Home > Strength of evidence - Drug Class...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

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

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Appendix EStrength of evidence

Key Question 1: Evidence profile of the comparative efficacy of disease- modifying treatments for patients with multiple sclerosis

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 effectiveness of Interferon beta-1b SC (Betaseron®) vs Interferon beta-1a IM (Avonex®) on relapse-related outcomes – RRMS
% Relapse Free 2 head-to- head trials/278MediumConsistentDirectImpreciseBetaseron superior to Avonex RR=1.51 (1.11 to 2.07)Moderate
2 systematic reviewsMediumConsistentIndirectImpreciseBayesian meta-analysis %relapse-free RR, 1.48 (1.11, 2.02)
Outcome 2. Comparative effectiveness of Interferon beta-1b SC (Betaseron®) vs Interferon beta-1a IM (Avonex®) on disease progression outcomes – RRMS
1 head-to- head trial of dp/188; 3 H-to-H trials of EDSS change/325MediumInconsistentDirectImprecise% progressed: Betaseron superior to Avonex i 30% vs 13%, p=0.003; EDSS changea no difference −0.330(−0.686–0.025), I2=59.9%Low
2 systematic reviewsIndirectBayesian meta-analysis progression rate: Betaseron superior to Avonex RR, 0.48 (0.27–0.86)
Outcome 3. Comparative effectiveness of Interferon beta-1a IM (Avonex®) vs Interferon beta-1a SC (Rebif®) on Relapse-related outcomes – RRMS
2 head-to- head trials/767MediumConsistentDirect---% Relapse free: Rebif superior to Avonex (56–57% vs 20–48Moderate
2 systematic reviews of 3 PCTsIndirectBayesian MA RR=1.22 (1.06–1.41)
Outcome 4. Comparative effectiveness of Interferon beta-1a IM (Avonex®) vs Interferon beta-1a SC (Rebif®) on Disease progression outcomes – RRMS
3 head-to- head trials/814 % progressed 1HtoH/677 EDSS 2HtoH/137MediumConsistentDirectImprecise% dprogressed: no difference (54% vs 57%); EDSS:Moderate
2 systematic reviews of 3 PCTsIndirect% progressed: Bayesian meta-analysis: RR 1.05 (0.93–1.22)
Outcome 5. Comparative effectiveness of Interferon beta-1b SC (Betaseron®) vs Interferon beta-1a SC (Rebif®) on relapse-related outcomes – RRMS
2 head-to- head trials/391 % relapse freeMediumConsistentDirectImpreciseRR 1.51 (1.11 to 2.07)Moderate
2 systematic reviews of 3 PCTsIndirectBayesian meta-analysis RR 0.85 (0.56 – 1.25)
Outcome 6. Comparative effectiveness of Interferon beta-1b SC (Betaseron®) vs Interferon beta-1a SC (Rebif®) on disease progression outcomes – RRMS
3 head-to- head trials/438 %progressed: 1 HtoH/301 EDSS 2HtoH/137MediumInconsistentDirectImprecise% progressed: no difference 36% vs 33%; EDSS change −0.1 to −0.7 vs −0.3 to −0.4Moderate
2 systematic reviews of 3 PCTsIndirectBayesian meta-analysis progression rate RR= 1.18 (0.80, 1.71) and EDSS changea −0.30 (−0.60, 0.015)
Outcome 7. Comparative effectiveness of glatiramer actetate vs Interferon ® or placebo on relapse and disease progression outcomes – RRMS
2 head-to- head trials/3008MediumConsistentDirectImpreciseAnnualized relapse rate (0.29–0.34 vs 0.30–0.33), p=0.42–0.83; % relapse free (59–62% vs 58062% ), p=0.17–0.96; disease progression (8.7–21% vs 11.7–27% interferons), p=0.12–0.71. Glatiramer superior to placebo in mean relapse rate [−0.64(−1.19 – 10.09)], no dif in % relapse- free (RR 1.23, p=0.086)Moderate
1MA and 1 SR of 3 PCTsIndirect
Outcome 8. Comparative effectiveness of natalizumab vs placebo on relapse, disease progression, and health-related quality of life outcomes – RRMS
2 placebo- controlled trials/2113LowConsistentIndirect---% progressed(17–23% vs 29%, p<0.001 to 0.02), annualized relapse rate (023-0.34 vs 0.73–0.75, p≤0.001), % relapse free 61–67% vs 37–41%, p<0.001), HRQofL physical component of SF-36 OR 1.47–1.54 (1.06–2.23)Moderate
Outcome 9. Comparative effectiveness of mitoxantrone vs placebo on disease progression outcomes – RRMS
1 placebo- controlled trial/51Medium---Indirect---Absolute difference in risk 30% (95% CI 8–52%), NNT=3Insufficient
Outcome 10. Comparative effectiveness of Interferon β vs placebo on relapse and disease progression outcomes – SPMS
5 placebo- controlled trials/3075MediumInconsistentIndirect---Betaseron superior to placebo in disease progression HR 0.79 (0.66–0.93; Avonex superior to placebo in MSFC (−0.362 vs −0.495, p=0.033)
Interferon β superior to placebo in ARR Betaseron:0.16–0.44 vs 0.28 – 0.64, p=0.002–0.009
Rebif: RR 0.69 (0.56–0.85) and RR=0.9(0.64–1.27) Avonex ARR 0.2 vs 0.3, p=0.008
Moderate
Outcome 11. Comparative effectiveness of Interferon β vs placebo on relapse and disease progression outcomes – PPMS
1 placebo- controlled trial/50Medium---Indirect---no difference in time to sustained progressionLow

Key Question 4: Evidence profile of the comparative effectiveness of disease modifying treatments for patients with a clinically isolated syndrome

Domains pertaining to strength of evidenceMagnitude of effectStrength of evidence
Drug; Number of studies; Number of subjectsRisk of bias (design/quality)ConsistencyDirectnessPrecisionEstimate of effecta (95% CI)High, moderate, low, insufficient
Outcome: Progression to clinically definite multiple sclerosis
Avonex; 2 fair quality placebo- controlled trials; 600MediumConsistentIndirectPrecise0.56 (0.38 to 0.81)
0.63 (0.46 to 0.85)
Low
Rebif; 1 fair-quality placebo-controlled trial; 3090.65 (0.45 to 0.94)
Betaseron; 1 good quality placebo- controlled trial; 4680.50 (0.36 to 0.70)
Glatiramer; 1 fair quality placebo-controlled trial; 4810.55 (0.40 to 0.77)
a

Relative risk or hazard ratio.

Key Question 5: Evidence profile of the comparative harm of disease-modifying treatments for patients with multiple sclerosis

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

4 PCT
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)
Low
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
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.
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.

Download

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...