Table 3.
Efficacy of DMTs for MS
| DMT (trade name) | ARR reduction | Disability progressiona | Neuroradiologic outcomes |
|---|---|---|---|
| IFN beta-1b (Betaseron; Extavia) 0.25 mg dose [155] | 34% | No effect | 0.9% reduction in lesion area from baseline versus a 21.4% increase with placebo [134] |
| IFN beta-1a (Avonex) [156] | 18% for ITT population; 32% for completer population | 37% relative reduction in 24-week CDP by end of year 2 [135] | Reduction in number of Gd+ lesions (0.80 vs. 1.65) and volume of Gd+ lesions per patient (74.1 vs. 122.4 mm3) |
| IFN beta-1a (Rebif) [157] | 29% (22 mcg); 32% (44 mcg) | 23% (22 mcg) and 31% (44 mcg) relative reduction in ≥12-week CDP [158] | Median 1.2% (22 mcg) and 3.8% (44 mcg) decrease in T2 lesion burden versus a 10.9% increase with placebo. Reduced the number of T2 active lesions by 67% (22 mcg) and 78% (44 mcg) |
| Peginterferon beta-1a (Plegridy) [159] | 36% at 1 year | 38% relative reduction in 12-week CDP and 54% reduction in 24-week CDP at 1 year | 67% reduction in new or newly enlarging T2 lesions; 86% reduction in Gd+ lesions; 53% reduction in new T1 hypointense lesions at 1 year |
| Glatiramer acetate (Copaxone; Glatopa) [160] | 29% | No effect | 54% reduction in new or newly enlarging T2 lesions; 41% reduction in new T1 hypointense lesions; 61% reduction in mean Gd+ lesions [161] |
| Dimethyl fumarate (Tecfidera) [162] | 49% | 29% reduction in 24-week CDP | 83% reduction in Gd+ lesion activity; 78% reduction in new or newly enlarging T2 hyperintense lesions; 65% reduction in new nonenhancing T1 lesions |
| Teriflunomide (Aubagio) [163, 164] | 32–36% | 30–32% reduction in 12-week CDP | 80% reduced risk of Gd+ lesions; 67% reduction in total lesion volume; 31% reduction in T1 lesion volume; 77% reduction in T2 lesion volume [163] |
| Fingolimod (Gilenya) [165–167] | 48–54% [165, 166] 38–52% versus IFN beta-1a 30 mcg/week IM over 1 year [167] |
Data equivocal: FREEDOMS: 30% reduction in 12-week CDP [165]; no statistically significant effect in FREEDOMS II [166] No statistically significant effect in 12-week CDP versus IFN beta-1a 30 mcg/week IM over 1 year [167] |
FREEDOMS: fewer Gd+ lesions (0.2 vs. 1.1) and new or newly enlarging T2 hyperintense lesions (2.5 vs. 9.8) [165] Data confirmed in FREEDOMS II [166] Fewer Gd+ lesions (0.2 vs. 0.5) and new or newly enlarging T2 hyperintense lesions (1.7 vs. 2.6) versus IFN beta-1a 30 mcg/week IM over 1 year [167] |
| Daclizumab beta (Zinbryta) [92, 168]b | SELECT: 54% over 1 year [92] DECIDE: 45% versus IFN beta-1a 30 mcg/week IM over 144 weeks [168] |
SELECT: 57% risk reduction in 12- and 76% reduction in 24-week CDP over 1 year [81, 92] DECIDE: 27% risk reduction in 24-week CDP versus IFN beta-1a 30 mcg/week IM over 144 weeks [168] |
SELECT: over 1 year: 85% reduction in odds of new Gd+ lesions; 70% reduction in number of new or newly enlarging T2 hyperintense lesions [92] DECIDE: 75% reduction in odds of Gd+ lesion activity and 54% reduction in number of new or newly enlarging T2 hyperintense lesions over 96 weeks versus IFN beta-1a 30 mcg/week IM [168] |
| Alemtuzumab (Lemtrada) | Treatment-naive patients | ||
| CAMMS223: 69 and 66% in relapse risk over 3 and 5 years, respectively, versus IFN beta-1a 44 mcg SC three times per week [37, 169] CARE-MS I: 55% in relapse risk over 2 years versus IFN beta-1a 44 mcg SC three times per week [170] |
CAMMS223: 75 and 69% risk reduction over 3 and 5 years, respectively, versus IFN beta-1a 44 mcg SC three times per week [37, 169] CARE-MS I: No statistically significant effect over 2 years versus IFN beta-1a 44 mcg SC three times per week [170] |
Improvement in lesion load on T2-weighted MRI, and cerebral volume on T1-weighted MRI in CAMMS223 [169] CARE-MS I: reduced the proportions of patients with Gd+ lesions (7% alemtuzumab vs. 19% IFN beta-1a 44 mcg SC three times per week) and new or newly enlarging T2 hyperintense lesions (48 vs. 58%) |
|
| Treatment-experienced patients | |||
| CARE-MS II: 49% in relapse risk versus IFN beta-1a 44 mcg SC three times per week [105] | CARE-MS II: 42% reduction in 6-month risk versus IFN beta-1a 44 mcg SC three times per week | No between-group difference on T2 lesion volume; reduced the proportions of patients with Gd+ lesions (9% alemtuzumab vs. 23% IFN beta-1a 44 mcg SC three times per week) and new or newly enlarging T2 hyperintense lesions (46 vs. 68%) | |
| Natalizumab (Tysabri) [171] | AFFIRM: 68% | AFFIRM: 42% risk reduction in 12-week CDP; 54% risk reduction in 24-week CDP | AFFIRM: 92% fewer Gd+ lesions and 83% reduction in new or newly enlarging T2 hyperintense lesions |
| Ocrelizumab (Ocrevus) [120] | OPERA I: 46% versus IFN beta-1a OPERA II: 47% versus IFN beta-1a |
OPERA I and II: 40% risk reduction in 12- and 24-week CDP versus IFN beta-1a | OPERA I: 94% reduction in Gd+ lesions; 77% reduction in new or newly enlarging T2 hyperintense lesions versus IFN beta-1a OPERA II: 95% reduction in Gd+ lesions; 83% reduction in new or newly enlarging T2 hyperintense lesions versus IFN beta-1a |
| Mitoxantrone (Novantrone) [172, 173] | 63% of relapse risk [172] | 70% reduction in 24-week CDP [173] | Gd+ lesions (0 vs. 16% on placebo); mean increase in T2 lesions: 0.29 in the mitoxantrone group and 1.94 in the placebo group [172] |
Efficacy data are over 2 years and relative to placebo unless otherwise stated
ARR annualized relapse rate, CDP confirmed disability progression, DMT disease-modifying therapy, Gd + gadolinium-enhancing, IFN interferon, IM intramuscular, ITT intention-to-treat, MRI magnetic resonance imaging, MS multiple sclerosis, SC subcutaneous
aDisability progression data are significant unless stated otherwise
bFormerly daclizumab high-yield process (approved as ZINBRYTA®), which has a different form and structure than an earlier form of daclizumab