After a previous analysis showed that natalizumab dosing every 6 weeks can decrease the risk of progressive multifocal leukoencephalopathy, new data showed no differences in patient-reported outcomes vs treatment every 4 weeks.
Exploratory data from the phase 3b NOVA study (NCT03689972) showed no significant or clinically meaningful differences in patient-reported outcomes (PRO) or Clinical Global Impression (CGI) rating scores among those with relapsing-remitting multiple sclerosis (MS) treated with natalizumab 300 mg (Tysabri; Biogen) every 4 weeks (Q4W)—the approved regimen—or every 6 weeks (Q6W).1
Led by Lana Z. Ryerson, MD, associate professor, NYU Langone, the analysis evaluated patients treated with natalizumab Q6W over 72 weeks who were previously treated with Q4W dosing for at least 12 months compared with continuation of Q4W dosing. The randomized, controlled, open-label, rater-blinded study looked at several PROs, including the Treatment Satisfaction Questionnaire for Medication (TSMQ), Neurology Quality of Life (NQoL) fatigue questionnaire, Multiple Sclerosis Impact Scale (MSIS-29), and EuroQol 5 Dimensions (EQ-5D-5L) index score.
Presented at the 2022 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, June 1-4, in National Harbor, Maryland, the study also used CGI-improvement and CGI-severity rating scales as part of the exploratory efficacy outcomes. Ryerson et al used a mixed model of repeated measures or ordinal logistic regression, adjusted for geographic region, baseline body weight, duration of natalizumab exposure at baseline, and respective baseline PRO score.
Between the Q6W (n = 247) and Q4W (n = 242) dosing groups, there were no significant differences in least-squares mean change from baseline to week 72 in PROs (TSQM: −1.00 [P = .410]; NQoL fatigue: 0.52 [P = .292]; MSIS-29 Physical: 0.74 [P = .429]; MSIS-29 Psychological: 0.67 [P = .572]; EQ-5D-5L: 0.00 [P = .978]). Similarly, the odds ratios (ORs) for CGI scores, specifically patient GCI-improvement (OR, 1.2; 95% CI, 0.80-1.73), physician GCI-improvement (OR, 0.8; 95% CI, 0.47-1.36), and physician CGI-severity (OR, 1.0; 95% CI, 0.71-1.54), were not meaningfully different between the dosing regimens.
The reasoning behind using a Q6W dosing regimen was based on previous findings, which suggested that a longer interval dosing may significantly reduce the risk of developing progressive multifocal leukoencephalopathy (PML). In that prior work, while studying each treatment arm, investigators observed a mean number of new or newly enlarging T2 hyperintense lesions at week 72 of 0.20 in the Q6W group compared with 0.05 in the Q4W group (P = .0755), showing no clinical significance. The higher lesion count in the Q6W group was largely attributed to a patient who developed lesions 3 months after discontinuing treatment and another who developed asymptomatic PML. The efficacy data coincided with an updated safety analysis of the Tysabri Outreach: Unified Commitment to Health (TOUCH) Prescribing Program which showed an 88% reduction in the probability of developing PML infection in the Q6W dosing group (HR, 0.118; P <.0001) when compared with the Q4W dosing regimen.2
The occurrence of adverse events (AEs) and serious adverse events were consistent in both the Q4W and Q6W treatment arms, confirming the existing safety profile for IV natalizumab. The patient in the Q6W arm who developed asymptomatic PML was at higher risk, according to investigators, with an anti-JC virus antibody index greater than 1.5 and over 2 years of natalizumab treatment.
At the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, MS expert Stephen Krieger, MD, sat down with NeurologyLive® to discuss the data from NOVA, including the significant findings on decreased PML risk.