Improvement in Cognitive Processing Speed With Ofatumumab in Patients With Relapsing Multiple Sclerosis
Ralph Benedict1, Iris Katharina Penner2, Gary Cutter3, Ludwig Kappos4, Patricia Coyle5, Daniela Piani-Meier6, Amin Azmon6, Ibolya Boer6, Wendy Su7, Jeffrey Cohen8
1Department of Neurology, Department of Neurology, University At Buffalo, 2Medical Faculty, Department of Neurology, Heinrich Heine University, COGITO Center for Applied Neurocognition and Neuropsychological Research, 3UAB School of Public Health, 4Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, 5Department of Neurology, SUNY At Stony Brook, 6Novartis Pharma AG, 7Novartis Pharmaceuticals Corporation, 8Department of Neurology, Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic
Objective:
To examine the effect of ofatumumab on cognitive processing speed (CPS).
Background:
In the phase 3 ASCLEPIOS I/II (NCT02792218/NCT02792231) trials, ofatumumab significantly reduced inflammatory disease activity and relapses, as well as delayed disability worsening, in patients with relapsing multiple sclerosis (RMS).
Design/Methods:
We analyzed the change in Symbol Digit Modalities Test (SDMT) score (baseline to Month 24; derived from a mixed model for repeated measures), proportion of patients with ≥4-point sustained improvement on SDMT (by categorical analysis), and time to first 6-month confirmed cognitive improvement (6mCCI; ≥4-point improvement on SDMT) in the overall population and in a subgroup of recently diagnosed (RD; within the last 3 years) patients. Time to first 6mCCI was analyzed in a subgroup with/without (SDMT score ≤43 or >43) baseline cognitive impairment.
Results:
Ofatumumab significantly improved SDMT scores from baseline to Month 24 vs teriflunomide in both the overall (n=492 with ofatumumab; n=468 with teriflunomide; mean age, 38.2 years) and RD populations (n=245 with ofatumumab; n=238 with teriflunomide; mean age, 35.9 years). Mean (SE) SDMT change from baseline was 3.50 (0.358) with ofatumumab and 2.39 (0.365) with teriflunomide in the overall population (p=0.030); these values were 4.29 (0.489) and 2.56 (0.492), respectively, in the RD population (p=0.012). The percentage of patients with ≥4-point sustained SDMT improvement was 25.0% (233/946) with ofatumumab and 19.6% (180/936) with teriflunomide in the overall population (p=0.005); these values were 26.9% (118/443) and 20.2% (91/454), respectively, in the RD population (p=0.018). Ofatumumab numerically increased the probability of time to first 6mCCI (hazard ratio [95% CI]) in the overall population (1.14 [0.96-1.36]), RD subgroup (1.19 [0.93-1.52]), and patients without baseline cognitive impairment (1.23 [0.98-1.56]).
Conclusions:
Ofatumumab was associated with more clinically meaningful improvements in CPS vs teriflunomide in both populations. Early initiation of ofatumumab may enhance CPS improvement in patients with RMS by suppressing inflammation.