Table 2.

Summary of PRISMS, INCOMIN, EVIDENCE and ADVANCE trials

PRISMS24 – Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis
Inclusion criteria	Clinically definite RRMS for ≥1 year; ≥2 relapses in preceding 2 years, and baseline EDSS scores of 0–5
Exclusion criteria	Previous systemic treatment with IFNs, lymphoid irradiation or cyclophosphamide or with other immunomodulatory or immunosuppressive therapy in previous 12 months
Intervention	IFNβ-1a (Rebif®) 22 or 44 µg SC TIW or placebo
Primary outcome	Relapse rate over the course of 2-year study
Summary of results	Relapse rates were reduced by 27% in the 22 µg IFNβ-1a intervention and 33% in the 44 µg IFNβ-1a intervention group compared to placebo group. IFNβ-1a interventions were also associated with an increased proportion of patients remaining relapse free, decreased change in EDSS scores and decreased time to first progression. MRI end points showed a decrease in total burden of disease (ΔT2 lesion volume), number of new/newly enlarging T2 lesions and number of T1 Gd-enhancing lesions with IFNβ-1a treatment compared to placebo. High-dose treatment (44 µg) showed more favorable outcomes compared to low-dose treatment (22 µg)
INCOMIN31 – Independent Comparison of Interferon
Inclusion criteria	Clinically definite RRMS; ≥2 clinically documented relapses during the preceding 2 years with no relapse (and no corticosteroid treatment) for at least 30 days before study entry and baseline EDSS score of 1–3.5
Exclusion criteria	Previous systemic treatment with IFNβ or treatment with other immunosuppressive or immunomodulatory drugs (except corticosteroids)
Intervention	IFNβ-1b (Betaseron®) 250 µg SC QAD or IFNβ-1a (Avonex®) 30 µg IM QW
Primary outcome	Proportion of patients who remained relapse free over the course of 2-year study
Summary of results	In the IFNβ-1b SC intervention group, 49% of patients remained relapse free compared to 33% in the IFNβ-1a IM intervention group. IFNβ-1b treatment was also associated with a decrease in ARR and 6-month sustained progression in EDSS. MRI end points showed an increase in the proportion of patients remaining free from new T2 lesions, remaining free from T1 Gd-enhancing lesions and showing no MRI activity with IFNβ-1b SC compared to IFNβ-1a IM treatment
EVIDENCE32 – Evidence of Interferon Dose-response-European North American Comparative Efficacy
Inclusion criteria	Clinically confirmed RRMS; ≥2 relapses in previous 2 years and baseline EDSS score of 0–5.5
Exclusion criteria	Previous treatment with IFNβ
Intervention	IFNβ-1a (Rebif®) 44 µg SC TIW or IFNβ-1a (Avonex®) 30 µg IM QW
Primary outcome	Proportion of patients who remained relapse free at ≥48 weeks
Summary of results	In the IFNβ-1a SC TIW intervention group, 56% of patients remained relapse free compared to 48% in the IFNβ-1a IM QW intervention group. IFNβ-1a SC TIW was also associated with a decrease in ARR and time to first relapse, but no difference was observed in EDSS progression. MRI end points showed a decrease in the number of new or enlarging T2 lesions in the IFNβ-1a SC TIW compared to the IFNβ-1a IM QW treatment
ADVANCE25 – Pegylated Interferon beta-1a for Relapsing–Remitting Multiple Sclerosis
Inclusion criteria	RRMS; ≥2 relapses in previous 3 years with at least one relapse in previous 12 months and baseline EDSS score of 0–5
Exclusion criteria	Progressive MS, previous treatment with IFNβ for >4 weeks or discontinuation <6 months before baseline
Intervention	PEG-IFNβ-1a Plegridy® 125 µg SC Q2W or Q4W or placebo
Primary outcome	ARR at 48 weeks
Summary of results	ARR were reduced by 36% in the PEG-IFN Q2W and 28% in the PEG-IFN Q4W intervention groups compared to the placebo group. PEG-IFNβ interventions were also associated with an increased proportion of patients remaining relapse free and a decreased proportion of patients showing 12-week sustained EDSS progression. MRI end points showed a decrease in total burden of disease (ΔT2 lesion volume), number of new/newly enlarging T2 lesions and number of T1 Gd-enhancing lesions with PEG-IFNβ treatment compared to placebo. More frequent injections (Q2W) showed more favorable outcomes compared to low-frequency injections (Q4W)

Abbreviations: ARR, annualized relapse rate; EDSS, expanded disability status scale; IFNβ, interferon beta; IM, intramuscular; MS, multiple sclerosis; PEG, polyethylene glycol; QAD, once every other day; QW, once weekly; Q2W, once every 2 weeks; Q4W, once every 4 weeks; RRMS, relapsing–remitting MS; MRI, magnetic resonance imaging; SC, subcutaneous; TIW, three times weekly.