Tissue Damage protection with fingolimod

Wolinsky et al. Brain Volume as a Predictor of Disability in Primary Progressive Multiple Sclerosis: Evidence from the INFORMS Trial. Neurology , 2016 vol. 86 no. 16 Supplement S51.007

OBJECTIVE: To determine the role of brain volume (BV) as a predictor of disability worsening in primary progressive multiple sclerosis (PPMS). BACKGROUND:Normalized BV (NBV) and on-study BV loss (BVL) are predictive of disability worsening in relapsing MS (RMS). The role of BV in PPMS is unclear. METHODS:We repeated RMS analyses in PPMS data using INFORMS (≥3 years study of fingolimod 0.5mg [N=336] vs placebo [N=487]). INFORMS placebo-treated patients (natural history) were grouped into “low NBV” (n=70), “medium NBV” (n=351) and “high NBV” (n=61) categories using multiple regression to adjust (and test) for baseline characteristics: T2 volume, EDSS, MS duration, age and gender. NBV category was tested as a predictor of disability worsening according to the INFORMS primary efficacy composite endpoint, using Kaplan-Meier (KM) estimates at Year 3, Cox regression and log-rank test. On-study BVL was described by treatment for baseline T2 volume and Gd-T1 counts categories, as previously used in RMS. RESULTS:PPMS patients with baseline high NBV were at lowest risk (KM: 67[percnt]) of disability worsening, followed by medium (74[percnt]) and low NBV (91[percnt]), corresponding to a 35[percnt] risk reduction for high vs. low NBV (Cox’s model hazard ratio: 0.65, p=0.0507; Log-rank test: p=0.0297). Low NBV at baseline was best correlated with high baseline T2 volume and older age (both p<0.0001). BVL over 3 years was best predicted by baseline T2 lesion volume (p<0.0001). A minority of INFORMS patients with BVL measures had baseline Gd+ lesions (n=107/820, 13.0[percnt]); in those patients, BVL was more pronounced and a significant fingolimod effect on BVL was visible. CONCLUSIONS:Low NBV predicted disability worsening in PPMS, similar to RMS. A history of MRI activity (high baseline T2 volume) was the best predictor of on-study BVL. Patients with acute inflammation (baseline Gd+ lesions) experienced greater BVL, which was reduced by fingolimod. 

If your brain doesn't shrink when you are fingo you have a lowerchance of disability worsening. Alot of shrinking and the chances of worsening is higher which is not surprising as it means nerves are being lost. This shrinkage is associated with MRI lesions. So relapses (lesions) are bad for you, so try to stop them.

De Stefano N, Tomic D, Radue EW, Sprenger T, Meier DP, Häring D, Sormani MP. Effect of fingolimod on diffuse brain tissue damage in relapsing-remitting multiple sclerosis patients.Mult Scler Relat Disord. 2016 May;7:98-101.

BACKGROUND:Multiple sclerosis (MS) affects all areas of the brain resulting in both focal and diffuse damage. In Phase 3 clinical trials, fingolimod showed significant reductions in both focal lesions and rate of brain volume loss (BVL) in patients with relapsing-remitting MS.
OBJECTIVE:To investigate if the effects of fingolimod 0.5mg on BVL are mediated exclusively through its effects on focal damage or if fingolimod also acts independently in reducing diffuse damage.
METHODS:This was a pooled post-hoc analysis of patients from two Phase 3 studies (FREEDOMS [N=1272] and FREEDOMS II [N=1083]), with no evidence of focal disease activity as defined by absence of gadolinium-enhancing lesions at baseline and new active lesions and clinical relapses at follow-up. The percent brain volume change (PBVC), as a measure of diffuse tissue damage, was assessed at Month (M) 12 and M24 by using the Structural Image Evaluation using Normalization of Atrophy (SIENA) method.

RESULTS:Of 1088 patients, 638 (PBO, n=127; fingolimod, n=511) at M12 and 450 patients (PBO, n=68; fingolimod, n=382) at M24 showed no focal activity. Fingolimod significantly reduced PBVC by 65.5% over 12M (fingolimod vs. PBO: -0.16 vs. -0.45; p=0.001) and by 48.2% over 24M (-0.42 vs. -0.81; p=0.004). An absolute difference in PBVC of -0.27% (p<0.001) in favor of fingolimod vs. PBO over 24M was evident. 54% (-0.27%/-0.51%) of effects of fingolimod on PBVC are independent of its effects on visible focal damage.
CONCLUSIONS:The effect of fingolimod on diffuse damage is partly independent of its treatment effect on focal damage, suggesting that both inflammatory and neurodegenerative components of MS are affected.

So we all already know that fingo can slow the rate of loss of brain tissue as you would expect with any agent that can truely stop inflammation but in the paper it suggests there is more. 

Does it really affect neurodegeneration? If it did why did it fail to affect PPMS...case rests me lord.