Two MS Drug Studies Yield Divergent Clinical Findings

ATLANTA—A pair of studies directly comparing the effectiveness of interferon beta and glatiramer acetate for patients with multiple sclerosis (MS) have found contrasting results, which are dependent on the clinical criteria that are being measured.

In one study, interferon beta-1b was more effective than glatiramer acetate in limiting the conversion of newly enhancing lesions and acute black holes to chronic black holes, which are thought to represent irreversible damage in MS, reported Stuart D. Cook, MD, and colleagues in the August 16 online Journal of Neurology, Neurosurgery, and Psychiatry. However, the two-year risk of relapse was significantly lower in patients with MS who used glatiramer acetate than among those who used interferon beta-lb, interferon beta-1a IM, and interferon beta-1a SC, reported Kenneth P. Johnson, MD, and colleagues at the 2009 Joint Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Chronic Black Holes in MS
Dr. Cook’s group followed 75 patients with relapsing-remitting MS or a clinically isolated syndrome in the ongoing prospective, randomized Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints (BECOME) study. The researchers used monthly 3-Tesla brain MRI scans for up to two years to observe the development and evolution of new black holes in the participants, who were randomized to receive glatiramer acetate or interferon beta-1b.

A total of 1,224 newly enhancing lesions appearing at baseline through 24 months were observed in 61 patients; 767 (62.7%) lesions showed an acute black hole. “The majority of acute black holes were transient and of similar duration by treatment group,” stated Dr. Cook, Professor of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School in Newark, and coauthors. “Black holes are more common in patients with secondary progression than with relapsing-remitting MS and in aggressive than in benign MS.”

Follow-up scans were available for one year or more regarding 571 acute black holes. The investigators found that 103 (18.8%) black holes were still visible 12 or more months after onset and were thus characterized as chronic black holes. About 12% of the 849 newly enhancing lesions with MRI follow-up for one or more years converted to chronic black holes—9.8% with interferon beta-1b and 15.2% with glatiramer acetate. In addition, the conversion rate from acute black holes to chronic black holes was also lower with interferon beta-1b (15.2%) than with glatiramer acetate (21.4%).

“Although we did find a significantly lower conversion rate from newly enhancing lesions to chronic black holes in brain lesions that develop in patients randomized to interferon beta-1b compared to glatiramer acetate, the difference was modest,” Dr. Cook and colleagues reported. “However, this was an unexpected finding because of the widespread belief in the MS field that glatiramer acetate, but not interferon beta-1b, is neuroprotective. The analysis of the primary outcome of BECOME showed no differences by treatment group in brain MRI activity over one year or in new brain lesion formation or annualized relapse rates over two years.

“Although our study of black holes supports the view that extensive repair takes place in the majority of new brain lesions that occur in relapsing-remitting MS patients treated with first-line disease modifying therapies, it remains to be determined whether similar repair takes place in normal appearing white and gray matter and why lesion repair appears to fail over time in many patients and even early on in some patients.”

Dr. Cook noted that patients with MS are usually started on an interferon beta or glatiramer acetate, but “all are effective drugs,” he told Neurology Reviews. “There are advantages and disadvantages of each drug. Patients and physicians need to discuss the options to select the best drug based on efficacy and tolerability. All are very safe.

“As yet, there is insufficient long-term clinical data to support choosing an interferon versus glatiramer acetate. Recent studies support possible MRI benefit of interferons—for example, the REGARD, BEYOND, and BECOME studies.”

Relapse Rates in MS
Dr. Johnson’s group identified 51,162 patients with MS from an administrative claims database. The investigators conducted a series of pair-wise comparisons between patients who used glatiramer acetate and those who used each of the three interferon beta drugs under usual care conditions in the trial, which was not randomized or prospective. Demographic profiles of participants among the four treatment groups were similar, and no differences regarding use of immunomodulators was observed among patients from various geographic regions. Relapse was defined as either hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

The researchers found that the two-year risk of relapse for patients who had received glatiramer acetate was 5.3%, compared with a rate of 13.5% in those who had received interferon beta-1b. The two-year risk of relapse for those who had taken glatiramer acetate was 5.2%, versus a rate of 10% among those who used interferon beta-1a IM. The two-year risk of relapse was 5.9% in those who had used glatiramer acetate, compared with 10.9% in those who had taken interferon beta-1a SC.

“In this recent comparison of immunomodulators for MS, the two-year risk of relapse was significantly lower for glatiramer acetate than for any of the three interferon beta drugs,” stated Dr. Johnson, Professor Emeritus of Neurology, University of Maryland, and Program Director of the Maryland Center for MS in Baltimore. “Nationwide outcomes came from treating physicians’ personal treatment decisions, free of drug company–sponsored studies or programs.”

In an interview with Neurology Reviews, Dr. Johnson said, “[Our] data show that in the broad population of patients across the US, glatiramer acetate works better than any of the interferons and is less costly, but it doesn’t work in every patient. We’re just now beginning to figure out which patients respond to which drugs.

“My recommendation,” advised Dr. Johnson, “is to start with glatiramer acetate, and if the patients do well, and probably around 60% of them will do well, then that’s the drug of choice. But for those patients who seem to respond poorly, we now have other choices.

“There are several problems with interferons that don’t occur with glatiramer acetate,” he continued. “Depending on the interferon, as many as a third of patients may develop neutralizing antibodies, in which case the drug is no longer effective. Rare patients develop liver toxicity and have to be taken off the interferon. So there are some indications for wanting to take patients off interferon. But if they’re doing well, there is no reason to do that. Interferons have been tested long enough [for clinicians] to know that they are effective but not as effective as glatiramer acetate, and they have more problems and more side effects.”

Dr. Johnson pointed out that it is important to differentiate between efficacy and effectiveness when interpreting his study’s results. Efficacy is the finding from a [specific] population of patients like we define in clinical trials, and in those situations the drugs were probably more or less equal,” he said. “However, in effectiveness, which is the broad category of patients in the US population with any disease, the effectiveness may not be the same as efficacy, and that’s why these findings are coming out the way they are.”

ATLANTA—A pair of studies directly comparing the effectiveness of interferon beta and glatiramer acetate for patients with multiple sclerosis (MS) have found contrasting results, which are dependent on the clinical criteria that are being measured.

In one study, interferon beta-1b was more effective than glatiramer acetate in limiting the conversion of newly enhancing lesions and acute black holes to chronic black holes, which are thought to represent irreversible damage in MS, reported Stuart D. Cook, MD, and colleagues in the August 16 online Journal of Neurology, Neurosurgery, and Psychiatry. However, the two-year risk of relapse was significantly lower in patients with MS who used glatiramer acetate than among those who used interferon beta-lb, interferon beta-1a IM, and interferon beta-1a SC, reported Kenneth P. Johnson, MD, and colleagues at the 2009 Joint Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Chronic Black Holes in MS
Dr. Cook’s group followed 75 patients with relapsing-remitting MS or a clinically isolated syndrome in the ongoing prospective, randomized Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints (BECOME) study. The researchers used monthly 3-Tesla brain MRI scans for up to two years to observe the development and evolution of new black holes in the participants, who were randomized to receive glatiramer acetate or interferon beta-1b.

A total of 1,224 newly enhancing lesions appearing at baseline through 24 months were observed in 61 patients; 767 (62.7%) lesions showed an acute black hole. “The majority of acute black holes were transient and of similar duration by treatment group,” stated Dr. Cook, Professor of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School in Newark, and coauthors. “Black holes are more common in patients with secondary progression than with relapsing-remitting MS and in aggressive than in benign MS.”

Follow-up scans were available for one year or more regarding 571 acute black holes. The investigators found that 103 (18.8%) black holes were still visible 12 or more months after onset and were thus characterized as chronic black holes. About 12% of the 849 newly enhancing lesions with MRI follow-up for one or more years converted to chronic black holes—9.8% with interferon beta-1b and 15.2% with glatiramer acetate. In addition, the conversion rate from acute black holes to chronic black holes was also lower with interferon beta-1b (15.2%) than with glatiramer acetate (21.4%).

“Although we did find a significantly lower conversion rate from newly enhancing lesions to chronic black holes in brain lesions that develop in patients randomized to interferon beta-1b compared to glatiramer acetate, the difference was modest,” Dr. Cook and colleagues reported. “However, this was an unexpected finding because of the widespread belief in the MS field that glatiramer acetate, but not interferon beta-1b, is neuroprotective. The analysis of the primary outcome of BECOME showed no differences by treatment group in brain MRI activity over one year or in new brain lesion formation or annualized relapse rates over two years.

“Although our study of black holes supports the view that extensive repair takes place in the majority of new brain lesions that occur in relapsing-remitting MS patients treated with first-line disease modifying therapies, it remains to be determined whether similar repair takes place in normal appearing white and gray matter and why lesion repair appears to fail over time in many patients and even early on in some patients.”

Dr. Cook noted that patients with MS are usually started on an interferon beta or glatiramer acetate, but “all are effective drugs,” he told Neurology Reviews. “There are advantages and disadvantages of each drug. Patients and physicians need to discuss the options to select the best drug based on efficacy and tolerability. All are very safe.

“As yet, there is insufficient long-term clinical data to support choosing an interferon versus glatiramer acetate. Recent studies support possible MRI benefit of interferons—for example, the REGARD, BEYOND, and BECOME studies.”

Relapse Rates in MS
Dr. Johnson’s group identified 51,162 patients with MS from an administrative claims database. The investigators conducted a series of pair-wise comparisons between patients who used glatiramer acetate and those who used each of the three interferon beta drugs under usual care conditions in the trial, which was not randomized or prospective. Demographic profiles of participants among the four treatment groups were similar, and no differences regarding use of immunomodulators was observed among patients from various geographic regions. Relapse was defined as either hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

The researchers found that the two-year risk of relapse for patients who had received glatiramer acetate was 5.3%, compared with a rate of 13.5% in those who had received interferon beta-1b. The two-year risk of relapse for those who had taken glatiramer acetate was 5.2%, versus a rate of 10% among those who used interferon beta-1a IM. The two-year risk of relapse was 5.9% in those who had used glatiramer acetate, compared with 10.9% in those who had taken interferon beta-1a SC.

“In this recent comparison of immunomodulators for MS, the two-year risk of relapse was significantly lower for glatiramer acetate than for any of the three interferon beta drugs,” stated Dr. Johnson, Professor Emeritus of Neurology, University of Maryland, and Program Director of the Maryland Center for MS in Baltimore. “Nationwide outcomes came from treating physicians’ personal treatment decisions, free of drug company–sponsored studies or programs.”

In an interview with Neurology Reviews, Dr. Johnson said, “[Our] data show that in the broad population of patients across the US, glatiramer acetate works better than any of the interferons and is less costly, but it doesn’t work in every patient. We’re just now beginning to figure out which patients respond to which drugs.

“My recommendation,” advised Dr. Johnson, “is to start with glatiramer acetate, and if the patients do well, and probably around 60% of them will do well, then that’s the drug of choice. But for those patients who seem to respond poorly, we now have other choices.

“There are several problems with interferons that don’t occur with glatiramer acetate,” he continued. “Depending on the interferon, as many as a third of patients may develop neutralizing antibodies, in which case the drug is no longer effective. Rare patients develop liver toxicity and have to be taken off the interferon. So there are some indications for wanting to take patients off interferon. But if they’re doing well, there is no reason to do that. Interferons have been tested long enough [for clinicians] to know that they are effective but not as effective as glatiramer acetate, and they have more problems and more side effects.”

Dr. Johnson pointed out that it is important to differentiate between efficacy and effectiveness when interpreting his study’s results. Efficacy is the finding from a [specific] population of patients like we define in clinical trials, and in those situations the drugs were probably more or less equal,” he said. “However, in effectiveness, which is the broad category of patients in the US population with any disease, the effectiveness may not be the same as efficacy, and that’s why these findings are coming out the way they are.”

ATLANTA—A pair of studies directly comparing the effectiveness of interferon beta and glatiramer acetate for patients with multiple sclerosis (MS) have found contrasting results, which are dependent on the clinical criteria that are being measured.

In one study, interferon beta-1b was more effective than glatiramer acetate in limiting the conversion of newly enhancing lesions and acute black holes to chronic black holes, which are thought to represent irreversible damage in MS, reported Stuart D. Cook, MD, and colleagues in the August 16 online Journal of Neurology, Neurosurgery, and Psychiatry. However, the two-year risk of relapse was significantly lower in patients with MS who used glatiramer acetate than among those who used interferon beta-lb, interferon beta-1a IM, and interferon beta-1a SC, reported Kenneth P. Johnson, MD, and colleagues at the 2009 Joint Meeting of the Consortium of MS Centers and Americas Committee for Treatment and Research in MS.

Chronic Black Holes in MS
Dr. Cook’s group followed 75 patients with relapsing-remitting MS or a clinically isolated syndrome in the ongoing prospective, randomized Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints (BECOME) study. The researchers used monthly 3-Tesla brain MRI scans for up to two years to observe the development and evolution of new black holes in the participants, who were randomized to receive glatiramer acetate or interferon beta-1b.

A total of 1,224 newly enhancing lesions appearing at baseline through 24 months were observed in 61 patients; 767 (62.7%) lesions showed an acute black hole. “The majority of acute black holes were transient and of similar duration by treatment group,” stated Dr. Cook, Professor of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School in Newark, and coauthors. “Black holes are more common in patients with secondary progression than with relapsing-remitting MS and in aggressive than in benign MS.”

Follow-up scans were available for one year or more regarding 571 acute black holes. The investigators found that 103 (18.8%) black holes were still visible 12 or more months after onset and were thus characterized as chronic black holes. About 12% of the 849 newly enhancing lesions with MRI follow-up for one or more years converted to chronic black holes—9.8% with interferon beta-1b and 15.2% with glatiramer acetate. In addition, the conversion rate from acute black holes to chronic black holes was also lower with interferon beta-1b (15.2%) than with glatiramer acetate (21.4%).

“Although we did find a significantly lower conversion rate from newly enhancing lesions to chronic black holes in brain lesions that develop in patients randomized to interferon beta-1b compared to glatiramer acetate, the difference was modest,” Dr. Cook and colleagues reported. “However, this was an unexpected finding because of the widespread belief in the MS field that glatiramer acetate, but not interferon beta-1b, is neuroprotective. The analysis of the primary outcome of BECOME showed no differences by treatment group in brain MRI activity over one year or in new brain lesion formation or annualized relapse rates over two years.

“Although our study of black holes supports the view that extensive repair takes place in the majority of new brain lesions that occur in relapsing-remitting MS patients treated with first-line disease modifying therapies, it remains to be determined whether similar repair takes place in normal appearing white and gray matter and why lesion repair appears to fail over time in many patients and even early on in some patients.”

Dr. Cook noted that patients with MS are usually started on an interferon beta or glatiramer acetate, but “all are effective drugs,” he told Neurology Reviews. “There are advantages and disadvantages of each drug. Patients and physicians need to discuss the options to select the best drug based on efficacy and tolerability. All are very safe.

“As yet, there is insufficient long-term clinical data to support choosing an interferon versus glatiramer acetate. Recent studies support possible MRI benefit of interferons—for example, the REGARD, BEYOND, and BECOME studies.”

Relapse Rates in MS
Dr. Johnson’s group identified 51,162 patients with MS from an administrative claims database. The investigators conducted a series of pair-wise comparisons between patients who used glatiramer acetate and those who used each of the three interferon beta drugs under usual care conditions in the trial, which was not randomized or prospective. Demographic profiles of participants among the four treatment groups were similar, and no differences regarding use of immunomodulators was observed among patients from various geographic regions. Relapse was defined as either hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

The researchers found that the two-year risk of relapse for patients who had received glatiramer acetate was 5.3%, compared with a rate of 13.5% in those who had received interferon beta-1b. The two-year risk of relapse for those who had taken glatiramer acetate was 5.2%, versus a rate of 10% among those who used interferon beta-1a IM. The two-year risk of relapse was 5.9% in those who had used glatiramer acetate, compared with 10.9% in those who had taken interferon beta-1a SC.

“In this recent comparison of immunomodulators for MS, the two-year risk of relapse was significantly lower for glatiramer acetate than for any of the three interferon beta drugs,” stated Dr. Johnson, Professor Emeritus of Neurology, University of Maryland, and Program Director of the Maryland Center for MS in Baltimore. “Nationwide outcomes came from treating physicians’ personal treatment decisions, free of drug company–sponsored studies or programs.”

In an interview with Neurology Reviews, Dr. Johnson said, “[Our] data show that in the broad population of patients across the US, glatiramer acetate works better than any of the interferons and is less costly, but it doesn’t work in every patient. We’re just now beginning to figure out which patients respond to which drugs.

“My recommendation,” advised Dr. Johnson, “is to start with glatiramer acetate, and if the patients do well, and probably around 60% of them will do well, then that’s the drug of choice. But for those patients who seem to respond poorly, we now have other choices.

“There are several problems with interferons that don’t occur with glatiramer acetate,” he continued. “Depending on the interferon, as many as a third of patients may develop neutralizing antibodies, in which case the drug is no longer effective. Rare patients develop liver toxicity and have to be taken off the interferon. So there are some indications for wanting to take patients off interferon. But if they’re doing well, there is no reason to do that. Interferons have been tested long enough [for clinicians] to know that they are effective but not as effective as glatiramer acetate, and they have more problems and more side effects.”

Dr. Johnson pointed out that it is important to differentiate between efficacy and effectiveness when interpreting his study’s results. Efficacy is the finding from a [specific] population of patients like we define in clinical trials, and in those situations the drugs were probably more or less equal,” he said. “However, in effectiveness, which is the broad category of patients in the US population with any disease, the effectiveness may not be the same as efficacy, and that’s why these findings are coming out the way they are.”