麻豆传媒

LONDON -- Patients started on off-label rituximab had better drug survival than those given fingolimod (Gilenya) or natalizumab (Tysabri), Swedish researchers found.

There was a significantly greater likelihood of staying on rituximab compared with fingolimod or natalizumab over about 5 years (drug survival probability 0.9 versus 0.6 and 0.4) among patients tracked in the Swedish MS Registry, , of the Karolinska Institute, reported during a platform session at the here.

"Rituximab is a superior drug for RRMS patients when used either as first- or second-line therapy," Piehl said. "It was also superior to fingolimod for patients switching from natalizumab."

There are three anti-CD20 monoclonal antibodies of interest in MS: off-label rituximab, ocrelizumab (Ocrevus) under FDA review, and ofatumumab, which was .

Piehl noted that there have been no comparative effectiveness studies between any of the anti-CD20 drugs -- also known as B cell therapies -- and other highly effective MS therapies.

So he and his colleagues conducted a retrospective observational study of patients in the Swedish MS Registry, which included 5,580 therapy periods in 4,244 patients. Overall, 1,837 were on rituximab, 1,374 were on fingolimod, and 2,369 were on natalizumab.

The mean age was about 44, 69% were female, and 68% had relapsing remitting MS, 34% had secondary progressive MS, and 6% had primary progressive MS. The mean disease duration was 11.3 years, and the mean treatment duration was 21.1 months.

The better drug survival outcomes over 5 years seen with rituximab over fingolimod and natalizumab held when the results were analyzed by first- or second-line therapy (drug survival probability 0.9 versus 0.6 and 0.5 for both models), Piehl reported. They also had better relapse-free survival, he added.

Those who had to come off natalizumab because of JC-positive antibody status did better when they switched to rituximab compared with fingolimod (drug survival probability 0.9 versus 0.4), he reported.

Piehl said the study's strengths included the fact that it was national and population-based, but that it was limited by its retrospective, observational nature. The non-randomized design makes it sensitive to confounding by indication, Piehl warned.

Since patients on natalizumab were younger and had more severe disease at study entry, "based on our experience that would be a huge baseline factor and may explain the data we see here," Piehl said, noting that these were crude data that weren't controlled for confounders.

His team will conduct the prospective observational SWEEP-MS trial in collaboration with Kaiser Permanente Southern California, funded by the U.S. Patient Centered Outcomes Research Institute to assess the comparative safety of commonly used MS drugs.

, of Queen Mary University of London, noted that the National Health Service declined to approve rituximab off-label for the treatment of MS -- a problem experienced by some MS clinicians in the U.S. as well. The University of Colorado, for instance, has long run a rituximab program for MS patients that is covered -- but , of Ohio Health and Science University in Portland, Ore., said it's been a challenge to get insurers in that state to pay for the treatment.

Piehl noted that Biogen brought a formal complaint in Sweden against use of rituximab in MS, but that Swedish health councillors decided that off-label use of rituximab wasn't in violation of Swedish law.

Rituximab drugmaker Roche is preparing for a pending FDA decision on its newer anti-CD20 drug ocrelizumab, which has a PDUFA date of Dec. 28. Experts questioned here by 麻豆传媒 about whether they would switch their rituximab patients to ocrelizumab generally agreed that it depends on several factors, including patient characteristics and insurance coverage.

, of the University of Colorado at Denver, said that many patients who are stable on rituximab and have it covered by insurance will probably stay on that drug "unless the insurance company wants to pay more for on-label ocrelizumab."

"For new starts," he said, "the question will be, what does insurance pay for, as one will be cheaper but off-label."

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