番茄社区

No significant differences emerged in patient-reported outcomes among relapsing-remitting multiple sclerosis (MS) patients who received natalizumab (Tysabri) every 6 weeks (Q6W) versus every 4 weeks (Q4W), an analysis of data from the phase IIIb trial showed.

For both dosing groups, differences in least square mean (LSM) changes 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, in a poster presentation at the 2022 annual Consortium of Multiple Sclerosis Centers meeting.

These findings help clinicians understand patient perceptions of natalizumab Q6W versus Q4W dosing, especially in light of the effect, the researchers noted.

was designed to evaluate the efficacy of every-6-week natalizumab dosing based on the number of new or newly enlarging T2 hyperintense lesions at week 72. The study was prompted by earlier research that suggested a longer dosing interval might reduce the risk of progressive multifocal leukoencephalopathy (PML).

"PML remains a concern when utilizing high-efficacy therapeutic agents for multiple sclerosis," NOVA investigator John Foley, MD, of the Rocky Mountain MS Clinic in Salt Lake City, told 番茄社区.

"Dose extension of natalizumab was frequently utilized clinically following the publication of the TOUCH surveillance data suggesting a dynamic in PML without clear-cut trial evidence for maintained efficacy," he said. "On a clinical basis, it appeared that efficacy out to dose extension of 6 weeks was relatively well maintained."

"This phase IIIb trial provided significant evidence that this is the case," Foley noted. "Efficacy of natalizumab therapy was maintained with dose extension across multiple clinical and radiographic endpoints."

NOVA evaluated MS disease activity in patients who switched to Q6W after at least 1 year of disease stability on an every-4-week dosing schedule.

In their analysis, Ryerson and colleagues studied the NOVA modified intention-to-treat population, including 247 people in the Q6W group and 242 people in the Q4W group.

The researchers assessed responses on the Treatment Satisfaction Questionnaire for Medication (TSQM), Neurology Quality of Life (NQoL) fatigue questionnaire, Multiple Sclerosis Impact Scale (MSIS-29), EuroQol 5 Dimensions (EQ-5D-5L), and Clinical Global Impression (CGI)-improvement (physician and patient assessments) and CGI-severity rating scales (physician assessments).

Higher scores in TSQM, EQ-5D-5L, and CGI-improvement -- and lower scores in NQoL fatigue, 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 MSIS-29 physical, 10 points for MSIS-29 psychological, and at least 0.5 standard deviation in the EQ-5D-5L index score.

Differences in LSM change from baseline to week 72 for Q6W versus Q4W patients were not significant for patient-reported outcomes:

• TSQM: -1.00, P=0.410
• NQoL fatigue: 0.52, P=0.292
• MSIS-29 physical: 0.74, P=0.429
• MSIS-29 psychological: 0.67, P=0.572
• EQ-5D-5L: 0.00, P=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%), physician-reported CGI-improvement (72.1% and 70.1%), and physician-reported CGI-severity (45.3% and 47.1%).

However, in the Q6W group, 11.7% of physicians said CGI-severity scores were minimally worse and 4.9% said they were much worse at week 72, compared with 7.4% and 4.1%, respectively, in the Q4W group.

Odds ratio of improvement in CGI scores from baseline to week 72 for Q6W versus Q4W did not show meaningful differences between groups.

In NOVA, occurrence of adverse events and serious adverse events were 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 had no increased disability and remained classified as asymptomatic.

"Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab," NOVA researchers wrote.

Comment