Alemtuzumab was designed to reduce the immunogenicity of the parent CD52-specific rat immunoglobulin. Although originally marketed for use in cancer (Mabcampath ® ), alemtuzumab is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada ® ). Perhaps due to its history as the first humanized antibody, the potential of immunogenicity of the molecule has been considered inconsequential, and anti-drug antibodies (ADA) responses were similarly reported as being clinically insignificant. Nonetheless, despite humanization and depletion of peripheral T and B cells, alemtuzumab probably generates the highest frequency of binding and neutralizing ADA of all humanized antibodies currently in clinical use, and they occur rapidly in a large majority of people with MS (pwMS) on alemtuzumab treatment. These ADA appear to be an inherent issue of the biology of the molecule-and more importantly, the target-such that avoidance of immunogenicity-related effects has been facilitated by the dosing schedule used in clinical practice. At the population level this enables the drug to work in most pwMS, but in some individuals, as we show here, antibody neutralization appears to be sufficiently severe to reduce efficacy and allow disease breakthrough. It is therefore imperative that efficacy of lymphocyte depletion and the anti-drug response is monitored in people requiring additional cycles of treatment, notably following disease breakthrough. This may help inform whether to re-treat or to switch to another disease-modifying treatment.

Background Cognitive impairment in people with multiple sclerosis (pwMS) negatively impacts daily function and quality of life (QoL). Prior studies of cognitive rehabilitation in pwMS have shown limited benefit but many focused on cognitive function scores rather than QoL measures. Studies using QoL metrics primarily evaluated group cognitive rehabilitation, which may be less appropriate due to variable cognitive profiles in pwMS. This study assesses the impact of an individualized cognitive rehabilitation approach on QoL in MS. Methods We performed a retrospective chart review of NeuroQoL assessments done by pwMS (n = 12, mean age 47.9 ± 4.0 years, 75% female, 100% White, 75% RRMS) before and after participation in an individualized compensatory cognitive program. We used a comparison group of pwMS who were candidates for the program but did not participate (n = 9, mean age 48.9 ± 4.4 years, 88.9% female, 100% White, 66.7% RRMS) Results PwMS who participated in the rehabilitation program saw improvements in Sleep Disturbance (50.5 from 55.5, p = 0.005), Fatigue (52.5 from 57.0, p = 0.024), Anxiety (49.8 from 55.4, p = 0.011), and Cognitive Function (39.3 from 36.7, p = 0.049). Conclusions Individualized compensatory cognitive rehabilitation appears effective for improving QoL measures in pwMS with cognitive complaints, supporting the need for further randomized controlled prospective analysis of this intervention.

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Background: The costs of multiple sclerosis (MS) disease-modifying therapies (DMTs) and certain symptomatic treatments (ie, dalfampridine [DFP]) are high. Consolidated billing models require that medication costs be covered by skilled nursing facilities (SNFs) after hospitalization. As a result, patients may experience suboptimal discharge, off of medication or without rehabilitation. Methods: To characterize the frequency with which MS pharmaceutical costs lead to suboptimal discharge, we performed a retrospective chart review of admissions to a large academic medical center from January 2013 to December 2017 among patients with MS on DMT and/or DFP with SNF rehabilitation recommendations. We quantified the burden of suboptimal discharge due to medication discontinuation, limited medication supplies, or forgone rehabilitation. Results: Among 169 admissions of patients with MS with discharge recommendations for SNF rehabilitation, there were 57 (33.7%) admissions across 49 patients with MS on DMT/DFP. Overall, 39 (68%) of 57 admissions (71% of patients) experienced a suboptimal discharge. Overall, 29 (65%) discontinued DMT/DFP, 9 (16%) took their remaining home supply of medications during rehabilitation (including 5 admissions also affected by a discontinuation), and 6 (11%) were discharged home to remain on DMT. Among those discharged to rehabilitation, discharge to a hospital-owned SNF was associated with a routine discharge with no lapse in medication (n = 11/15 vs 7/36, P < .001). Conclusions: High costs of MS medications in conjunction with SNF consolidated payment models result in misaligned incentives and often lead to medication discontinuation or other suboptimal discharge for patients with MS.