Interferon beta-1b was initially tested in a multicenter US trial involving 372 patients with RRMS and mild to moderate disability (EDSS up to 5.5). Treatment consisted of either 8 MIU (250 mcg) or 1.6 MIU (50 mcg) of IFN beta-1b or placebo given by subcutaneous injection every other day. The primary outcome was the relapse rate. Compared with placebo, treatment with the higher dose reduced the relapse rate by 31 percent, increased the time to first relapse and the proportion of patients who were relapse-free, and reduced by about 50 percent the number of patients who had moderate and severe relapses. There was, however, no difference in changes in EDSS scores between treatment groups. The patients in the placebo group had a mean increase of 17 percent in the total lesion load on brain MRI at three years compared with a mean decrease of six percent in those receiving high-dose IFN beta-1b. In addition, there was a significant reduction in disease activity as measured by the analysis of new or enlarging lesions on serial MRIs.

A second multicentre trial of IFN beta-1b was performed in Europe, including 718 patients with SPMS (EDSS at inclusion 3.0–6.5) whose disease had been clinically active in the two years preceding the study (defined as either two relapses or deterioration of at least 1 EDSS point). Treatment consisted of either 8 MIU of IFN beta-1b or placebo subcutaneously on alternate days over three years. The primary outcome was the time to confirmed neurologic deterioration, defined as a 1-point increase on the EDSS present for at least three months. In this study, for EDSS scores of 6.0 and higher, a change of 0.5 point was considered to be equal to 1.0 point for scores lower than 6.0. A prospectively planned interim analysis for efficacy was performed after all patients had completed at least 24 months of treatment. An alpha level of 0.0133 was predetermined for the intent-to-treat analysis of the primary end point.
Based on this interim analysis, the independent Advisory Board recommended that the study be stopped because there was a highly significant difference regarding the primary end point (p ≤0.0008). The delay in progression was within a range of 9–12 months. This effect was seen in patients both with and without superimposed relapses before or during the study, and it was consistent across all baseline EDSS levels studied. Significant reductions in time to require wheelchair use (EDSS 7.0), number of steroid courses given, and number of MS-related hospitalisations were also observed. Effects on relapse rate and MRI were consistent with the findings in the relapsing-remitting population. Whereas the mean lesion volume increased by about eight percent at two years, the mean lesion load in the active treatment group decreased by about five percent. In a subcohort of 125 patients a marked and significant reduction of new and enhancing lesions could be demonstrated for two six-month periods of frequent scanning (months 1–6 and 19–24). Additional MRI measures suggested, however, that this agent does not prevent the progression of cerebral atrophy. This study was the first to report a significant impact of any disease modifying treatment on the accumulation of disability in SPMS.
Strikingly, this favourable effect on disability progression could not be confirmed in a North American study of IFN beta-1b in SPMS. Even though this study tested the same therapeutic agent and dose, and both studies had similar (although not identical) entry criteria and study designs, no treatment benefit was seen on the time to confirmed progression of disability.
Effects on relapse- and MRI-related outcomes were consistently in favour of interferon beta-1b treated patients, a result consistent with earlier clinical trials.

In another study the efficacy and tolerability of interferon beta-1b was tested in 468 patients with a first clinical event suggestive of MS and additional asymptomatic MRI features. The treatment was well tolerated and, after two years, reduced the development of clinically definite MS (based on the occurrence of a new attack) by 50 percent and of McDonald MS (based on the occurrence of new lesions on MRI) by 46 percent. After a third year of observation, in which all patients who opted for this were on interferon beta-1b, it was found that early treatment with interferon beta-1b had reduced disability progression by 40 percent. 16 percent of patients who were treated early (from the start of the trial) had disability progression compared to 24 percent in the patients who were only treated after they had developed clinically definite MS or after two years of placebo treatment. These results should, however, be interpreted with care because the magnitude of benefit, even though statistically significant, is clinically small. 12 patients need to be treated early to avoid one additional patient showing disability worsening. These data are critically important to discuss with patients when considering start of therapy after the first manifestation of RRMS.

A large, but unblinded, study (“Incomin”) compared IFN beta-1b, 8 MIU on alternate days with once-weekly IM (Avonex ®) in patients with RRMS. In the same way as the “Evidence” study (see above), it concluded that relapses and MRI evidence of disease activity were less likely with more frequent dosing of IFN beta.