Longer dosing intervals of natalizumab safe, effective for MS patients

Most patients with relapsing-remitting MS who are stable on natalizumab every 4 weeks, can switch to a 6-week dosing regimen without losing efficacy, according to results of a clinical trial published in the Lancet Neurology.

“Extension of the natalizumab dosing interval to longer than 4 weeks has been suggested as a possible means to reduce risk of progressive multifocal leukoencephalopathy, potentially by allowing limited CNS immune surveillance to return without the disease activity associated with treatment interruption,” John F. Foley, MD, of the Rocky Mountain MS Clinic in Salt Lake City, and colleagues wrote.

Foley and fellow researchers sought to assess the safety and efficacy of natalizumab administered once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting MS (RRMS).

The authors conducted a randomized, controlled, open-label, phase 3b trial at 89 MS centers in 11 countries, which included 499 participants, aged 18 to 60 years with RRMS, who had been treated with 300 mg of IV natalizumab once every 4 weeks with no relapses for at least 12 months before randomization and no missed doses in the previous 3 months.

Researchers randomly assigned participants on a 1:1 basis to switch to IV natalizumab once every 6 weeks (n = 251) or continue with once every 4 weeks (n = 248). The primary trial outcome was the number of new or newly enlarging T2 hyperintense lesions at week 72, which was assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse or neurological examination or efficacy assessment.

Researchers classified missing outcome data as primary estimands, which included all data, regardless of whether participants remained on the assigned treatment; and secondary estimands, which included all data obtained after treatment discontinuation or study withdrawal. Safety also was assessed in all participants who received at least one dose of study treatment.

Following adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0.20 (95% CI, 0.07-0.63) in the 6-week group and 0.05 (95% CI, 0.01-0.22) in the 4-week group (mean lesion ratio = 4.24; 95% CI, 0.86-20.85) under the primary estimand and 0.31 (95% CI, 0.12-0.82) and 0.06 [95% CI, 0.01-0.31; mean lesion ratio = 4.93 (95% CI, 1.05-23.2)] under the secondary estimand.

Adverse events occurred in 194 of 250 participants in the 6-week group and in 190 of 247 in the 4-week group, with serious adverse events occurring in 17 participants from each cohort. No deaths were reported.

“These results could provide important information for physicians who are making natalizumab treatment decisions and reinforce the need to balance these decisions with consideration of individual patient benefit and risk,” Foley and colleagues wrote.