In patients with relapsing-remitting multiple sclerosis (RRMS), fingolimod may protect against deep gray matter (dGM) and thalamus volume loss and may also lead to slower disability progression compared with placebo, according to an analysis published in Neurology.
The investigators analyzed pooled data from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis FREEDOMS and FREEDOMS II phase 3 trials, using data from the fingolimod program. In the pooled analysis, a total of 2064 participants with RRMS received 0.5 mg fingolimod (n=783), 1.25 mg fingolimod, or placebo (n=773). At 12 and 24 months, the investigators evaluated baseline changes in dGM and thalamic volumes. White matter and ventricular volume changes were also evaluated.
Participants receiving placebo experienced brain volume reductions mostly in the cortical GM, with relative changes from baseline being stronger in the dGM. During the full 24-month study period, both doses of fingolimod (1.25 mg and 0.5 mg) were associated with significant reductions in brain volume loss of 39.6% and 31.7%, respectively (P <.001). Additionally, 1.25 mg and 0.5 mg fingolimod doses were associated with reductions in dGM loss by 26.6% (P <.001) and 14.5% (P =.017), respectively.
Significant reductions in thalamus volume loss were also observed with fingolimod (49.7% [P <.001] and 26.1% [P =.006]). In addition, there was significantly less white matter loss and ventricular volume enlargement among those receiving fingolimod compared with placebo (all P <.001). Patients taking placebo who demonstrated a high dGM (hazard ratio 0.54; P =.0323) or thalamic (hazard ratio 0.58; P =.0663) volume at baseline were less likely to experience worsening of disability. Comparatively, participants who were treated with both doses of fingolimod experienced less overall progression of disability than those receiving placebo (P =.0457).
The investigators suggest a potential systematic bias in determining white matter and GM borders as well as the lesion-filling algorithm that was used in this study.
Considering that reduced thalamic and dGM volumes provide predictive value for future worsening of disability, the findings from this study support “the clinical relevance of therapeutic effects on dGM and thalamic volume loss for treatment decisions.”
Gaetano L, Häring DA, Radue EW, et al. Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis [published online April 10, 2018]. Neurology. doi: 10.1212/WNL.0000000000005292