Brain Volume as a Predictor of Disability in Primary Progressive Multiple Sclerosis: Evidence from the INFORMS Trial (S51.007)

To determine the role of brain volume (BV) as a predictor of disability worsening in primary progressive multiple sclerosis (PPMS)  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.  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.  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, ] in those patients, BVL was more pronounced and a significant fingolimod effect on BVL was visible.  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. Study supported by Novartis Pharma AG. Disclosure: Dr. Wolinsky has received royalty payments from Chemicon International through the University of Texas Health Science Center at Houston. Dr. Haering has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Sormani has received personal compensation for activities with Novartis, Roche, Genzyme, Merck Serono, TEVA, Synthon, and Biogen Idec as a consultant and speaker. Dr. Lublin has received personal compensation for activities with Acorda Therapeutics, Inc. Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc.,Genzyme, Sanofi, Celgene, Cognition Pharmaceuticals, Inc. Elsevier, NIH, and NMSS. Dr. Miller has nothing to disclose. Dr. Freedman has received research support from Bayer Healthcare and Genzyme. Dr. Cree has received personal compensation for activities with Abbvie, Biogen Idec, EMD Serono, Genzyme/sanofi aventis, Medimmune, Novartis and Teva. Dr. Cree has received research support from Acorda, EMD Serono, Hoffman La Roche, MedImmune, Novartis a Dr. Weiner has nothing to disclose. Dr. Lubetzki has received personal compensation for activities with BiogenIdec, Novartis, Genzyme, and Roche. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck Co. Inc. NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Pharmaceuticals, Genzyme, and Roche. Dr. Merschhemke has received personal compensation for activities with Novartis as an employee. Dr. Li has received personal compensation for activities with Novartis Pharmaceuticals as an employee. Dr. Putzki has received personal compensation for activities with Novartis Pharma AG. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH.