DALLAS – Persons with multiple sclerosis who had been taking natalizumab for at least 2 years and then switched to fingolimod or injectables such as interferon-beta or glatiramer acetate faced more disability than did their counterparts who continued on the drug, according to results from a retrospective study of patient-reported data.
"If people stopped natalizumab after 2 years, regardless of their risk of progressive multifocal leukoencephalopathy [PML], we wanted to know if their disease worsened," Stacey S. Cofield, Ph.D., said in an interview at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis. "What we have seen in a short follow-up time is that, yes, it does."
Dr. Stacey S. Cofield
Dr. Cofield is the deputy director of the North American Research Committee on Multiple Sclerosis (NARCOMS) in Birmingham, Ala., and is a faculty member in the biostatistics department at the University of Alabama, Birmingham.
To help close the gap of knowledge on clinical outcomes for patients who stop natalizumab (Tysabri) treatment, often due to an elevated risk for PML, Dr. Cofield and her associates reviewed outcomes as measured by the Patient-Determined Disease Steps (PDDS) scale. The PDDS is a validated, patient-reported scale of disease progression that runs from normal with a score of 0 to bedridden with a score of 8.
The investigators created three groups from a total of 547 patients who had undergone at least 2 years of continuous natalizumab treatment between 2005 and 2013 and had completed at least one follow-up survey that included a PDDS assessment: 406 whose only disease-modifying treatment during the time reviewed was natalizumab; 50 who switched to fingolimod (Gilenya) after at least 2 years of natalizumab; and 71 who switched to injectables after at least 2 years of natalizumab. A total of 10 patients who’d switched to other treatments, including exclusively symptomatic treatments, were not included in the study. The investigators also excluded another 10 patients who lacked PDDS assessments in the first survey during natalizumab treatment.
Patient characteristics across all three study groups at the start of their natalizumab treatment trended similarly: They tended to be white, female, have a median age of 50 years (P greater than .05 for all), and have similar baseline PDDS scores of between 3 and 4 (P = .1334). Roughly a third of each group reported having employment outside the home (P = .7104).
The median months of total follow-up were significantly different across the arms. For the natalizumab-only arm, the median range for follow-up was about 48 months; for fingolimod, it was 54 months; and for injectables, it was 60 months (P less than .0001).
Once patients had transitioned, Dr. Cofield reported, "the fingolimod switch had about 12 months of follow-up time. Patients stayed on natalizumab about 4 years before switching, on average." This was due, in part, to fingolimod not being available until 2010, leaving very little "capture time" for the window of data the investigators were reviewing, she said.
For the injectables group, the median follow-up time was 12 months.
Older age, male gender, and a lower baseline PDDS score were predictors of lower PDDS scores at follow-up (P less than .03 for all), but the total follow-up time was not (P = .69).
The adjusted mean PDDS score did not differ between the groups after 2 years of natalizumab therapy (P = .11); however, at the end of follow-up, the mean PDDS increase in the fingolimod group (0.58 points) and the injectables group (0.71) was significantly different from that of the natalizumab group (0.31; P = .007).
There was also a significant difference across the groups in the number of patients who had an increase in their PDDS score of at least 1 point: 31% for the natalizumab group, 46% for the fingolimod group, and 42.3% for the injectables group (P = .03).
"The mean change in the fingolimod group was slightly lower, but their group had a higher proportion with a 1 point increase," Dr. Cofield said. "So, the ones who switched to fingolimod either weren’t changing [their PDDS score] or were changing by one whole point."
"The take-away is that patients should be aware of the discussion they should be having with their physician after 2 years of treatment" with natalizumab, Dr. Cofield said in the interview. "Physicians can use this information to discuss the balance between the side effects and the risks of natalizumab, with the changes patients may see if they leave the treatment."