An analysis of patients in the German MS Register has found that 83% of real-world patients would not have met inclusion/exclusion criteria for entry in a trial of disease-modifying therapies (Jalusic et al. Mult Scler 2021; epublished January 20, 2021).
The database included 3577 patients with CIS, RRMS or SPMS; mean age was 39.68 years (range 15-76), mean EDSS score was 2.06, and the mean number of relapses in the preceding two years was 0.40. All disease-modifying therapies (DMT) were assessed except for siponimod and ofatumumab.
Overall, only 16.6% of patients met all the criteria for inclusion in a phase III clinical trial of the treatment they were taking. Only 4.0% of interferon-treated patients, 7.6% of ocrelizumab-treated patients and 12.0% of cladribine-treated patients met the entry criteria for their respective clinical trials. The largest proportion of patients meeting trial criteria was the fingolimod group (27.7%).
The relapse criterion used in trials, typically >1 relapse in the previous year or >2 relapses in the previous two years, was not met in 74.7% of real-world patients. If this criterion were not applied, two-thirds of patients would have met all other criteria. The proportion of patients meeting all other criteria ranged from 39.5% for ocrelizumab and 41.2% for cladribine, up to 76.5% for alemtuzumab and 84.7% for fingolimod.
In addition, the criteria for age (typically 18-55 years) and medication history (including washout) were common reasons for not meeting inclusion/exclusion criteria. The authors noted that regulators may require more heterogeneous trial populations in the future, although this would likely require large sample sizes. Trialists could also use registry data to guide patient selection so that results are more generalizable to real-world patients.