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SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
SAN DIEGO – Baseline Expanded Disability Status Scale scores and number of relapses during the first year were the most consistent predictors of disability worsening or relapses over the subsequent 3 years in long-term analysis of three phase 3 fingolimod trials.
Those patients identified at higher risk for worse long-term clinical outcomes could benefit from an early review of multiple sclerosis (MS) treatment regimens to help prevent worsening disability, Pavle Repovic, MD, PhD, said in an interview.
“The idea for some time now has been to figure out what will tell whether a patient is responding to a therapy early on or not,” Dr. Repovic said at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To explore long-term clinical predictors of disability progression and relapse risk, Dr. Repovic and his colleagues analyzed three phase 3 trials assessing fingolimod (Gilenya). They evaluated parameters at baseline and during the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.
Investigators in the FREEDOMS studies enrolled 1,118 people with relapsing MS and randomized them to fingolimod or placebo for 2 years. The patients who were initially treated with placebo were then re-randomized to one of two fingolimod doses for an additional 18 months. Finally, all participants underwent treatment with the same fingolimod dose during an open-label phase. Similarly, in TRANSFORMS, researchers enrolled 1,292 people with relapsing MS and randomized them to either fingolimod or interferon beta-1a for 1 year. They then re-randomized the interferon beta-1a group to one of two fingolimod doses for a 1-year extension, then assigned all participants to one dose of fingolimod for an open-label phase.
At baseline in the FREEDOMS and FREEDOMS II studies, a longer duration of MS was associated with a higher risk for clinically definite progression or relapses at 6 months (odds ratio, 1.040), as was baseline Expanded Disability Status Scale (EDSS) score (OR, 1.229).
“In the FREEDOMS trials, what we learned is that the duration of multiple sclerosis since diagnosis and the baseline disability predict worsening between 1 and 4 years,” said Dr. Repovic, a neurologist with the Multiple Sclerosis Center at the Swedish Neuroscience Institute in Seattle.
Dr. Repovic added that “there is nothing you can do about them [the baseline predictors]. Patients are as disabled as they are, and they’ve had multiple sclerosis as long as they have.”
The researchers also looked at predictors of 6-month confirmed disability progression or relapses during the first year. “The idea is that year 1 might tell you what happens next,” Dr. Repovic said. The number of confirmed relapses (OR, 2.788) and MRI lesion activity (OR, 1.638), were predictive.
“So breakthrough disease in year 1 predicts more disease down the road.”
In the TRANSFORMS trial, previous treatment for MS (OR, 1.613) and EDSS score at baseline (OR, 1.228) predicted who would do worse. The number of confirmed relapses in the first year of the study was the only predictor (OR, 1.774). There was a trend for MRI lesion activity that approached statistical significance.
The confirmed number of relapses in the first year was the common predictor among all the phase 3 studies. “So with people who relapse, we really need to watch out for them,” Dr. Repovic said.
“The challenge with this particular study is we took everybody,” Dr. Repovic added. Next he would like to look at only those participants who received fingolimod throughout the trials to see if any specific predictors emerge.
Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
SOURCE: Repovic P et al. Abstract P210.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Certain factors at baseline and over first year of three pooled studies were associated with worse long-term multiple sclerosis outcomes.
Major finding: The number of confirmed relapses in the first year of the FREEDOMS, FREEDOMS II, and TRANSFORMS studies predicted worse subsequent outcomes.
Study details: Pooled data from three phase 3 trials of fingolimod with 2,355 patients.
Disclosures: Dr. Repovic disclosed he is on the speakers bureau for Novartis, the company that sponsored the study.
Source: Repovic P et al. Abstract P210.