OBJECTIVES: To compare baseline disease severity levels and ARRs across Class 1 DMD studies for multiple sclerosis. Clinicians and payers tend to compare the results of individual clinical trials utilizing relative risk reduction (RRR) for each disease modifying drug (DMD); however, inter-study variability, heterogeneity of the patient population, different baseline characteristics, and inconsistent placebo behaviors from different clinical trials makes comparison based on RRR inappropriate. Measurement of absolute risk reduction (ARR) may be a more appropriate assessment of benefit. METHODS: Class 1 studies of various DMDs were reviewed and analyzed to compare baseline Expanded Disability Status Scale (EDSS) scores and relapse rates across DMD study populations. The clinical benefit of DMDs versus placebo for 2-year relapse rates and proportion of progression-free patients was compared across all studies using ARR and number needed to treat (NNT). RESULTS: The proportion of patients with >2 relapses at baseline for subcutaneous (sc) interferon-beta (IFNB)-1a treated patients was higher than for natalizumab-treated patients (no data reported intramuscular (im) IFNB-1a, IFNB-1b, and glatiramer acetate (GA)). The proportion of patients with baseline EDSS scores of >=3 was greater among IFNB-1a sc-treated patients compared with IFNB-1a im and Natalizumab (no data reported IFNB-1b or GA). The ARRs for annualized relapse rates were 0.15, 0.24, 0.40, 0.41, and 0.45 for IFNB-1a im, GA, IFNB-1b, IFNB-1a sc, and natalizumab respectively (NNTs: 6.7, 4.2, 2.5, 2.4, 2.2). ARRs for progression-free patients were 0.13, 0.03, 0.08, 0.12, and 0.12 for IFNB-1a im, GA, IFNB-1b, IFNB-1a sc, and natalizumab respectively (NNTs: 7.7], 33.3, 12.5, 8.7, 8.7). CONCLUSION: Given the difference in baseline risk and severity levels across studies, ARR is the appropriate way to compare DMDs in the absence of head-to-head clinical trials. Results based on ARR showed that IFNB-1a sc has comparable therapeutic effect on efficacy measures when compared to natalizumab.