New method confirms positive clinical trial results for MS drug Tecfidera
Study: It uses real-world data to extend findings to underrepresented patients
Written by |
Three people sit at a table looking at graphs and charts. (Photo by iStock)
- Target trial emulation (TTE) validated Tecfidera's effectiveness for relapsing-remitting multiple sclerosis (RRMS) using real-world data.
- TTE showed Tecfidera outperformed glatiramer acetate in RRMS patients, including older adults and those with severe disability.
- This method helps extend clinical trial findings to underrepresented patient groups, supporting more inclusive treatment decisions.
A new method called target trial emulation (TTE) used real-world data to successfully replicate the findings of a previous clinical trial of Tecfidera (dimethyl fumarate) involving people with relapsing-remitting multiple sclerosis (RRMS), according to a study report.
The approach also generated new evidence showing that Tecfidera outperformed glatiramer acetate (sold as Copaxone among others) in patient groups excluded from the original trial, including older adults, patients with more severe disability, or those who had not recently experienced a relapse.
“This study highlights how target trial emulations can bridge the gap between evidence from randomized controlled trials and from real-world patient data,” researchers wrote, adding that generating new evidence from underrepresented patients may support more inclusive care decisions.
The study, “A target trial emulation of the CONFIRM study with an extension to subgroups: an example for relapsing-remitting multiple sclerosis,” was published in the European Journal of Epidemiology.
Method mimics structure of proper clinical trial
MS most commonly affects adults between the ages of 20 and 50, and is diagnosed more often in women. The relapsing-remitting form of the disease — where symptoms flare up and then partially or fully recover — is the most common type.
Because of this, most clinical trials testing MS treatments have been built around this core demographic and tend to exclude older people and other groups of patients. As a result, doctors have limited evidence to guide care for these patients.
Running new clinical trials to fill these gaps is expensive, time-consuming, and often difficult to justify. An alternative is to study what happens to patients in the real world, outside of tightly controlled trial settings. However, this kind of research carries risks, including hidden biases that can lead to misleading conclusions.
To address this challenge, researchers have turned to a method called “target trial emulation” — a framework designed to make real-world studies more rigorous by closely mimicking the structure of a proper clinical trial.
A team in the Netherlands used this framework to reproduce the Phase 3 CONFIRM clinical trial (NCT00451451), which tested Tecfidera (now also available as generics) against glatiramer acetate or a placebo in more than 1,400 RRMS participants.
Study includes patients who would normally be left out
First, researchers used real-world data from the Swedish Multiple Sclerosis registry and replicated CONFIRM’s strict eligibility rules to mirror the trial as closely as possible. Then, they relaxed those rules to include patients who would normally be left out — particularly adults older than 55, patients with more severe disability, or those who had not recently relapsed.
The main outcomes were the average number of relapses per year and the likelihood of a first relapse over 96 weeks, or nearly two years.
“The first step in our two-step approach thereby provides an indication that the correct methodology was applied by replicating trial results, while in the second step, the added value of the observational data is embraced,” the researchers wrote.
When the team applied the TTE framework under strict, trial-like conditions, Tecfidera was associated with fewer relapses per year than glatiramer acetate (0.88 vs. 1.17), matching the original CONFIRM results. Under the more inclusive conditions, Tecfidera again outperformed glatiramer acetate (0.20 vs. 0.34).
When the two medications were directly compared, Tecfidera was associated with 25% fewer relapses than glatiramer acetate under strict conditions and 42% fewer relapses under a more inclusive real-world approach.
This study can be used as [a] guiding example for future observational studies that wish to incorporate the TTE framework, as well as embrace the wider variety in the patient population often ignored in experimental settings.
Researchers then assessed the likelihood that a patient would experience their first relapse during the study period. Under the strict conditions, patients on either medication had a similar chance of experiencing a first relapse, consistent with findings from the original CONFIRM trial.
Meanwhile, in the broader real-world scenario, Tecfidera-treated patients were nearly half as likely to experience a first relapse compared with those on glatiramer acetate.
Notably, the results were most consistent with the original trial when the analysis focused only on patients who had experienced a relapse in the year before the study. When relapse-free patients were included, comparisons with the trial were less consistent.
“This study can be used as [a] guiding example for future observational studies that wish to incorporate the TTE framework, as well as embrace the wider variety in the patient population often ignored in experimental settings,” the team wrote.
Leave a comment
Fill in the required fields to post. Your email address will not be published.