S Flechter1, J Vardi, L Pollak, J M Rabey. 1. The MS Clinical Research and Therapy Service, Department of Neurology, Assaf Harofeh Medical Center,, Zerifin 70300 Israel.
Abstract
OBJECTIVE: To compare the clinical efficacy, as expressed by relapse rate and disability accumulation, and safety profile of glatiramer acetate (Copaxone; COP-1) and Interferon beta-1b (Betaferon; IFN beta - 1b) administered to multiple sclerosis patients during a 2-year follow-up on an open-label parallel design, as compared to their clinical condition in the 2-year period prior to treatment. BACKGROUND:Copaxone and IFN beta - 1b have been recently introduced for the treatment of relapsing forms of MS. Both medications have been proven to have a relatively safe profile and are used extensively world-wide. METHODS:58 consecutive patients with relapsing forms of MS were enrolled from the MS out-patient clinic, during three months. After being informed in detail of the two approved treatment options existing at the time in Israel, the patients chose by themselves to receive either: (a) Copaxone 20 mg subcutaneously (sc) daily (Copaxone dly, 20 patients), or (b) Copaxone 20 mg sc alternate-day (Copaxone alt, 18 patients) or (c) IFN beta-1b 8 MIU sc in alternate day (20 patients). Mean relapse rate/year and mean EDSS/year were calculated for each group of patients during the 2 years prior to the onset of treatment, and during the year prior to the onset of treatment. Statistical significance was observed in the relapse rate in the year prior to the onset of treatment between the IFN beta -1b group and the two Copaxone groups (p = 0.05). This statistical difference has no effect on the overall data of the 2 years prior to starting the treatment and on the results. No statistical significance was observed in the total number of relapses, and on the 2-year relapse rate, prior to the onset of treatment. Mean relapse rate/year and mean EDSS/year were calculated for each group during the first and second year of treatment. Wilcoxon analysis for clinical data and chi-square for adverse events were applied. RESULTS: The three groups were statistically comparable concerning mean relapse/year in the 2 years before the trial started and no statistical significance was observed among the three groups. A statistically significant reduction in the mean relapse rate in the 2 years after onset of treatment was observed in the three group of patients: Copaxone daily (dly) 1.1 +/- 0.6 (p = 0.0001); Copaxone alternate (alt) 0.9 +/- 0.6 (p = 0.0004) and IFN beta -1b 1.2 +/- 0.7 (p = 0.0001). Disability as expressed by EDSS score prior to the onset of treatment and after 2 years of treatment showed deterioration in the three groups although more significant in the Copaxone groups: Copaxone dly 3.3 +/- 1.4 to 3.8 +/- 1.6 (p = 0.007); Copaxone alt 2.4 +/- 1.1 to 2.8 +/- 1.3 (p=0.04); IFN beta - 1b 3.1 +/- 1.3 to 3.3 +/- 2.0 (N.S.). The most common adverse events reported were: (1) flu-like symptoms 7 pts (35%) in the IFN beta -1b group; 10 pts (26%) of the two Copaxone groups; (2) increased spasticity of lower limbs 3 pts (15%), only in the IFN beta -1b group; (3) site injection reaction (SIR): 16 SIR (80%) in the IFN beta -1b group; 12 SIR (67%) in the Copaxone alt group; 14 SIR (70%) in the Copaxone dly group; and (4) systemic reaction 3 pts (15%) in the IFN beta -1b group; 4 pts (22%) in the Copaxone alt group; 6 pts (30%) in the Copaxone dly group. Premature termination occurred in five patients treated with Copaxone (3 in the alternate group and 2 in the daily group). CONCLUSION: The present study, despite the limitations of an open-label study, shows that Copaxone dly, Copaxone alt and IFN beta -1b treatment seem to be equally effective for the control of exacerbations in MS. The adverse event profile, as reported by the patients, was also similar. However, the adverse events profile registered indicated that Copaxone is somewhat less detrimental, whereas disability as measured by EDSS accumulation showed that the interferon beta - 1b patients demonstrated a slower progression of the disability.
RCT Entities:
OBJECTIVE: To compare the clinical efficacy, as expressed by relapse rate and disability accumulation, and safety profile of glatiramer acetate (Copaxone; COP-1) and Interferon beta-1b (Betaferon; IFN beta - 1b) administered to multiple sclerosispatients during a 2-year follow-up on an open-label parallel design, as compared to their clinical condition in the 2-year period prior to treatment. BACKGROUND:Copaxone and IFN beta - 1b have been recently introduced for the treatment of relapsing forms of MS. Both medications have been proven to have a relatively safe profile and are used extensively world-wide. METHODS: 58 consecutive patients with relapsing forms of MS were enrolled from the MS out-patient clinic, during three months. After being informed in detail of the two approved treatment options existing at the time in Israel, the patients chose by themselves to receive either: (a) Copaxone 20 mg subcutaneously (sc) daily (Copaxone dly, 20 patients), or (b) Copaxone 20 mg sc alternate-day (Copaxone alt, 18 patients) or (c) IFN beta-1b 8 MIU sc in alternate day (20 patients). Mean relapse rate/year and mean EDSS/year were calculated for each group of patients during the 2 years prior to the onset of treatment, and during the year prior to the onset of treatment. Statistical significance was observed in the relapse rate in the year prior to the onset of treatment between the IFN beta -1b group and the two Copaxone groups (p = 0.05). This statistical difference has no effect on the overall data of the 2 years prior to starting the treatment and on the results. No statistical significance was observed in the total number of relapses, and on the 2-year relapse rate, prior to the onset of treatment. Mean relapse rate/year and mean EDSS/year were calculated for each group during the first and second year of treatment. Wilcoxon analysis for clinical data and chi-square for adverse events were applied. RESULTS: The three groups were statistically comparable concerning mean relapse/year in the 2 years before the trial started and no statistical significance was observed among the three groups. A statistically significant reduction in the mean relapse rate in the 2 years after onset of treatment was observed in the three group of patients: Copaxone daily (dly) 1.1 +/- 0.6 (p = 0.0001); Copaxone alternate (alt) 0.9 +/- 0.6 (p = 0.0004) and IFN beta -1b 1.2 +/- 0.7 (p = 0.0001). Disability as expressed by EDSS score prior to the onset of treatment and after 2 years of treatment showed deterioration in the three groups although more significant in the Copaxone groups: Copaxone dly 3.3 +/- 1.4 to 3.8 +/- 1.6 (p = 0.007); Copaxone alt 2.4 +/- 1.1 to 2.8 +/- 1.3 (p=0.04); IFN beta - 1b 3.1 +/- 1.3 to 3.3 +/- 2.0 (N.S.). The most common adverse events reported were: (1) flu-like symptoms 7 pts (35%) in the IFN beta -1b group; 10 pts (26%) of the two Copaxone groups; (2) increased spasticity of lower limbs 3 pts (15%), only in the IFN beta -1b group; (3) site injection reaction (SIR): 16 SIR (80%) in the IFN beta -1b group; 12 SIR (67%) in the Copaxone alt group; 14 SIR (70%) in the Copaxone dly group; and (4) systemic reaction 3 pts (15%) in the IFN beta -1b group; 4 pts (22%) in the Copaxone alt group; 6 pts (30%) in the Copaxone dly group. Premature termination occurred in five patients treated with Copaxone (3 in the alternate group and 2 in the daily group). CONCLUSION: The present study, despite the limitations of an open-label study, shows that Copaxone dly, Copaxone alt and IFN beta -1b treatment seem to be equally effective for the control of exacerbations in MS. The adverse event profile, as reported by the patients, was also similar. However, the adverse events profile registered indicated that Copaxone is somewhat less detrimental, whereas disability as measured by EDSS accumulation showed that the interferon beta - 1b patients demonstrated a slower progression of the disability.