Natalizumab or Fingolimod After First-Line Drugs in MS?

October 11, 2018

BERLIN — When switching patients with multiple sclerosis from first-line treatments after a relapse, natalizumab (Tysabri, Biogen) appears to show a greater benefit compared with fingolimod (Gilenya, Novartis), especially for those patients with more active disease, a new study indicates.

"This propensity score–matched analysis suggests that patients who relapse while on first-line therapies have significant reductions in annual relapse rate and increases in confirmed disability improvement when switching to natalizumab versus fingolimod," reported lead author Tim Spelman, MBBS, Monash University, Melbourne, Australia. "Patients with more active disease (>1 relapse on first-line drugs) had the most benefit on natalizumab vs fingolimod."

"There isn't much clinical data to support a clinician's decision making when a patient fails on first line drugs," he told Medscape Medical News. "A common choice may be natalizumab or fingolimod. Many may choose fingolimod for convenience or because of concerns about PML [progressive multifocal leukoencephalopathy] on natalizumab. But these data support use of natalizumab in those patients with more disease activity."

Spelman concluded: "When we have a large enough dataset, we can demonstrate what clinicians have suspected all along — that the drugs available for MS treatment do vary, and it is important to consider the level of activity. All this points to more tailored treatment at the end of the day. If we can identify patients most likely to respond to treatment, we can make sure the right patients receive the right therapies."

The study was presented here at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018.

Commenting on the study for Medscape Medical News, chair of the ECTRIMS session at which it was presented, Olaf Stuve, MD, University of Texas Southwestern Medical Center, Dallas, said: "I think this study confirms what we have seen in some other phase 4 studies, that natalizumab might be slightly more potent than fingolimod as a sequential follow-up therapy in MS patients who have failed another disease-modifying drug."

But, he added: "Considering the side effect profile of each drug, natalizumab is not the right therapy for everybody. Risk stratification for PML includes JC virus seropositivity, so because of this many clinicians would still opt to use fingolimod as the drug to switch to despite these data — simply to avoid the risk of PML.

"Yes, these data suggest natalizumab may be better for patients with more aggressive disease — those with most relapses — and yes, I would probably choose natalizumab over fingolimod for these patients unless there are comorbidities that excludes them," Stuve said. "However, in terms of practicality, many neurologists don't look at their patients with this amount of detail — they may not look at how many relapses patients would have had in preceding years."

In his presentation, Spelman noted that analyses of comparative effectiveness using real-world evidence are increasingly being considered by regulatory bodies in their decision making. And although several comparative effectiveness studies have been conducted in observational settings on switching to fingolimod or natalizumab after first-line drugs fail, results have conflicted, and the patients in the studies were not stratified on the basis of disease activity before the drugs were switched.

For the current study, the researchers investigated at this issue in a large cohort of patients included in the MSBase Registry using propensity scoring to reduce bias and stratifying patients by disease activity.

In the study, 1:1 propensity score matching was used to match patients who were switched to natalizumab or fingolimod on the basis of many variables, including age, sex, disease duration, treatment history, EDSS score, and number of switches in the past 1 and 2 years. A total of 1000 patients on each switched treatment were included in the analysis.

Results showed that in the whole population, the annualized relapse rate (the primary endpoint) was reduced by 34% in patients switched to natalizumab versus those switched to fingolimod.

Table 1. Annualized Relapse Rate in Patients Switched to Natalizumab or Fingolimod

Endpoint Natalizumab (n = 1000) Fingolimod (n = 1000) Relative Risk (95% CI) P Value
Annualized relapse rate 0.189 0.285 0.66 (0.59 - 0.74) <.001

 

There was no difference in confirmed disability progression with the two drugs, but more of the patients who were switched to natalizumab showed improvement in disability.

Table 2. Percentage of Patients Showing Disability Progression and Disability Improvement

Endpoint Natalizumab (n = 1000) Fingolimod (n = 1000) Relative Risk (95% CI) P Value
24-week confirmed disability progression (% of patients) 15.9 12.0 1.14 (0.88 - 1.47) .339
24-week confirmed disability improvement (% of patients) 24.3 18.4 1.27 (1.03 - 1.57) .024

 

The greatest benefit of switching to natalizumab vs fingolimod was seen in patients with the most active disease (two or more relapses within 12 months before switching).

Table 3. Annualized Relapse Rate in Patients Switched to Natalizumab or Fingolimod, Stratified by Disease Activity Before Switching

Endpoint Natalizumab (n = 1000) Fingolimod (n = 1000) Relative Risk (95% CI) P Value
≥2 relapses within 12 months 0.230 0.360 0.64 (0.55 - 0.74) <.001
1 relapse within 12 months 0.166 0.234 0.71 (0.60 - 0.84) <.001

 

Table 4. Percentage of Patients With Confirmed Disability Improvement When Switched to Natalizumab or Fingolimod, Stratified by Disease Activity Before Switching

Endpoint Natalizumab (n = 1000) Fingolimod (n = 1000) Relative Risk (95% CI) P Value
≥2 relapses within 12 months 24.5 18.6 1.42 (1.04 - 1.94) .027
1 relapse within 12 months 22.1 20.5 1.15 (0.85 - 1.56) .365

 

"This study illustrates that real-world registry data are a viable option for filling in gaps for decision making at regulatory level," Spelman added. "These types of studies are now being requested by regulators themselves — that signals an acceptance of the quality of the data and the methods we used to attempt to isolate treatment effects."

Dr Spelman has disclosed no relevant financial relationships.

34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018. Abstract 59, presented October 10, 2018.

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