Table 1.

Summaries of Pivotal Trials of Interferons in RRMS

Trial	Primary Outcome	Secondary Outcome	Intervention	Significant Results	Adverse Events
IFNB MS Study Group,2 1993 (2 years)	● Differences in ARR● Proportion of patients exacerbation-free	● Time to exacerbation● MRI lesion load● Severity of exacerbations● Change in EDSS	1.6MIU IFNB 1b or 8.0 MIU IFNB-1b SC every other day vs placebo	● ARR lower in both treatment groups (placebo: 1.27; 1.6MIU 1.17; 8.0MIU 0.84)● More patients in 8.0MIU group exacerbation-free (did not remain significant at 3 years)● Prolongation of time to first and second exacerbations in 8.0MIU group● Benefit in MRI lesion burden (placebo with 20% increase, 1.6MIU with 10.5% increase, 8.0MIU with 0.1% decrease)● Less moderate and severe exacerbations in 8MIU group● No significant change in EDSS in any group	● Mild, intermittent lymphopenia, neutropenia anemia, thrombocytopenia● Abnormal liver enzymes● Injection site pain● Flu-like illness● Muscle aches● Fever● Chills● Neutralizing antibodies: 11% in placebo, 47% in 1.6MIU, 45% in 8.0MIU
MSCRG,8 1996 (2 years)	● Time to sustained disability progression	● Exacerbations● MRI	6.0 MIU IFNB-1a IM weekly vs placebo	● Delay in time to sustained EDSS progression (34.9% in placebo vs 21.9% with progression at 104 weeks)● Decreased number of exacerbations and annual relapse rates (0.90 in placebo and 0.61 in IFN)● Decreased number and volume gadolinium enhancement	● Mild anemia● Flu-like illness● Muscle aches● Chills● Fever● Asthenia● Neutralizing antibodies: 4% in placebo, 22% in IFN
PRISMS,9 1998 (2 years)	● Annualized relapse rate	● Times to first and second relapse● Proportion of relapse-free patients● Progression in disability● MRI activity	IFNB-1a 22µg or 44 µg SC three times weekly vs placebo	● Decreased relapse rates in both treatment groups (2.56 in placebo, 1.82 in 22µg and 1.73 in 44 µg)● Median time to first relapse delayed by 3 and 5 months in 22µg and 44µg, respectively● Longer time to sustained progression● Decreased T2 and gadolinium-enhancing lesions in both treatment groups	● Leukopenia● Elevated liver enzymes● Depression● Injection-site reactions● Flu-like illness● Neutralizing antibodies: 23.8% in 22µg and 12.5% in 44µg
ADVANCE,10 2014 (48 weeks)	● Annualized relapse rates	● Number of new or enlarging T2 lesions● Proportion of patients who relapsed● Proportion of patients with disability progression	Peginterferon beta-1a 125µg every 2 weeks or every 4 weeks, vs placebo	● Decreased annualized relapse rates (0.397 in placebo, 0.256 in every 2-week group, 0.288 in every 4-week group)● Decreased proportion of patients who relapsed (0.291 in placebo, 0.187 in every 2-week group, and 0.222 in every 4-week group)● Decreased sustained disability (0.105 in placebo and 0.068 in both treatment groups)● Decreased number and volume of T2 lesions	● Injection site reactions● Flu-like illness● Fever● Headache●