Background: Currently approved disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) include two different interferon beta-1a (IFNB-1a) preparations: subcutaneous IFNB-1a (Rebif) 44 microg three times weekly and intramuscular IFNB-1a (Avonex) 30 microg once weekly.

Objective: This evaluation is of the Prospective and Retrospective Long-Term Observational Study of Avonex and Rebif (PROOF), which intended to compare relative efficacy and tolerability of the two INFB-1a products.

Methods: PROOF was analyzed in light of previous head-to-head studies comparing high- and low-frequency IFNB therapies.

Conclusions: Several limitations, including a retrospective-prospective design, retrospective assessment of variables without predefined criteria, limited prospective evaluation, and inadequate sample size, necessitate careful interpretation of their Results. Ultimately, the question of long-term efficacy of high- versus low-frequency INFB therapies remains unanswered.