Independent Study of Over 1000 Enrolled Patients Shows Once Weekly Interferon Beta-1a as Effective as Every Other Day Interferon Beta-1b with Fewer Side Effects
Neurologists utilize the latest evidence-based medicine (EBM) presented at worldwide neurology meetings to make treatment decisions for their patients. Reliance upon randomized, well-controlled, and blinded clinical studies to validate the latest evidence-based data is paramount when understanding results and conclusions reached by investigators. However, not all studies are designed in this manner and therefore, should require closer scrutiny. Data presented at the ECTRIMS 2001 meeting in Dublin, Ireland provides further evidence to support the current standards of treatment for Multiple Sclerosis (MS). This report will review the latest evidence-based data and assist the neurologist in understanding the comparisons between MS treatments.
Two Year Comparative Study Confirms Once Weekly Interferon Beta-1a in Reducing MS Relapses
Predictors of Efficacy of Interferon Beta Treatment in Relapsing-Remitting Multiple Sclerosis (RRMS): Results From a Post-Marketing Surveillance Study.
Maria Trojano, MD, Department of Neurological and Psychiatric Services, University of Bari, Bari, Italy.
At the recent ECTRIMS 2001 meeting held in Dublin, Ireland in September, results from an independent study monitoring the efficacy, tolerability, and safety of interferon beta-1a (Avonex) and interferon beta-1b (Betaseron- US, Betaferon-Outside US) for the treatment of relapsing-remitting MS (RRMS) as administered in standard clinical practice1 were presented by Maria Trojano, MD, Director of the MS Center, Department of Neurological and Psychiatric Services, University of Bari, Bari, Italy. Additional study objectives included identification of baseline disease factors predictive of the clinical response to interferon beta treatment and comparison of the safety, tolerability, and efficacy of Avonex and Betaseron treatments in two RRMS groups who had completed a treatment period of 2 years.
The potential study participants were identified through a network of 16 specialized MS Centers throughout southern Italy. The study enrolled 1,033 patients with RRMS of which 408 patients completed 2 years of treatment with either Avonex (n = 177) or Betaseron (n = 231). Patients were prospectively monitored every three months for the entire 2-year treatment period. Demographic and clinical parameters at baseline being evaluated at 24 months follow-up included age at onset of interferon treatment, age at MS onset, disease duration, Expanded Disability Status Scale (EDSS) scores, and pre-treatment relapse rates.
Both interferon beta treatments demonstrated equivalent efficacy. Both treatment groups had significant reductions [p < 0.0001) in relapse rates at all time points [3, 6, 9, 12, 15, 18, 21 and 24 months] compared with baseline. Avonex dosed once weekly-reduced relapses by 65% compared to 59% in the Betaseron group dosed every 48 hours. “The present data suggest that long-term duration studies are needed to provide an accurate assessment of the effect of treatment on relapses in MS,” noted Dr. Trojano.
There were no differences between mean relapse rates or mean EDSS scores from baseline to year 2. However, EDSS scores in patients treated with Betaseron showed a significant increase (p < 0.05) from baseline over the 2-year treatment period, whereas no significant change in EDSS scores were seen in Avonex treated patients. Since physical disability assessment using the EDSS scale is currently considered the most useful clinical measure of MS disease activity, these results underscore Avonex’s ability to provide clinical stabilization by delaying progression of patient disability; Avonex may favorably impact on quality of life issues where it’s ability to delay progression of disability has been previously established.2
The study identified three clinical features predictive of response to interferon beta treatment: age at treatment onset, pretreatment relapse rate, and disease duration. Dr. Trojano said that the significant positive correlation between age of onset of interferon beta treatment and change from baseline in relapse rate [p < 0.01] and EDSS [p < 0.01] score was of particular interest, suggesting “that the earlier treatment is initiated with disease-modifying therapies, the better patients respond to therapy.”
The adverse event profiles for each interferon beta in the present study are similar to those reported in their respective pivotal Phase III studies.3,4 No new adverse events were identified. A lower incidence of adverse events during treatment initiation and fewer treatment discontinuations were observed in patients treated with Avonex [9%] compared with Betaseron [19%].
In general, higher incidences in both clinical and hematologic events were observed in patients treated with Betaseron compared with Avonex treated patients, particularly in the first three months of treatment. Adverse events included, fever (70% vs. 50%, p < 0.05), depression (14% vs. 6%, p < 0.0001 vs. subsequent post-treatment time points), leukopenia (22% vs. 6%, p < 0.05), anemia (18% vs. 5%, p < 0.05), and thrombocytopenia (4% vs. 1%). (Table 1)
Table1. Incidence of Adverse Events at 2 years