Associate Professor Tomas Kalincik
Continued treatment with disease-modifying therapies (DMTs) significantly reduces relapses and disability accrual in the long term for patients with relapsing-remitting MS.
A study using data from 14, 717 patients in the international MSBase Neuroimmunology Registry found relapses reduced by about 40% (HR 0.60; p = 0.0016) in a “pseudo cohort” of patients continuously treated with DMTs.
Similarly, treatment significantly reduced any worsening of disability (HR 0.56; p= 0.0026) and progress to confirmed EDSS step 6 (HR 0.33; p = 0.00019) compared to a pseudo cohort of untreated patients.
The sophisticated analysis uses observed data and simulates what would have happened if patients were exposed to treatment for the whole duration of follow-up (15 years) or not.
The counterfactual framework helps adjust for factors such as real world breaks from treatment due to issues such as pregnancy, concern about side effects, or concomitant disease.
“The study design enables an analyst to quantify the probability of reaching disease outcomes under hypothetical conditions when the observed cohorts would remain always treated vs. never treated for the full duration of the study period,” the study said.
Long term impact
Lead investigator Associate Professor Tomas Kalincik told the limbic that clinical trials have shown that all of the DMTs reduce the frequency of relapse over 2 or 3 years – the standard duration of a RCT.
“Now a question that is often asked and very difficult to answer is what is the long term impact of these treatments. And that is much more difficult to do because in a clinical trial, it is neither ethical nor financially feasible to keep people randomised and blinded to treatments for 15 years or more.”
Associate Professor Kalincik, head of the Clinical Outcomes Research (CORe) Unit at the University of Melbourne, said the investigators were very pleased to see the results were better than those from clinical trials.
“Here people cycle through the various therapies based on conversations with their neurologists. They always aim for the best treatment for them at a given time point in their lives.”
“So it is logical that we are seeing better outcomes than in trials because the patients and doctors are working together to maximise the impact of treatment, unlike in clinical trials where things are set in stone – preserving randomisation to test the true effect of the treatment only.”
“In a sense what we are looking at is the effect of optimised life-long treatment.”
He said the findings would be reassuring for clinicians, patients and regulators.
“It is important information for patients and the community especially if people are hesitant about being on treatment – is it worth it versus potential side effects?”
“There’s a strong message here that it is absolutely worth it and for being consistent about staying on treatment.”
“And it’s important for regulators who ask if it is worth paying for these patients to stay on treatment. Yes, it is absolutely worth it. We are keeping these patients healthier and consequently, they are capable of being active contributors to society, including staying in the workforce.”
He said treatment could also lead to disability improvement but was mostly restricted to the initial five years after the onset of disease.
“Therefore, sustained, long-term immunotherapy from early stages of MS is advisable as a strategy to preserve patients’ neurological capacity over the long-term,” the study concluded.
The study was published in Neurology.
Disclosures: The operation of MSBase Registry is funded by a number of drug companies. However this analysis, driven by CORe at the University of Melbourne, was funded by the NHMRC.