Domains pertaining to strength of evidenceMagnitude of effectStrength of evidence
Number of studies; Number of subjectsRisk of bias (design/quality)ConsistencyDirectnessPrecisionSummary effect size (95% CI)High, moderate, low, insufficient
Outcome 1. Comparative harm of interferon beta-1b SC (Betaseron®) vs. interferon beta-1a SC (Rebif®). vs interferon beta-1a IM (Avonex®)
3H-toH/1166 RRMS

2 SR of 6 PCT in RRMS

5 PCT in SPMS/3075

1 SR in PPMS
ModerateConsistentIndirectImpreciseInjection site reaction least with Avonex 8.5% (4.5 to 15.2); Flu-like syndrome greatest with Avonex 62.2% (39.0 to 80.8); Fever greatest with Betaseron 33.3% (19.0 to 47.6); Overall withdrawal greatest with Betaseron 7.5% (3.7 to 11.2)Moderate
Outcome 2. Comparative safety of Interferon beta-1b SC (Betaseron®) vs. Interferon beta-1a SC (Rebif®) vs. Interferon beta-1a IM (Avonex®) on depression
Depression: 1 MA

ModerateConsistentIndirectImpreciseBetaseron vs Rebif 44 μg RR 0.72(0.40–1.29); Betaseron vs Avonex RR 0.79(0.42–1.48); Rebif vs Avonex RR 1.05(0.68–1.63)Moderate
Outcome 3. Comparative harm of glatiramer acetate vs. Interferon beta-1b SC (Betaseron®) or Interferon β-1a (Rebif ®)
2 H-to-H/3008ModerateConsistentDirectImpreciseinjection site reactions 58% vs 48% (1 trial), post-injection systemic responses 17% vs 0–5% (2 trials), influenza-like illness 1–6% vs 31–40%, elevated liver enzymes, 1–4% vs 6–11%, fever 4–5% vs 6–9%,,
Outcome 4. Comparative harm of mitoxantrone vs. placebo
1 SRModerateConsistentIndirect---amenorrhea 29% vs 0% p=0.0004,, LVEF <50% 2.18%, (95% CI 1.28–3.47%),, nausea with vomiting 62.3% vs 15.4% p<0.00001, Acute leukemia incidence 0.15% at 70mg/m2; Fatal congestive heart failure 0.15%, 95% CI 0.02–0.52%;;
Permanent amenorrhea associated with older age (OR 1.02, 10.1–1.04) and higher cumulative dose (OR 1.18, 1.10–1.27)
Outcome 5. Comparative harm of natalizumab vs. placebo
5 PCT/2578ModerateConsistentIndirect---55 cases of PML reported–estimated incidence is 1.0 per 1000 treated patients (95% CI, 0.2 to 2.8 per 1000)Moderate

From: Appendix E, Strength of evidence

Cover of Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis
Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report [Internet].
Smith B, Carson S, Fu R, et al.
Portland (OR): Oregon Health & Science University; 2010 Aug.
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.

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