BEYOND and PRECISE Results Suggest Equivalence for Multiple Sclerosis Treatments By : Susan Jeffrey
April 17, 2008 (Chicago) — Final results of the largest multiple sclerosis (MS) trial to date suggest that, in terms of clinical effects, treatment with both 250- and 500-µg doses of interferon beta-1b (Betaferon/Betaseron, Bayer Healthcare Pharmaceuticals) as well as glatiramer acetate ( Copaxone, Teva Pharmaceutical Industries) were essentially equivalent in the risk of relapse in patients with relapsing-remitting MS.
Although there was some indication of reduced T2-lesion volume and number with interferon beta-1b, the researchers note, the long-term significance of this difference is unclear.
In a separate presentation, researchers reported full results of a randomized trial of glatiramer acetate vs placebo to prevent conversion to clinically definite MS in patients with clinically isolated syndromes (CIS). They report that fewer patients converted to clinically definite MS with treatment and those who did took longer to do so.
The full results of these studies, the Betaferon/Betaseron Efficacy Yielding Outcomes of a New Dose (BEYOND) and PRECISE trials, were presented here at the American Academy of Neurology 60th Annual Meeting. Top-line results from the studies, both company-sponsored trials, were previously announced by the companies in October and December of 2007, respectively.
The BEYOND trial compared the efficacy of 2 doses of interferon beta-1b, 250 and 500 µg, given subcutaneously every other day, with glatiramer acetate in patients with relapsing-remitting MS. This trial was funded by Bayer Schering Pharma AG, Berlin, Germany.
"The hypothesis was that the double dose of Betaseron would be more efficacious than the single dose, 500 µg better than 250 µg, in terms of efficacy, with comparable safety and tolerability," Paul O'Connor, MD, from the University of Toronto and St. Michael's Hospital, in Ontario, told Medscape Neurology & Neurosurgery. The 250-µg dose is currently approved in this indication.
A secondary hypothesis was to compare interferon beta-1b in these 2 doses with glatiramer acetate in terms of efficacy, safety, and tolerability, he said.
Patients eligible for the trial were relapsing-remitting MS patients with Expanded Disability Status Scale (EDSS) scores of 5.0 or less and 1 or more relapses in the year prior to study entry; all were treatment naive. A total of 2244 patients were randomized in a 2:2:1 ratio to the 500-µg dose (n=899), to the 250-µg dose (n=899), or to glatiramer acetate in a dose of 20 mg daily (n=448), also given subcutaneously for > 104 weeks. The average time of follow-up in the trial was about 2.3 years, Dr. O'Connor noted. Patients were evaluated clinically every 3 months and received a magnetic resonance imaging (MRI) scan every 12 months.
The primary end point was relapse risk. Results for this end point, he said, "showed that the performance of all 3 drugs was the same in terms of recurrent relapses, whether you did an intent-to-treat analysis or a per-protocol analysis."
The annualized relapse rate (ARR), a supportive end point, fell by almost 80% compared with the year prior to study entry, but without any intergroup differences, the authors note.
Other secondary end points, including time to confirmed disability and progression or change in "black-hole" volume on MRI, again showed no differences between groups, Dr. O'Connor added.
Some MRI end points did show differences favoring the interferon beta-1b treatment, he noted. The cumulative number of T2 lesions up to the last scan was greater with glatiramer acetate than with either the 500-µg dose ( P = .001) or the 250-µg dose ( P = .017) of interferon beta-1b. The relative increase in T2-lesion volume was also larger in patients on glatiramer acetate than in the 500-µg ( P = .001) or the 250-µg groups ( P < .001).
However, the authors write, the longer-term significance of these changes, "if any," is "unclear."
Dropout rates were highest in the high-dose interferon beta-1b group, at 19%; lowest with the lower dose, at 13%; and intermediate, at 17%, with glatiramer acetate. Adverse events were similar to the known profiles of these drugs — notably, flulike symptoms were more common with interferon beta-1b, and injection-site reactions including pain and pruritus were more common with glatiramer acetate.
Beyond the minor MRI differences and slightly different profile of adverse events, Dr. O'Connor noted, "the major message is really the similarity in behavior on efficacy measures of the 2 drugs.
"What this does is that it allows the patient and the doctor to decide more on the basis of items such as how often do you want to get injected or what matters more to you, a flu-like symptom vs some soreness where you were injected?" he concluded. "In other words, you can choose on the basis of adverse events as differentiating features."