No Difference in MS Disease Activity Between Treatments 16 June 2007
Head-to-head comparison of interferon beta-1b (Betaseron, Bayer HealthCare Pharmaceuticals [erstwhile Berlex]) and glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) shows comparable efficacy but continuing multiple sclerosis (MS) disease activity with both agents.
The study, called Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints (BECOME), is the first investigator-initiated, randomised, prospective, rater-blinded trial to directly compare these 2 agents in the treatment of MS. The study was supported in part by a grant from Berlex/Schering AG.
Diego Cadavid, MD, associate professor in the department of neurology and neurosciences, New Jersey Medical School, in Newark, and the Multiple Sclerosis Center at Holy Name Hospital, in Teaneck, New Jersey, reported the findings here during the Whitaker Research Track presentations of the Consortium of Multiple Sclerosis Centers 21st Annual Meeting.
Seventy-five patients with MS were randomly assigned to treatment groups: 36 with interferon beta-1b and 39 with glatiramer acetate. Combined active lesions (CAL) were monitored monthly for 2 years using 3-tesla MRI with triple-dose gadolinium and a 40-minute delay to maximise enhancement. Clinical indications of relapse, cognition, and disability were also monitored. A total of 2754 CALs were identified during the study.
After 15 months of treatment, a similar number of lesions occurred in both treatment groups, but the occurrence of lesions varied considerably between patients. "Approximately half the MRIs in each group showed new lesions and half did not," he said.
Dr. Cadavid then reclassified the 75 patients by CAL pattern: no CALs for 2 years (n=15), episodic CALs (n=44), and frequent CALs (n=16). The occurrence of these patterns in the 2 treatment groups was not significantly different (Χ2, P = .7).
Disease activity continued to some extent in 77% to 83% of the patients, again with no significant difference between the 2 drug therapies.
Michael Racke, MD, chair of the department of neurology of Ohio State University and moderator of this session, focused his comments to Medscape on the unusually sensitive MRI technique. "In terms of clinical applicability, nobody's going to do monthly triple-dose gadolinium 3-tesla MRI. But the real problem is, we don't have a histologic correlate."
"Dr. Cadavid's data do suggest that the 2 drugs compared are very similar," continued Dr. Racke. However, he thinks the unusual MRI technique used in this study is measuring something different than an MRI with, for instance, a 1.5-tesla magnet after single-dose gadolinium. "Basically, since Berlex funded the study, they thought that Betaseron would beat Copaxone — and it didn't. So the issue becomes: Why is that? With a typical MRI, would you have seen what was anticipated? This technique is very sensitive, but we don't know exactly what we're measuring with that increased sensitivity."
Dr. Cadavid also analysed the results of the behavioural and cognitive tests for the 3 CAL pattern groups, including the 25-foot walk test, a test of response speed, and the cognitive skills index (CSI). In nearly every test, the group with frequent CALs scored lower than other groups in baseline testing and continued to do more poorly throughout the study.
Talking with Medscape, Dr. Cadavid said he had been very surprised to find that patients in the frequent-CAL group scored more poorly from the beginning of the assessments. As to why their impairment had not been noticed earlier, he commented: "It's a matter of how the relapse presents. If they lost vision in 1 eye, they'd be picked up right away. But if they have a subtle problem with balance, gait, or cognition, they may not be picked up. People tend to assign the symptoms to something else."
Regarding clinical utility of the 3 CAL patterns, Dr. Cadavid emphasised: "You cannot assume that just because you put [patients] on therapy you've got them under control. You have to be careful, especially with the group with frequent lesions, because they seem to already carry some loss of function when you first see them." Based on the results of this study, he added, "Even though you put them on the drug, you are not really controlling them. They're getting disabled in front of you."
The point is, he added, "after 10 or 12 years of these first-level drugs, we are entering a phase of what seem to be more powerful drugs with more serious side effects. We cannot put everybody in the same basket. It's time to become more selective and target the patients with more frequent lesions with what may be more powerful drugs with a higher risk."
Source: Consortium of Multiple Sclerosis Centers 21st Annual Meeting. John Whitaker Research Track. (16/06/07)
This one actually is an intelligent and informative review of where we are with the interferons and how we got here, which isn't doing the article justice but it's the best I can do. http://tinyurl.com/38xtse
I still have fundamental questions about whether the CRABS really work at all, and head to head studies basically show they (at least the two tested) have equally limited effectiveness for the group as a whole.
The big unexplored question is the groups in each category that DIDN"T show CALS for two years. Since we don't have a control, we don't know if the number of inactives was any higher in the treated groups than the controls. Trying to positive, let's assume that there is some effect of treatment based on past studies. Is there some characteristic of these people that is different from the others? Is there some biomarker that would differentiate the subset that might benefit from the treatment, either Copaxone or IF from those that don't benefit? That is the most useful question to answer in my mind, not whether one is better than the other for a random selection of MS patients. The emphasis in MS treatment seems to be on finding a one size fits all treatment, for a condition that actually may be different diseases to begin with.
I wish MS research would look to what is going on in the cancer research side. Using breast cancer as an example, depending on the cell type, whether it is estrogen sensitive or not, etc., dictates whether a given treatment will have effectiveness. There is no one size fits all treatment and the selection of the treatment is based on examination of the tumor cells, not on a pot shot, "try this and see if it works for you" approach, which is really what we have for MS. If there was some objective way of identifying responders from nonresponders, that would be an enormous step forward, especially for those responders. For the nonresponders, at least it would save the pain and expense of administering an ineffective drug. In the absence of any new meds, that would at least be something, and along the way more would be learned about MS. All these studies show a subgroup that seems to respond to treatment, and one that doesn't. The CRAB research should study THAT, not "which CRAB is better for everybody."
I participated in this study. You had to be newly diagnosed and had never been on any medications for ms before.
* I don't suffer from insanity, I enjoy it!
About the only sure thing with the CRABs over the years is they have brought in a ton of revenue to the companies that produce them!!I still have fundamental questions about whether the CRABS really work at all, and head to head studies basically show they (at least the two tested) have equally limited effectiveness for the group as a whole.
I have an opinion as to why Bayer (Berlex) funded this trial.....Betaseron's market share has been slipping and they needed something to show that they were better than Copaxone. Unfortunately they appear to have spent a ton of money and not obtained the results they needed for their marketing people. What other possible reason would a company spend that kind of money on a drug that had been around over 15 years?
One disturbing number that came out of this study...about 80% of the patients suffered disease progression while on either of the drugs Not my idea of a decent efficacy!