Neurocognitive Function over 24 Months in Patients with RRMS Initiating Alemtuzumab in Routine Clinical Practice: LEM-COG Study Design

Background: An estimated 40%–75% of patients with MS suffer cognitive impairment, and cognitive dysfunction has been shown to correlate with brain atrophy. Disease-modifying therapies that reduce brain atrophy may thus have a positive impact on cognitive functioning. Alemtuzumab, a humanized anti-CD52 monoclonal antibody approved for the treatment of RRMS in >60 countries, significantly reduces MRI disease activity and the rate of brain volume loss (brain atrophy), and significantly increases the likelihood of sustained reduction of disability.

Objectives: To describe the design of the LEM-COG study, which will characterize changes in neurocognitive function, mood, fatigue, brain lesion burden, regional and global brain volume, and safety in RRMS patients treated with alemtuzumab in routine clinical practice.

Methods: LEM-COG is a 24-month, prospective, multicenter, observational study, enrolling approximately 150 patients aged 25–55 years with RRMS who have been prescribed alemtuzumab in routine clinical practice in the United States and Canada. Alemtuzumab 12 mg/day IV will be administered per approved labeling as 2 courses (baseline: on 5 consecutive days; Month 12: on 3 consecutive days). Primary endpoint: change in the Multiple Sclerosis Cognitive (MS-COG) composite score from baseline to 24 months. Secondary endpoints: change from baseline to 24 months in Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Brief Visuospatial Memory Test – Revised, Selective Reminding Test, Controlled Oral Word Association Test, Automated Neuropsychological Assessment Metrics composite score and individual test measures, Hamilton Rating Scale for Depression, Fatigue Severity Scale, and Modified Fatigue Impact Scale; and changes over time in T₁ and T₂ lesion volume, gadolinium-enhancing lesions, regional and global brain volume, and resting state functional MRI and myelin/axonal content. MRI data will be collected only at centers in which it is available and part of local standard practice. Patients will be evaluated at baseline, Month 12 (before second treatment course), and Month 24. Adverse events will be recorded. 

Results: LEM-COG is currently enrolling patients.

Conclusions: LEM-COG will provide important real-world insights into the impact of alemtuzumab on cognitive function, mood, fatigue, and MRI changes associated with RRMS.