There might be years-long lags in response to disease-modifying drugs in patients with progressive forms of multiple sclerosis (MS), according to a study that analyzed data from two large clinical trials of progressive MS patients.
The study fuels the idea that clinical trials of disease-modifying drugs for progressive MS need to take into account that a treatment effect may take years to develop. Ultimately, however, more research is needed to confirm this idea, researchers said.
Maria Pia Sormani, PhD, from the University of Genova in Italy who presented the results in her talk titled “Therapeutic lag: Is treatment effect delayed in progressive MS?” at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress in London, Sept. 14-17.
The data were presented during a session titled “Insights to long term treatment effects from MS registries and databases,” and provides evidence for a theory among researchers that clinical trials in progressive MS fail since they are too short in time. Treatment response in progressive patients, some argue, may be delayed compared to that seen in relapsing forms of the disease.
Sormani and her colleague, Gavin Giovannoni, PhD, from Queen Mary University of London, analyzed data from two MS trials – the SPECTRIMS and PROMISE.
The SPECTRIMS extension study ran for six years and included 618 secondary progressive MS patients treated with two different doses of Rebif [interferon (IFN) beta-1a]. The PROMISE study looked at 943 primary progressive MS patients treated with Copaxone [glatiramer acetate (GA)] for three years. The later study was terminated early after an independent data safety monitoring board saw no significant treatment effect after three years.
Researchers analyzed the data from the two trials using a statistical method that could take into account a delay in treatment effect. The analysis suggested that such an effect was seen after 2.5 years in the SPECTRIMS study, and two years in the PROMISE trial.
When Sormani and Giovannoni compared the treatments after these cut-off points, it showed the therapies did have an effect — both lowered the risk of progression by 35%. The analysis also showed that the delay in treatment effect became larger as the level of disability grew.
“This post-hoc analysis run independently on data from two clinical trials testing the effect of two different drugs (IFN and GA) in two populations of progressive MS patients [secondary progressive and primary progressive] indicates that the effect of both drugs become evident after 2-2.5 years from treatment start. These observations support the hypothesis that in progressive MS it may take several years for DMTs [disease-modifying drugs] to manifest their effect on disease progression and warrant further confirmation on independent long term clinical data,” the researchers concluded in their ECTRIMS’s abstract.