemtuzumab-only patients included varying confirmation periods (6, 12, or 24 months) and an alternative threshold using a minimum EDSS score of 3 with confirmation periods of 3, 6, 12, or 24 months. Definitions using EDSS score 3 were found by Lorscheider et al to have lower specificity and lower overall accuracy than definitions using EDSS score 4 (particularly when using 6-month confirmation).…”