Cochrane · systematic review · CD011381
Immunomodulators and immunosuppressants for relapsing‐remitting multiple sclerosis: a network meta‐analysis
Gonzalez-Lorenzo, M, Ridley, B, Minozzi, S, et al. · Cochrane Database of Systematic Reviews · 2024 · Cochrane Library
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
94
current version
GRADE rated
82
No studies
12
Included studies
NR
No studies 12 · 12.8%Ungraded 0 · 0%Very low 34 · 36.2%Low 26 · 27.7%Moderate 18 · 19.1%High 4 · 4.3%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
Show all 2 versionsRelapses at 12 months
Population: Patients with RRMS Interventions: Azathioprine, daclizumab, fingolimod, glatiramer acetate, Immunoglobulins, interferon beta 1a ‐1b, interferon beta‐1b (Betaferon), interferon beta‐1a (Avonex, Rebif), pegylated interferon beta‐1a, mitoxantrone, natalizumab, teriflunomide Comparator (reference): Placebo Outcome: Relapses at 12 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies/participants) | no estimate extracted | NR | No studies |
Azathioprine (Direct evidence; 1 RCT; 59 participants) | RR 0.91 [0.58, 1.43] | 1 study · 59 participants | Very low Downgraded: risk of bias |
Daclizumab (Direct evidence; 1 RCT; 621 participants) | RR 0.55 [0.42, 0.73] | 1 study · 621 participants | Moderate Downgraded: risk of bias |
Fingolimod No direct evidence | RR 0.48 [0.39, 0.57] | NR | Moderate Downgraded: risk of bias |
Glatiramer acetate (Direct evidence; 2 RCTs; 1454 participants) | RR 0.64 [0.55, 0.75] | 2 studies · 1454 participants | Low Downgraded: risk of bias |
Immunoglobulins (Direct evidence; 2 RCTs; 91 participants) | RR 0.6 [0.47, 0.79] | 2 studies · 91 participants | Moderate Downgraded: risk of bias |
Interferon beta 1a‐1b No direct evidence | RR 1.42 [0.78, 2.6] | 1 participants | Very low Downgraded: risk of bias |
Interferon beta‐1b (Betaferon) No direct evidence | RR 0.82 [0.5, 1.33] | 1 participants | Very low Downgraded: risk of bias |
Interferon beta‐1a (Avonex, Rebif) (Direct evidence; 1 RCT; 560 participants) | RR 0.76 [0.68, 0.85] | 1 study · 560 participants | Low Downgraded: risk of bias |
Pegylated interferon beta‐1a (Direct evidence; 1 RCT; 1512 participants) | RR 0.68 [0.56, 0.82] | 1 study · 1512 participants | Low Downgraded: risk of bias |
Mitoxantrone (Direct evidence; 1 RCT; 51 participants) | RR 0.4 [0.21, 0.74] | 1 study · 51 participants | Low Downgraded: risk of bias |
Natalizumab (Direct evidence; 1 RCT; 942 participants) | RR 0.52 [0.43, 0.63] | 1 study · 942 participants | High |
Teriflunomide (Direct evidence; 1 RCT; 1169 participants) | RR 0.66 [0.55, 0.78] | 1 study · 1169 participants | Low Downgraded: risk of bias |
Placebo | no estimate extracted | NR | No studies |
Relapses at 24 months
Population: Patients with RRMS Interventions: alemtuzumab, azathriopine, cladribine, dimethylfumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta 1a‐1b, interferon beta‐1b (Betaferon), interferon beta‐1a (Avonex, Rebif, laquinimod, mitoxantrone, natalizumab, ponesimod, teriflunomide Comparator (reference): Placebo Outcome: Relapses at 24 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies/participants) | no estimate extracted | NR | No studies |
Alemtuzumab No direct evidence | RR 0.57 [0.47, 0.68] | NR | High |
Azathioprine (Direct evidence; 1 RCT; 59 participants) | RR 0.77 [0.51, 1.18] | 1 study · 59 participants | Very low Downgraded: risk of bias |
Cladribine (Direct evidence; 1 RCT; 1326 participants) | RR 0.53 [0.44, 0.64] | 1 study · 1326 participants | High |
Dimethylfumarate (Direct evidence; 2 RCTs; 2307 participants) | RR 0.62 [0.55, 0.7] | 2 studies · 2307 participants | Moderate Downgraded: risk of bias |
Fingolimod (Direct evidence; 2 RCTs; 2355 participants) | RR 0.54 [0.48, 0.6] | 2 studies · 2355 participants | Moderate Downgraded: risk of bias |
Glatiramer acetate (Direct evidence; 3 RCsT; 1014 participants) | RR 0.84 [0.76, 0.93] | 3 participants | Moderate Downgraded: risk of bias |
Immunoglobulins (Direct evidence; 2 RCTs; 192 participants) | RR 0.73 [0.59, 0.9] | 2 studies · 192 participants | Low Downgraded: risk of bias |
Interferon beta 1a‐1b No direct evidence | RR 1.21 [0.66, 2.19] | 1 participants | Very low Downgraded: risk of bias |
Interferon beta‐1b (Betaferon) (Direct evidence; 1 RCT; 372 participants) | RR 0.85 [0.76, 0.94] | 1 study · 372 participants | Low Downgraded: risk of bias |
Interferon beta‐1a (Avonex, Rebif) (Direct evidence; 3 RCTs; 1629 participants) | RR 0.84 [0.78, 0.91] | 1 study · 3 participants | Moderate Downgraded: risk of bias |
Laquinimod (Direct evidence; 3 RCTs; 3457 participants) | RR 0.83 [0.76, 0.91] | 3 studies · 3457 participants | Low Downgraded: risk of bias |
Mitoxantrone (Direct evidence; 1 RCT; 51 participants) | RR 0.47 [0.27, 0.8] | 1 study · 51 participants | Low Downgraded: risk of bias |
Natalizumab (Direct evidence; 1 RCT; 942 participants) | RR 0.56 [0.48, 0.65] | 1 study · 942 participants | High |
Ponesimod No direct evidence | RR 0.58 [0.48, 0.7] | NR | Moderate Downgraded: risk of bias |
Teriflunomide (Direct evidence; 1 RCT; 1088 participants) | RR 0.82 [0.71, 0.94] | 1 study · 1088 participants | Very low Downgraded: risk of bias |
Placebo | no estimate extracted | NR | No studies |
Relapses at 36 months
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies/participants) | no estimate extracted | NR | No studies |
Interferon beta‐1b (Betaferon) (Direct evidence; 2 RCTs; 403 participants) | RR 0.86 [0.67, 1.11] | 1 study · 2 participants | Very low |
Placebo | no estimate extracted | NR | No studies |
Disability at 24 months
Population: Patients with RRMS Interventions: Alemtuzumab, azathioprine, cladribine, dimethylfumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta 1a‐1b, interferon beta‐1b (Betaferon), interferon beta‐1a (Avonex, Rebif), laquinimod, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod, teriflunomide Comparator (reference): Placebo Outcome: Disability at 24 months Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies and participants) | no estimate extracted | NR | No studies |
Alemtuzumab No direct evidence | RR 0.67 [0.46, 0.99] | NR | Low Downgraded: risk of bias |
Azathioprine (Direct evidence; 1 RCT; 59 participants) | RR 0.6 [0.22, 1.63] | 1 study · 59 participants | Very low Downgraded: risk of bias |
Cladribine (Direct evidence; 1 RCT; 1326 participants) | RR 0.72 [0.56, 0.91] | 1 study · 1326 participants | Low Downgraded: risk of bias |
Dimethylfumarate (Direct evidence; 2 RCTs; 2307 participants) | RR 0.65 [0.55, 0.77] | 2 studies · 2307 participants | Low Downgraded: risk of bias |
Fingolimod (Direct evidence; 2 RCTs; 2355 participants) | RR 0.68 [0.56, 0.83] | 2 studies · 2355 participants | Low Downgraded: risk of bias |
Glatiramer acetate (Direct evidence; 3 RCTs; 1014 participants) | RR 0.74 [0.61, 0.89] | 3 studies · 1014 participants | Very low Downgraded: risk of bias |
Immunoglobulins (Direct evidence; 2 RCTs; 190 participants) | RR 0.75 [0.41, 1.37] | 2 studies · 190 participants | Very low Downgraded: risk of bias |
Interferon beta 1a‐1b No direct evidence | RR 3.19 [0.31, 33.21] | 1 participants | Very low Downgraded: risk of bias |
Interferon beta‐1b (Betaferon) (Direct evidence; 1 RCT; 372 participants) | RR 0.77 [0.62, 0.94] | 1 study · 372 participants | Low Downgraded: risk of bias |
Interferon beta‐1a (Avonex, Rebif) (Direct evidence; 2 RCTs; 1069 participants) | RR 0.92 [0.73, 1.16] | 1 study · 2 participants | Low Downgraded: risk of bias |
Laquinimod (Direct evidence; 3 RCTs; 3451 participants) | RR 0.78 [0.63, 0.96] | 3 studies · 3451 participants | Very low Downgraded: risk of bias |
Mitoxantrone (Direct evidence; 1 RCT; 51 participants) | RR 0.2 [0.05, 0.83] | 1 study · 51 participants | Very low Downgraded: risk of bias |
Natalizumab (Direct evidence; 1 RCT; 942 participants) | RR 0.59 [0.46, 0.75] | 1 study · 942 participants | Moderate Downgraded: risk of bias |
Ocrelizumab No direct evidence | RR 0.61 [0.41, 0.9] | NR | Very low Downgraded: risk of bias |
Ofatumumab No direct evidence | RR 0.54 [0.38, 0.77] | NR | Very low Downgraded: risk of bias |
Ozanimod No direct evidence | RR 1.19 [0.74, 1.91] | NR | Very low Downgraded: risk of bias |
Ponesimod No direct evidence | RR 0.63 [0.41, 0.96] | NR | Very low Downgraded: risk of bias |
Teriflunomide (Direct evidence; 1 RCT; 1088 participants) | RR 0.76 [0.61, 0.95] | 1 study · 1088 participants | Very low Downgraded: risk of bias |
Placebo | no estimate extracted | NR | No studies |
Discontinuation due to adverse effects
Population: Patients with RRMS Interventions: Alemtuzumab, azathioprine, cladribine, daclizumab, dimethylfumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta 1a‐1b, interferon beta‐1b (Betaferon), interferon beta‐1a (Avonex, Rebif), laquinimod, pegylated interferon beta1a, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod, teriflunomide Comparator (reference): Placebo Outcome: Treatment discontinuation due to adverse events Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies/participants) | no estimate extracted | NR | No studies |
Alemtuzumab No direct evidence | OR 0.39 [0.19, 0.79] | NR | Moderate Downgraded: risk of bias |
Azathioprine (Direct evidence; 1 RCT; 54 participants) | OR 6.26 [0.67, 58.05] | 1 study · 54 participants | Very low Downgraded: risk of bias |
Cladribine (Direct evidence; 1 RCT; 1326 participants) | OR 1.38 [0.46, 4.15] | 1 study · 1326 participants | Low Downgraded: risk of bias |
Daclizumab (Direct evidence; 1 RCT; 600 participants) | OR 2.55 [1.4, 4.63] | 1 study · 600 participants | Moderate Downgraded: risk of bias |
Dimethylfumarate (Direct evidence; 2 RCTs; 2300 participants) | OR 1.35 [0.94, 1.95] | 2 studies · 2300 participants | Low Downgraded: risk of bias |
Fingolimod (Direct evidence; 2 RCTs; 2355 participants) | OR 1.84 [1.31, 2.57] | 2 studies · 2355 participants | Moderate Downgraded: risk of bias |
Glatiramer acetate (Direct evidence; 4 RCTs; 2419 participants) | OR 1.48 [1.02, 2.14] | 4 studies · 2419 participants | Moderate Downgraded: risk of bias |
Immunoglobulins (Direct evidence; 3 RCTs; 243 participants) | OR 2.49 [0.37, 16.5] | 3 studies · 243 participants | Very low Downgraded: risk of bias |
Interferon beta 1a‐1b No direct evidence | OR 3.02 [0.27, 33.65] | 1 participants | Very low Downgraded: risk of bias |
Interferon beta‐1b (Direct evidence; 1 RCT; 372 participants) | OR 2.27 [1.05, 4.91] | 1 study · 372 participants | Low Downgraded: risk of bias |
Interferon beta‐1a (Direct evidence; 2 RCTs; 1457 participants) | OR 1.48 [0.99, 2.2] | 1 study · 2 participants | Moderate Downgraded: risk of bias |
Laquinimod (Direct evidence; 3 RCTs; 3457 participants) | OR 1.46 [1, 2.15] | 3 studies · 3457 participants | Moderate Downgraded: risk of bias |
Pegylated interferon beta‐1a (Direct evidence; 1 RCT; 1512 participants) | OR 3.58 [1.47, 8.73] | 1 study · 1512 participants | Very low Downgraded: risk of bias |
Natalizumab (Direct evidence; 1 RCT; 939 participants) | OR 1.57 [0.81, 3.05] | 1 study · 939 participants | Moderate Downgraded: risk of bias |
Ocrelizumab No direct evidence | OR 0.82 [0.42, 1.6] | NR | Low Downgraded: risk of bias |
Ofatumumab No direct evidence | OR 2 [1.05, 3.81] | NR | Low Downgraded: risk of bias |
Ozanimod No direct evidence | OR 1.01 [0.52, 1.95] | NR | Low Downgraded: risk of bias |
Ponesimod No direct evidence | OR 5.04 [2.15, 11.82] | NR | Very low Downgraded: risk of bias |
Teriflunomide (Direct evidence; 2 RCTs; 2253 participants) | OR 1.82 [1.19, 2.79] | 2 studies · 2253 participants | Moderate Downgraded: risk of bias |
Placebo | no estimate extracted | NR | No studies |
Serious adverse events
Population: Patients with RRMS Interventions: Alemtuzumab, cladribine, daclizumab, dimethylfumarate, fingolimod, glatiramer acetate, interferon beta‐1b (Betaferon), interferon beta‐1a (Avonex, Rebif), laquinimod, pegylated interferon beta‐1a, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod, teriflunomide Comparator (reference): Placebo Outcome: Serious adverse events Setting(s): Outpatient
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intervention (no. of studies/participants) | no estimate extracted | NR | No studies |
Alemtuzumab No direct evidence | OR 1.52 [0.94, 2.48] | NR | Very low Downgraded: risk of bias |
Cladribine (Direct evidence; 1 RCT; 1326 participants) | OR 1.39 [0.8, 2.4] | 1 study · 1326 participants | Very low Downgraded: risk of bias |
Daclizumab (Direct evidence; 1 RCT; 600 participants) | OR 1.9 [1.21, 2.99] | 1 study · 600 participants | Low Downgraded: risk of bias |
Dimethylfumarate (Direct evidence; 2 RCTs; 2300 participants) | OR 1.04 [0.71, 1.52] | 2 studies · 2300 participants | Low Downgraded: risk of bias |
Fingolimod (Direct evidence; 2 RCTs; 2355 participants) | OR 0.86 [0.64, 1.13] | 2 studies · 2355 participants | Low Downgraded: risk of bias |
Glatiramer acetate (Direct evidence; 3 RCTs; 2371 participants) | OR 0.94 [0.68, 1.28] | 3 studies · 2371 participants | Low Downgraded: risk of bias |
Interferon beta‐1b (Betaferon) No direct evidence | OR 0.92 [0.55, 1.54] | 1 participants | Moderate Downgraded: risk of bias |
Interferon beta‐1a (Rebif, Avonex) (Direct evidence; 1 RCT; 897 participants) | OR 1.21 [0.88, 1.67] | 1 study · 897 participants | Very low Downgraded: risk of bias |
Laquinimod (Direct evidence; 3 RCTs; 3457 participants) | OR 1.25 [0.92, 1.7] | 3 studies · 3457 participants | Very low Downgraded: risk of bias |
Pegylated interferon beta‐1a (Direct evidence; 1 RCT; 1512 participants) | OR 1.08 [0.59, 1.96] | 1 study · 1512 participants | Very low Downgraded: risk of bias |
Mitoxantrone (Direct evidence; 1 RCT; 53 participants) | OR 0.89 [0.02, 47.22] | 1 study · 53 participants | Very low Downgraded: risk of bias |
Natalizumab (Direct evidence; 1 RCT; 939 participants) | OR 1.24 [0.73, 2.09] | 1 study · 939 participants | Low Downgraded: risk of bias |
Ocrelizumab No direct evidence | OR 1 [0.58, 1.72] | NR | Very low Downgraded: risk of bias |
Ofatumumab No direct evidence | OR 1.52 [0.89, 2.57] | NR | Very low Downgraded: risk of bias |
Ozanimod No direct evidence | OR 1.5 [0.85, 2.64] | NR | Very low Downgraded: risk of bias |
Ponesimod No direct evidence | OR 1.24 [0.66, 2.35] | NR | Very low Downgraded: risk of bias |
Teriflunomide (Direct evidence; 2 RCTs; 2253 participants) | OR 1.16 [0.81, 1.64] | 2 studies · 2253 participants | Very low Downgraded: risk of bias |
Placebo | no estimate extracted | NR | No studies |