DX52
Efficacy Outcomes in Patients Randomized to Fingolimod or Injectable Disease-Modifying Therapies in PREFERMS: Effect of Previous Treatment Cycles

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Samuel F Hunter, MD, PhD , Advanced Neurosciences Institute, Franklin, TN
Florian P Thomas, MD, PhD, MA , Seton Hall-Hackensack Meridian School of Medicine, South Orange, NJ
Xiangyi Meng, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Lesley Schofield, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Scott Kolodny, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Nadia Tenenbaum, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Bruce AC Cree, MD, PhD , UCSF Neurology, Weill Institute for Neurosciences, San Francisco, CA
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Background:

PREFERMS was a 12-month, phase 4, active-controlled, open-label, multicenter study that compared treatment retention and clinical outcomes with fingolimod and injectable disease-modifying therapies (iDMTs) in patients with relapsing multiple sclerosis. Patients were randomized (1:1) to fingolimod 0.5 mg/day or a pre-selected iDMT; one treatment switch was allowed for any reason after 3 months, or before for efficacy or safety reasons.

Objectives:

To assess the impact of the number of previous cycles of iDMT (two, one or none) on response to fingolimod in PREFERMS.

Methods:

At enrollment, patients were treatment-naïve (n=404, 46.2%) or had previously received one class of iDMT (interferon or glatiramer acetate; n=471, 53.8%). Of these patients, three sets were analyzed post hoc for hypothesis generation only, according to their iDMT treatment history. Group A: patients previously treated with an iDMT, randomized to a new iDMT, and who later switched to fingolimod (n=155). Data from Group A are reported at two stages, at the last study visit before switching to fingolimod (after 2 iDMT cycles, pre-fingolimod; Group A1), and at the end of study after these patients had switched to fingolimod (after 2 iDMT cycles, post-fingolimod; Group A2). Group B: patients previously treated with an iDMT, randomized to fingolimod (after 1 iDMT cycle, post-fingolimod, n=233). Group C: treatment naïve patients who were randomized to fingolimod (no iDMT cycles, post-fingolimod, n=213). Data from Groups B and C are reported from the last study visit at which patients received fingolimod. The following outcomes were analyzed for all groups: mean exposure-adjusted percentage brain volume loss from baseline (BVL), mean number of new gadolinium-enhancing (Gd+) lesions and the mean change in Gd+ lesion count from baseline.

Results:

In Group A1, BVL was –0.902%. BVL from baseline was numerically smaller in all groups after fingolimod (Group A2, –0.416%; Group B, –0.365%; Group C, –0.606%). The number of new Gd+ lesions in group A1 was 1.462, numerically higher than for all groups after fingolimod initiation (Group A2, 0.542; Group B, 0.131; Group C, 0.189). The change in Gd+ lesion count showed no reduction in Group A1 (0.039), but decreased with fingolimod in Groups A2 (–0.493), B (–0.386) and C (–1.378).

Conclusions:

After fingolimod initiation, outcomes improved in patients with two previous iDMTs. The data suggest that improvements may be seen with fingolimod irrespective of the number of iDMTs previously received.