No significant differences were seen in patient-reported outcomes between relapsing-remitting multiple sclerosis (MS) patients who received natalizumab (Tysabri) every 6 weeks (Q6W) versus every 4 weeks (Q4W), analysis of data from the Phase IIIb NOVA trial showed.
For the two dose groups, differences in changes in least square mean (LSM) in patient-reported outcomes from baseline to week 72 were small and comparable, said Lana Zhovtis Ryerson, MD, of NYU Langone Health in New York City. and colleagues, at the poster presentation at the 2022 Multiple Sclerosis Centers Consortium annual meeting.
The authors note that these findings help clinicians understand patient perceptions of natalizumab Q6W versus Q4W doses, especially in light of the erosive effect of natalizumab.
NOVA was designed to evaluate the efficacy of dosing natalizumab every 6 weeks based on the number of new or newly enlarged T2 hypertensive lesions at week 72. The study was conducted from previous research that suggested that a longer dosing period may reduce the risk of progressive multifocal leukoencephalopathy (PML). ).
“PML remains a concern when high-potency therapeutic agents are used for multiple sclerosis,” said NOVA investigator John Foley, of the Rocky Mountain MS Clinic in Salt Lake City. MedPage today.
“natalizumab dose extension has been used frequently clinically following the publication of TOUCH observational data indicating a reduced dynamic rate in PML without clear experimental evidence to maintain efficacy,” he said. “On a clinical basis, the efficacy of extending the dose to 6 weeks appears to have been relatively good.”
“This Phase IIIB trial has provided important evidence that this is the case,” Foley noted. “Efficacy of natalizumab therapy was maintained with dose extension across several clinical and radiographic end points.”
NOVA assessed MS activity in patients who switched to Q6W at least 1 year after disease stabilization on a 4-week dosing schedule.
In their analysis, Ryerson and colleagues studied a NOVA-adjusted intent-to-treat cohort, including 247 people in the Q6W group and 242 people in the Q4W group.
The researchers assessed responses to the Medication Treatment Satisfaction Questionnaire (TSQM), the Neurological Quality of Life Fatigue Questionnaire (NQoL), the Multiple Sclerosis Impact Scale (MSIS-29), the EuroQol 5 Dimensions (EQ-5D-5L), and clinical overall impression. (CGI) – improvement (doctor and patient rating) and CGI severity rating scales (doctor ratings).
Higher scores in TSQM improvement, EQ-5D-5L, and CGI—and lower scores in NQoL stress, MSIS-29, and CGI severity—indicated better outcomes. Clinically meaningful changes from baseline were defined as at least 5 points for NQoL fatigue, 7.5 points for physical MSIS-29, 10 points for psychological MSIS-29, and at least 0.5 standard deviation in the EQ-5D-5L index score .
Differences in LSM that did not change from baseline to week 72 for Q6W versus Q4W patients were not significant for patient-reported outcomes:
- TSQM: -1.00, s= 0.410
- Fatigue NQoL: 0.52, s= 0.292
- MSIS-29 physical: 0.74, s= 0.429
- MSIS-29 Psycho: 0.67, s= 0.572
- EQ-5D-5L: 0.00, s= 0.978
From baseline to week 72, most Q6W and Q4W scores showed no change in patient-reported CGI improvement (51.0% and 55.8%), clinician-reported CGI improvement (72.1% and 70.1%), and severity of patient-reported CGI. The doctor (45.3% and 47.1%).
However, in the Q6W group, 11.7% of clinicians said their CGI severity scores were somewhat worse, and 4.9% said they were significantly worse at week 72, compared to 7.4% and 4.1%, respectively, in the Q4W group.
The odds ratio of improvement in CGI scores from baseline to week 72 for Q6W versus Q4W did not show significant differences between groups.
In NOVA, the incidence of adverse events and serious adverse events was consistent in the Q4W and Q6W groups. There was one case of asymptomatic PML in the Q6W group and no cases of PML in the Q4W group. Six months after diagnosis, the participant with PML did not have increased disability and remained classified as asymptomatic.
“Although this trial was not effective for assessing differences in risk of PML, the occurrence of the condition (asymptomatic) underscores the importance of monitoring and consideration of the risk factor in all patients receiving natalizumab,” the Nova researchers wrote.
The NOVA study was funded by Biogen.
Ryerson reported personal compensation for advisory board activities from Biogen, Genentech and Novartis, and research support from Biogen, Celgene and Genentech.