Abstract: Clinical 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)

Saturday, June 1, 2013

Khurram Bashir, MD, MPH , Neurology, The 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

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

Tarah Gustafson, BSN , Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

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

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

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

Fred D. Lublin, MD , Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York, NY

Background: The CombiRx trial is a double blind, multi-center randomized clinical trial studying 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. Subject entry criteria include: EDSS ≤ 5.5, RRMS diagnosed by Poser or McDonald criteria, 18-60 years of age, at least 2 relapses in prior 3 years, and no prior use of either medication. Participants were followed for up to 7 years with both clinical and MRI measures.

Objectives: To compare clinical course for participants diagnosed using Poser (PS) or 2001 McDonald (MC) criteria, including pre- and on-study relapse activity, EDSS changes and confirmed disability.

Methods: Relapse types included: protocol defined and non-protocol defined exacerbations (PDE, NPDE). PDE required: new/worsening symptoms ≥ 24hours, no fever, change in EDSS/FS, examined ≤ 7 days; NPDE: same as PDE but examined > 7days. ARR and Cox proportional hazards (CPH) regression were used to assess relapse types by diagnosis criteria. Changes in EDSS over time were assessed using a repeated measures mixed model, comparison of the proportion of participants with progression using Logistic regression. All models were adjusted for baseline differences.

Results: Of the 1008 randomized, 77.8% (784) were diagnosed by Poser; 22.2% (224) by McDonald. PS were older (38.3 vs 35.8, p=0.0008), 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 yrs, p<0.0001) compared to MC participants. The proportion randomized to each treatment arm was not different (p=0.44). Average years on study (SD): 3.9(1.7), did not differ by diagnosis group (p=0.85). Over the 7 years: 395 PDE and 415 NPDE were confirmed with 3881.6 total person years on study. ARR by diagnosis for PDE: 0.07 MC, 0.11 PS; with HR of 0.53 for MC vs PS (p<0.0001); for PDE+NPDE: 0.15 MC, 0.22 PS; with HR of 0.65 for MC vs PS (p<0.0001).

Conclusions: Participants diagnosed by 2001 McDonald criteria are at a lower risk of on-study relapse compared to those diagnosed by Poser criteria over the duration of the CombiRx trial, though ARR for both groups are low. EDSS changes and confirmed disability will also be presented.

P42 Clinical Outcomes and MS Diagnosis Criteria in the Combirx Trial