AT ACTRIMS FORUM 2016
NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Research from Australia shows that disability in multiple sclerosis (MS) is independent of past damage, even in people whose disease is moderately advanced, with further disease progression varying widely in severity.
The findings should prompt a rethink of the policy of ceasing treatment when MS-related disability becomes more advanced.
“Our main findings were that moderately advanced multiple sclerosis is indeed independent of previous disease, but still extremely variable. Higher relapse rates later in disease increased the risk of disability worsening. More promisingly, more time spent on therapy later in disease lowered the risk of disability progression to EDSS [Expanded Disability Status Scale] 6 or 6.5,” Nathaniel Lizak said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The study sought to identify factors that modified progression in early and moderately advanced MS. Three prior cohort studies had not shed light on the variability in disease trajectory during moderately advanced MS.
“We wanted to examine how much variability there was later in disease, what determined this variability, and to confirm whether later disease was really independent of previous disease, as was suggested in previous studies,” said Mr. Lizak of Monash University, Clayton, Australia, and the University of Melbourne. The influences of relapse rate and proportion of time treated prior to and during each disability time period, age, and disease duration at baseline on the progression to moderate MS disability (EDSS 6 or 6.5) were assessed. The hypothesis was that, even at a later stage of MS, disease progression varies from patient to patient, and that some patients can benefit from immunomodulatory therapy.
The time between EDSS steps 3-6 (n = 1,560, 71% female, 40.9±9.9 years old at baseline), 4-6 (n = 1,504, 69% female, 43.0±9.6 years old at baseline), and 6-6.5 (n = 1,231, 67% female, 46.5±10.2 years old at baseline) were analyzed for the 32,336 patients included in the MSBase large, international, observational MS cohort study who met the inclusion criteria. Median disease duration at baseline was 9.4, 11.1, and 14.0 years in the same respective order.
Pre- and postbaseline disability trajectories showed large coefficients of variance and did not correlate. The probability of reaching the outcome EDSS was independent of prebaseline variables, but was increased if relapse during any particular EDSS was more frequent (hazard ratios, 1.58-3.07; P less than .001). At each measured stage of MS, higher-efficacy therapies were beneficial and lowered the risk of progression (HR, 0.27-0.68; P less than .02).
Some countries, such as New Zealand, by policy don’t allow patients to receive treatments if they display moderate or significant disability. In other places this can be common practice because of concerns with treatment-related side effects or affordability. The main driver of this practice is that the clinical trials of most MS therapies that have validated these medications specifically recruited patients with low disability scores. So, according to Mr. Lizak, the evidence exists only for therapies at lower disability scores.
“These results are important as they show that there is still hope. Reaching disability landmarks of EDSS 3, 4, and 6 does not guarantee continuous worsening of disability. Doctors still have the ability to reduce their patients’ risk of attaining further disability, even at later stages of disease,” said Mr. Lizak.
The hope is that the data will change clinical practice to encourage more therapy even when substantial disability has accumulated.
“Translating results into everyday practice is difficult, and doctors must always weigh the risks and benefits. We hope that our work will influence the clinical decision to, where in doubt, favor high-efficacy treatments at later disease stages. That’s not to say that patients should be blindly treated, as side effects always merit consideration. But we hope our work will inform neurologists that there is evidence supporting treating patients with more advanced disability. Where, by practice or policy, treatments are not provided to patients who have accumulated significant disability, we hope to change such clinical practice,” said Mr. Lizak.
The study did not require funding. Mr. Lizak had no disclosures.
