Early treatment with interferon-beta in patients who have experienced a clinical event suggestive of multiple sclerosis can delay disability progression, said Dr. Ludwig Kappos of University Hospital, Basel (Switzerland).
The study, conducted in several European countries, was the follow-up of the initial phase of the BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) study of 468 people (mean age 30 years) with a first event suggestive of MS and at least two clinically silent MRI lesions. In the first 2-year phase of the study, 292 patients were randomized to start treatment with interferon beta-1b (250 mcg subcutaneously every other day) within 60 days of developing the event, and 176 received placebo. The follow-up study analyzed patients 3 years after the beginning of the 2-year placebo-controlled phase and enrolled nearly 90%—418—of the patients who had completed that phase; 378 chose to take interferon-beta starting at 2 years, and 392 completed the 3-year follow-up. At that time, 16% of patients in the early-treatment group had confirmed progression on the Expanded Disability Status Scale (EDSS), versus 24% of patients in the delayed treatment group. Treatment was tied to a 40% reduced risk. The number needed to treat early to avoid one additional confirmed case of EDSS progression was almost 12, the authors wrote (Lancet 2007;370:389–97).
Also at 3 years, 37% of patients in the early-therapy group developed conversion to clinically definite MS (CDMS) vs. 51% of those who received delayed treatment, a 41% risk reduction. The number needed to treat early to avoid one additional CDMS conversion was seven. Over the 3 years, patient-reported functional assessment scale scores were high and stable.
The early-treatment group was exposed to interferon-beta for a median of 1,080 days over 3 years, versus a median of 364 days in the delayed treatment group.
The impact on the EDSS 3 years after the onset of the first MS-type event indicates that “a delay of such treatment by, essentially, just one event, even at this early stage of the disease, has an effect on later accumulation of disability,” Dr. Kappos and his associates wrote.
Adverse events were typical of the side effect profile; flulike symptoms and injection site reactions were reported in about half of all patients.
The authors noted that in three multicenter, placebo-controlled studies, CDMS was delayed in patients who received treatment with interferon-beta for a first episode of neurologic symptoms that were highly suggestive of MS. But to date, they said, there had been no controlled evidence that early initiation of treatment with interferon-beta affects the development of confirmed disability, compared with delaying treatment. A 5-year follow-up of the participants is planned.
In an accompanying editorial, Dr. Sean J. Pittock of the departments of neurology and laboratory medicine and pathology at the Mayo Clinic, Rochester, Minn., said that though the study presents the first evidence of interferon beta-1b's benefit, the magnitude of benefit, though statistically significant, is clinically small (Lancet 2007;370:363–4).
Interferon beta-1b is marketed in the U.S. by Bayer HealthCare Pharmaceuticals Inc. as Betaseron, with approval for treating relapsing forms of MS to reduce the frequency of clinical exacerbations. The approved label includes the statement that patients with MS “in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with” MS.
Dr. Pittock disclosed no conflict of interest. Some of the study's authors were from Bayer Schering Pharma AG. The disclosure statement for the other authors, including Dr. Kappos, listed several as having received research support and having served as consultants to Bayer Schering and other pharmaceutical companies.