SAN DIEGO—At 21 years, treatment with interferon beta-1b reduced the risk of death by approximately 47%, compared with placebo, for patients with multiple sclerosis (MS). Presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis, the data reflect the longest period of follow-up for a treatment-exposed MS population.
A Multicenter Observational Study
Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center, and colleagues conducted a multicenter observational study to evaluate the effects of interferon beta-1b on the clinical outcomes of patients with MS 21 years after the initiation of randomized treatment.
All patients enrolled in the 1988 pivotal randomized controlled trial of interferon beta-1b were eligible. In this trial, 125 patients received 50 µg of interferon beta-1b, 124 patients received 250 µg of interferon beta-1b, and 123 received placebo, every other day. Patients remained on randomized treatment for as long as 5.1 years, after which use of disease-modifying therapies was open label and at their own and their physicians’ discretion.
At the beginning of the trial, all patients were treatment naïve and between the ages of 18 and 50. Eligible patients’ Expanded Disability Status Scale score was 5.5 or less, and patients had had at least two clinical exacerbations during the previous two years.
A High Rate of Ascertainment
Approximately 21 years after enrollment in the initial trial, investigators identified 366 of the original 372 patients for follow-up. A total of 81 of the identified patients had died, including 37 patients randomized to placebo, 22 patients randomized to 50 µg of interferon beta-1b, and 22 patients randomized to 250 µg of interferon beta-1b. Compared with placebo, patients randomized to 250 µg of interferon beta-1b had a 46.8% reduction in the hazard rate of dying. Patients randomized to 50 µg of interferon beta-1b had a 46% lower hazard rate of dying than patients randomized to placebo.
An adjudication committee determined the relationship between MS and death in 69 of the 81 deaths. Approximately 78% of adjudicated deaths were considered to be MS-related. The excess deaths observed in the placebo group were largely explained by MS-related causes. Pulmonary infections secondary to MS were the most common cause of death.
The instances of cancer, heart attacks, and all other medical conditions that caused death were similar among patients receiving interferon beta-1b and patients receiving placebo, Dr. Reder told Neurology Reviews. Disability outcomes also were similar between groups.
In other trials, missing patients could affect the analysis. “Trials with information on less than 90% of the patients could miss important information on number of deaths and causes of death,” but this study achieved a 98% rate of ascertainment, Dr. Reder added.
Overall, 60% of patients stopped working because of MS. Nearly 31% of patients randomized to placebo accumulated enough disability to prevent them from maintaining employment, compared with 23% of patients randomized to 250 µg of interferon beta-1b and 32.7% of patients randomized to 50 µg of interferon beta-1b. A subset of 93 patients underwent cognitive assessment. Approximately 46% of patients showed no cognitive impairment, but nearly 29% of patients were cognitively impaired.
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