Wise Young
04-16-2002, 08:47 PM
[S13.005] Evidence of Dose Response: Effects of Two Interferon Beta-1a Products on Relapse-Related Parameters in Multiple Sclerosis
Mohammad K. Sharief, EVIDENCE Study GroupÂ*London, United Kingdom
OBJECTIVE: To compare the effects of two interferon (IFN) beta-1a products on relapse-related parameters in patients with relapsing-remitting multiple sclerosis (RRMS).
BACKGROUND: Two IFN beta-1a products are available for the treatment of RRMS: Rebif® (Serono) and Avonex® (Biogen). The EVIDENCE study was designed to permit a direct comparison of these products. Key data from this prospective, randomised, assessor-blinded study have been presented elsewhere. This presentation describes in more detail results relating to relapses.
DESIGN/METHODS: 677 patients with RRMS were randomised to receive Rebif®, 44 mcg three times weekly (tiw), or Avonex®, 30 mcg once weekly (qw), for 24 weeks. To ensure that all relapses were detected, patients were contacted every 2 weeks throughout the study and were required to inform their physicians within 48 hours of the onset of each suspected relapse. The severity of each relapse was assessed and the functional systems affected were noted. In addition, the numbers of hospitalisations and steroid courses needed because of relapses were recorded. All assessing neurologists were blinded to treatment.
RESULTS: The proportion of patients remaining relapse-free throughout the 24 weeks of the study was 74.9% with Rebif® and 63.3% with Avonex® (p=0.001), and the mean number of relapses per patient was 0.29 with Rebif® and 0.40 with Avonex® (p=0.022). The mean time that elapsed before the first 20% of patients had their first relapse was 118 days with Rebif® and 89 days with Avonex® (p=0.001), and the hazard ratio for relapsing with Rebif® as opposed to Avonex® was 0.63 (p<0.001). The impact of Rebif® on relapses was greater than that of Avonex® for all relapse severity categories. Patients receiving Rebif® and Avonex® were similar with respect to the proportion of relapses affecting each functional system. Only one relapse [Avonex® patient) led to hospitalisation for a reason other than facilitation of steroid administration. The mean number of steroid courses needed per patient was 0.094 with Rebif® and 0.177 with Avonex® [p=0.004).
CONCLUSIONS: In this large, multicentre, randomised, assessor-blinded trial, Rebif®, 44 mcg tiw, had a significantly greater impact than Avonex®, 30 mcg qw, on several relapse-related outcomes, and was not associated with any new or dose-limiting safety concerns. The superiority of Rebif® was not due simply to suppression of mild relapses, but applied across all severity categories. These findings support the hypothesis that dosing schedule has a major impact on the efficacy of IFN beta-1a, and indicate that higher and more frequent doses of IFN beta-1a are beneficial in RRMS.
Supported By: Serono International SA.
Category - MS and Related Diseases
SubCategory - Therapeutic Trials
Mohammad K. Sharief, EVIDENCE Study GroupÂ*London, United Kingdom
OBJECTIVE: To compare the effects of two interferon (IFN) beta-1a products on relapse-related parameters in patients with relapsing-remitting multiple sclerosis (RRMS).
BACKGROUND: Two IFN beta-1a products are available for the treatment of RRMS: Rebif® (Serono) and Avonex® (Biogen). The EVIDENCE study was designed to permit a direct comparison of these products. Key data from this prospective, randomised, assessor-blinded study have been presented elsewhere. This presentation describes in more detail results relating to relapses.
DESIGN/METHODS: 677 patients with RRMS were randomised to receive Rebif®, 44 mcg three times weekly (tiw), or Avonex®, 30 mcg once weekly (qw), for 24 weeks. To ensure that all relapses were detected, patients were contacted every 2 weeks throughout the study and were required to inform their physicians within 48 hours of the onset of each suspected relapse. The severity of each relapse was assessed and the functional systems affected were noted. In addition, the numbers of hospitalisations and steroid courses needed because of relapses were recorded. All assessing neurologists were blinded to treatment.
RESULTS: The proportion of patients remaining relapse-free throughout the 24 weeks of the study was 74.9% with Rebif® and 63.3% with Avonex® (p=0.001), and the mean number of relapses per patient was 0.29 with Rebif® and 0.40 with Avonex® (p=0.022). The mean time that elapsed before the first 20% of patients had their first relapse was 118 days with Rebif® and 89 days with Avonex® (p=0.001), and the hazard ratio for relapsing with Rebif® as opposed to Avonex® was 0.63 (p<0.001). The impact of Rebif® on relapses was greater than that of Avonex® for all relapse severity categories. Patients receiving Rebif® and Avonex® were similar with respect to the proportion of relapses affecting each functional system. Only one relapse [Avonex® patient) led to hospitalisation for a reason other than facilitation of steroid administration. The mean number of steroid courses needed per patient was 0.094 with Rebif® and 0.177 with Avonex® [p=0.004).
CONCLUSIONS: In this large, multicentre, randomised, assessor-blinded trial, Rebif®, 44 mcg tiw, had a significantly greater impact than Avonex®, 30 mcg qw, on several relapse-related outcomes, and was not associated with any new or dose-limiting safety concerns. The superiority of Rebif® was not due simply to suppression of mild relapses, but applied across all severity categories. These findings support the hypothesis that dosing schedule has a major impact on the efficacy of IFN beta-1a, and indicate that higher and more frequent doses of IFN beta-1a are beneficial in RRMS.
Supported By: Serono International SA.
Category - MS and Related Diseases
SubCategory - Therapeutic Trials