Baseline Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR) are the most important determinants of therapeutic lag among patients with multiple sclerosis (MS), according to study results published in Multiple Sclerosis.
Study researchers sought to investigate the relationships between MS characteristics and therapeutic lag on relapses and disease progression. To accomplish this, they pooled data from the MSBase registry, collected from 125 centers in 37 countries, and the Observatoire Français de la Sclérose en Plaques (OFSEP) registry, collected from 39 centers in France. They then stratified patients into disability progression (n=5415) and disease relapse (n=10,192) cohorts and assessed patients for EDSS and ARR.
Patients from the 2 registries were balanced for baseline characteristics, however, injectable therapy was more common among patients in MSBase (51.7% and 44.6%) than OFSEP (41.4% and 33.1%) among the progression and relapse cohorts, respectively.
Among the disability progression cohort, longer therapeutic lag was associated with men (mean, 55.8 weeks; 95% CI, 45.6-66.0), patients with EDSS scores of at least 6 (mean, 47.5 weeks; 95% CI, 23.7-71.3), and ARR of at least 1 (mean, 52.4 weeks; 95% CI, 38.9-65.9) compared with women (mean, 31.8 weeks; 95% CI, 26.2-37.5), patients with EDSS scores less than 6 (mean, 17.2 weeks; 95% CI, 13.6-20.5), or those with ARR less than 1 (mean, 29.2 weeks; 95% CI, 21.1-37.2).
In a multivariate model, women who had an EDSS score less than 6 and ARR less than 1 had a mean time of therapeutic lag on disability progression of 26.6 (95% CI, 18.2-34.9) weeks. While this was not substantially different from men with an EDSS score less than 6 and ARR less than 1 (mean, 31.0 weeks; 95% CI, 25.3-36.8), longer lag times were observed among women with an EDSS score of at least 6 and ARR less than 1 (mean, 54.3 weeks; 95% CI, 47.2-61.5).
Among the disease relapse cohort, longer therapeutic lag was associated with women (mean, 14.3 weeks; 95% CI, 12.7-15.9), patients with EDSS scores of at least 6 (mean, 16.9 weeks; 95% CI, 13.8-19.9), and ARR less than 2 (mean, 14.9 weeks; 95% CI, 13.4-16.4) compared with men (mean, 9.8 weeks; 95% CI, 7.2-12.4), patients with EDSS scores less than 2 (mean, 9.2 weeks; 95% CI, 7.0-11.4), or those with ARR of at least 2 (mean, 11.1 weeks; 95% CI, 9.3-12.8).
The results of this study may not be generalizable to patients who are within 3 years of their MS diagnosis or who have been treated for less than 1 year, as such patients were excluded from this analysis.
Study researchers concluded, “Our findings are relevant to reanalysis of clinical trials in patients with more advanced disease and design of clinical trials in progressive MS. Treatment outcomes in cohorts enriched with patients with higher disability scores and relapse activity should be interpreted with the expected duration of therapeutic lag in sight.”
Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Roos I, Leray E, Frascoli F, et al. Determinants of therapeutic lag in multiple sclerosis. Mult Scler. Published online January 11, 2021. doi:10.1177/1352458520981300