Abstract: MRI Outcomes and MS Diagnosis Criteria in the Combirx Trial (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Friday, May 31, 2013: 4:15 PM

Flavia Nelson, MD , The University of Texas Health Science Center at Houston, Houston, TX

Amber Salter, MPH , Biostatistics, University of Alabama at Birmingham, Birmingham, AL

Ponnada Narayana, PhD, MSc , The University of Texas Health Science Center at Houston, Houston, TX

Tarah Gustafson, BSN , Neurology, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY

Robin Conwit, MD , NINDS, NIH, Bethesda, MD

Jing Wang, MS , Biostatistics, University of Alabama at Birmingham, Birmingham, AL

Stacey S Cofield, PhD , Biostatistics, University of Alabama at Birmingham, Birmingham, AL

Gary Cutter, PhD , Biostatistics, University of Alabama at Birmingham, Birmingham, AL

Fred D. Lublin, MD , Neurology, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY

Jerry Wolinsky, MD , The University of Texas Health Science Center at Houston, Houston, TX

Background: CombiRx was a double blind, multi-center randomized clinical trial of 1008 persons with relapsing remitting MS, comparing 50% of participants on interferon beta 1a and glatiramer acetate versus 25% on each of the single agent arms with matching placebo. Entry criteria included: EDSS ≤ 5.5, RRMS diagnosis by Poser (PS) or 2001 McDonald (MC) criteria, 18-60 years of age, at least 2 relapses in prior 3 years, no prior use of either medication; and were followed up to 7 years with clinical and MRI measures.

Objectives: To describe and compare MRI metrics for participants diagnosed using PS or MC criteria, including Gd number, T2 lesion volume, total lesion volume (TLV), normalized CSF (nCSF) and combined unique activity.

Methods: MRI with Gd was obtained at baseline, months 6, 12, 24, 36, 48, 60 and at study exit. Covariate adjusted repeated measures mixed models with heterogeneous variance by diagnosis criteria, were used for comparison of MRI metrics overtime. Covariates included baseline group differences and MRI metric at baseline.

Results: Of the 1008, 784 (77.8%) were diagnosed by PS with 2 or more clinical attacks (CA) with 2 objective clinical lesion (CL), and 224 (22.2%) by MC, not different across treatment groups (p=0.44). Of the 224 MC: 41.5% had 2 or more CA with 1 objective CL, 36.6% had 1 CA with 2 or more CL, and 21.9% had 1 CA with 1 CL. PS were older (38.3 vs 35.8, p=0.0007), experienced more relapses in the prior 3 years (2.5 vs 2.2, p<0.0001), and had a longer duration of symptoms (median 2 vs. 1 year, p<0.0001). At entry MC had lower values for all MRI metrics, with statistical differences for number and volume of T1 and T2 lesions, TLV, and nCSF a measure of atrophy. By month 6 those diagnosed by MC criteria had similar MRI measures to PS participants for all metrics except nCSF. MC participants had lower atrophy measures compared to PS through year 2 (MC lower than PS by: Month 6, 0.005, p=0.0053; Yr 1, 0.006, p=0.0029; Yr 2, 0.005, p=0.0175) but are similar by year 3 through the end of the trial.

Conclusions: At study start participants diagnosed according to the 2001 McDonald criteria exhibit lower MRI activity compared to Poser diagnosis but after treatment initiation MRI measures are similar for the duration of the trial, with the exception of atrophy measures. Although McDonald criteria allow for earlier diagnosis of MS these participants appear to have similar on trial MRI activity to those diagnosed by Poser criteria.

3.2 MRI Outcomes and MS Diagnosis Criteria in the Combirx Trial