by Lindsey Shapiro, PhD | September 7, 2022
‘Small’ difference in disability worsening at 2 years seen across 5 trials
Off-label use of high-efficacy disease modifying therapies (DMTs) for people with progressive forms of multiple sclerosis (MS) appear to be as effective as on-label, or approved, DMTs for this MS patient group, a review study from Brazil suggests.
The meta-analysis, which included data from controlled clinical trials, found that rates of disability worsening after two years were similar among patients using on- or off-label treatments when compared with those given a placebo.
“The use of these off-label drugs may be a cost-reducing strategy to improve access to immunotherapy,” the researchers wrote, noting that the two DMTs approved for progressive MS are often not available to patients in low- and medium-income countries.
The study, “Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis,” was published in Acta Neurologica Scandinavica.
Progressive forms of MS — primary progressive MS (PPMS) and secondary progressive MS (SPMS) — are characterized by continuous symptom worsening and have proven more difficult to treat.
Many high-efficacy DMTs that have emerged in recent years are designed to treat relapsing MS types. Only two high-efficacy DMTs are approved for progressive forms of MS: Mayzent (siponimod) and Ocrevus (ocrelizumab).
Access can be an issue for 2 approved progressive MS DMTs
Novartis’ Mayzent is approved in the U.S., Europe, Canada, Australia, and several other countries for adults with active SPMS, characterized by the presence of relapses or brain lesions with active inflammation. Genentech’s Ocrevus is the only DMT for PPMS, approved in the U.S., Europe, and various other countries.
Still, “in clinical practice, access to these drugs for patients with primary progressive and secondary progressive MS is difficult,” the researchers wrote. “Furthermore, in some countries, being labeled as having progressive MS requires the cessation of DMDs use.”
Off-label use of other high-efficacy DMTs may offer a way of lowering treatment costs and increasing access for these patients, but the effectiveness of such treatments — relative to on-label options — has not been directly evaluated in appropriately controlled clinical trials.
Researchers at the University of São Paulo retrospectively analyzed published studies up to December 2021 reporting results of controlled trials comparing a high-efficacy DMT against a placebo in people with a form of progressive MS.
The final meta-analysis included five studies, each testing one of five high-efficacy DMTs: on-label Mayzent or Ocrevus, and off-label rituximab, Gilenya (fingolimod), or Tysabri (natalizumab). Gilenya and Tysabri are approved to treat active SPMS in the U.S., but not in Europe and other countries, including Brazil.
While each of the five DMTs have distinct modes of administration and mechanisms of action, all work, one way or another, by modulating the immune system. This is expected to suppress the abnormal immune responses that drive inflammation and neurodegeneration in MS.