Table 2.
Clinical Trials Testing DMT in High-Risk CIS Patients.
| Abbreviated Study Name | Study design and Duration | N | Inclusion Criteria | Treatments | Primary End Points | Percentage With CDMS At Study End | Time to CDMS (Days for 25th-30th percentile) | MRI Changes |
|---|---|---|---|---|---|---|---|---|
| CHAMPS71 | Randomized, double blind 3 years (terminated early due to efficacy in preplanned interim analysis) | 383 | CIS onset within 4 weeks, ≥2 silent MRI brain lesions (≥3 mm diameter, with ≥1 lesion either periventricular or ovoid) | IM IFNβ-1a (Avonex) 30 μg q week versus placeboa | Time to CDMS | 35% on IFNβ-1a 50% on placebo (P = .002) | 809 on IFNβ-1a 397 on placebo | Gd-enhancing lesions, new or enlarging T2 lesions, increase in lesion volume significantly lower with IFNβ-1a |
| ETOMS67 | Randomized, double blind 2 years | 309 | CIS onset within 3 months, ≥4 silent MRI brain lesions (≥3 lesions if there is an infratentorial or Gd-enhancing lesion) | SC IFNβ-1a (Rebif) 22 μg q weekb versus placebo | Time to CDMS | 34% on IFNβ-1a 45% on placebo (p = 0.047) | 569 on IFNβ-1a 252 on placebo | New T2 lesions and increase in lesion load significantly lower with IFNβ-1a |
| BENEFIT40, 76 | Randomized, double blind 2 years | 468 | CIS onset within 60 days, ≥2 silent MRI brain lesions (≥3 mm in diameter, with ≥1 lesion ovoid, periventricular, or infratentorial) | SC IFNβ-1b (Betaseron) 250 μg qod versus placebo | Time to CDMS | 28% on IFNβ-1b 45% on placebo (P < .0001) | 618 on IFNβ-1b 255 on placebo | New T2 lesions, Gd-enhancing lesions, volume of Gd-enhancing lesions significantly lower with IFNβ-1b |
| PreCISe77 | Randomized, double blind 2.3 years (mean) | 481 | CIS onset within 90 days, ≥2 silent MRI brain lesions ≥6 mm in diameter | SC GA (Copaxone) 20 mg daily versus placebo | Time to CDMS | 25% on GA 43% on placebo (P = .0005) | 722 on GA 336 on placebo | New T2 lesions and volume, Gd-enhancing lesions, T1 hypointense lesions signficantly lower with GA |
Abbreviations: CDMS, clinically definite multiple sclerosis; CIS, clinically isolated syndrome; DMT, disease-modifying therapy; FDA, Food and Drug Administration; GA, glatiramer acetate; Gd, gadolinium; IFN, interferon; IM, intramuscular; MRI, magnetic resonance imaging; q, every; SC, subcutaneous.
a All patients treated with high-dose methylprednisone and an 11-day prednisone taper prior to initiating study drug.
b Lower quantity and less frequent than the current FDA-approved dose.
Modified from Connor and Smith.104 Reproduced with permission from Consensus Medical Communications.