Alemtuzumab Patient Reported Quality of Life: Recall Based Study of Experienced Subjects

Background: A cohort of alemtuzumab (ALE)-treated, refractory, high disability (EDSS 5.5-6.0  mean) MS patients has reported a favorable subjective experience. ALE provides improvement and/or temporary stabilization of EDSS in prior reports. How do these patients perceive their physical and mental experience with ALE?

Objectives: Retrospectively assess Patient Reported Outcome (PRO) changes after ALE of quality of life with SF-36 and a modified, retrospective SF-36 instrument

Methods: SF-36v2 is a standardized, validated, norm-based, instrument for collecting PRO perceptions of health. Both physical (PH) and mental health (MH) components are determined. Declines in health are decreases in the normalized scale; a norm of 50 with standard deviation (SD) of 10. We used both the SF-36v2 for current health status, and a novel, modified SF-36 which collects retrospective quality of life measures. This retrospective instrument queried ALE-experienced subjects regarding life experience in the two year epoch preceding ALE. The questionnaires were scheduled near entry to an open label phase I trial for ALE treatment (clinicaltrials.gov NCT01624714).  23 subjects had available data. The global question regarding health status was not collected retrospectively, but other items of the SF-36 were collected by recall for comparative purposes.

Results: At the time of first scheduled assessment, nearly all ALE-experienced subjects reported scores >=1 SD below norm for PH (21/23), but only a minority reported >= 1 SD below norm for MH (10/23). Measured as a change since first alemtuzumab cycle with retrospective recall, PH was improved in 48% of subjects; however, mean score was essentially unchanged (-3.1+/-1.5; 95% CI -0.1 to -6.1). This possibly correlates with the perceived need for additional ALE treatment and progressive disability of some in the cohort. However, 2/23 subjects reported dramatic PH improvements (18 and 20 points). MH improved in 70% (mean improvement 20.9+/-2.4; 95% CI 18.1 to 23.3); no subjects had major declines in MH but 9/23 reported major (>=1 SD) improvements.

Conclusions: Dramatic changes in SF36v2 scales are possible using this exploratory retrospective technique. In this high disability cohort, it is not surprising that recall over several years perceived little change in physical function. Indeed, function fluctuates in this cohort. Many participate in the trial due to wearing off of prior perceived beneficial ALE effects on disability. PRO stability of physical measures over years in a high disability population is encouraging. Significant improvement in perception of mental health was unexpected and apparent, and marked in magnitude in many subjects' recall. Serial data collection to assess the benefit of more regular ALE treatment and prospective changes in SF-36 should continue, and may be helpful in validating the retrospective collection of these data.