CHAMPS CHAMPIONS AND ETOMS

CHAMPS 383 patients with very recent (27 days) CIS involving the optic nerve. Patients had to have 2 or more clinically silent lesions at least 3 mm in diameter, one ovoid or periventricular. Conversion to CDMS was a new event lasting at least 48 hours or deterioration of at least 1.5 points on the EDSS. All patients got three day Solumedrol pulse with taper at onset of study. Study was terminated after a positive interim analysis. Mean followup was 31 months. With interferon B1a (Avonex) the likelihood of developing MS was reduced 44 % (p<0.002). Posthoc analysis looked at high and low risk groups. The probability of CDMS in patients getting placebo was 50 %, 64 % in a high risk group (n=40) and 46 % in non high risk group (n=150). High risk was defined as nine or more lesions on T2 or one or more Gadolinium enhancing lesions. Only 20 % of Avonex group had CDMS at two years. Avonex reduced CDMS by 63 % at year 2, and 66 % by year 3. NTT=6.7 to prevent one patient from developing CDMS. Critiques: questionable blinding by treating physicians who followed side effects of patients. Disability and relapse rate were not applicable as points of study. No information is given on brain atrophy. AE's-- flu like reaction was 54 %, depression 20 % (v. 26, and 13 % respectively). Patients withdrawn from study did not get f/u scans. Chance of getting CDMS or dropping out was 64 % in placebo group, 51 % in active group. Class I study, category A.

The extension trial open label CHAMPIONS the original patients were all given Avonex (early and delayed treatment groups). N of the groups was 100, 103 , respectively. Thus slightly more than half the patients entered CHAMPIONS and they were treated UP TO five years (ie. not all made it that long). In the 2 groups, the respective rate of CDMS was 36 and 48 %. The rate of CDMS was decreased by 35 % in the immediate treatment group (looking at numbers could be 25 %). The NTT was 8 to treat early to prevent CDMS at five years. The mean number of relapses over five years was .9 and 1.7, respectively. The median number of T2 lesions was 3.5 and 6.0 respectively.

ETOMS studied Rebif in patients with unifocal or multifocal neurologic syndromes. Patients had at least 4 lesions on T2, or 3 if one was incfratentorial or enhancing. The primary measure was conversion to CDMS. Initial steroids were not given uniformly. Entry was allowed up to three months post event, and polysymptomatic patients were included. 39 % were in fact multifocal. The primary endpoint was conversion to CDMS. Like CHAMPS, effect of treating physician blinidng was criticized. There were 309 patients, 154 in each group and one patient thrown out). In the Rebif group, 34 % converted to CDMS and in the placebo group, 45 % converted at two years. The benefit was about 25 %, with NTT at 9.1 to prevent one CDMS at 2 years. The relapse rates were .33 and .43, respectively. The median number of active T2 lesions was 2 and 3, respectively.Actual data, percent, for placebo and rebif group, respectively: proportion converting to CDMS 45, 34; mean annual relapse rate: .43, .33 {Note: this is much lower than in pivotal betaseron trial}; median EDSS change to year 2: 0,0; median SNRS baseline to year 2: 0,0; median active T2 lesions per scan: 3,2; median enhancing lesions per scan: 0, 0.5; median change in T2 lesion volume from baseline to year 2: 8.8; -13.0. Class I study, Category A.