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Teriflunomide significantly reduced the annualized relapse rate in patients with relapsing-remitting multiple sclerosis by more than one-third, compared with placebo, in the second of two large, randomized, phase III trials that have been conducted with the drug.
The latest study, called TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis), demonstrated that the 14-mg dose of teriflunomide produced a 36% relative risk reduction in the annualized relapse rate, compared with placebo (P = .0001). A 7-mg dose of the oral MS agent yielded a 22% relative risk reduction (P = .0183).
Teriflunomide 14 mg, but not 7 mg, was also associated with a significantly lower sustained disability accumulation than placebo.
"These data support the use of teriflunomide as an initial therapy for patients with relapsing-remitting multiple sclerosis and as an option for patients who are unable to tolerate other disease-modifying therapies," wrote the TOWER Trial Group investigators (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(13)70308-9]).
First author Dr. Christian Confavreux of University Claude Bernard Lyon 1, France, and his associates commented that the findings add to those previously reported from the phase III TEMSO trial (N. Engl. J. Med. 2011;365:1293-303), which showed that teriflunomide 7 mg and 14 mg both reduced the annualized relapse rate by around 31% when compared with placebo. They are also supported by the results of a phase II extension study.
Teriflunomide was approved for the treatment of adults with relapsing-remitting MS in the United States (trade name Aubagio) in 2012 and in Europe in 2013. The drug is the principal active metabolite in leflunomide, which is licensed for the treatment of rheumatoid arthritis.
The TOWER trial involved a total of 1,169 patients with relapsing-remitting MS who were randomized to treatment: 408 were assigned to teriflunomide 14 mg, 372 to teriflunomide 7 mg, and 389 to placebo. The mean age of patients at study entry was approximately 38 years, with just over 80% being of white, 15% of Asian, and 2% of black ethnicity.
The annualized relapse rates were 0.50 for patients treated with placebo, 0.32 for patients treated with teriflunomide 14 mg, and 0.39 for those treated with teriflunomide 7 mg. Absolute risk reductions for teriflunomide 14 mg and 7 mg versus placebo were –0.11 and –0.18, respectively.
A key secondary endpoint was sustained accumulation of disability. This was defined as an increase of at least 1 point on the Expanded Disability Status Scale (EDSS) from baseline that persisted for at least 12 weeks. The hazard ratios for the time to sustained accumulation of disability were 0.68 (P = .0442) for the 14-mg dose of teriflunomide and 0.95 for the 7-mg dose versus placebo.
"The safety and tolerability profile of teriflunomide, as characterized in this and previous studies, was similar for both the 7-mg and 14-mg doses, including long-term treatment observations," the investigators wrote. The most common side effects seen in patients treated with teriflunomide were hair thinning, headache, and increase in alanine aminotransferase concentrations.
Genzyme, a Sanofi company, sponsored the trial. The investigators disclosed financial relationships with Genzyme as well as other companies that manufacture drugs used to treat MS.
The TOWER study findings appear to corroborate the results from the TEMSO trial, which formed the primary basis of teriflunomide’s approval in the United States and Europe.
One of the limitations of the TOWER study perhaps is the relatively high percentage of Asian participants, which raises concern over the generalizability of the results with studies that have been predominantly performed in North American or Western European populations. Additionally, patients were not all exposed to the same duration of treatment with teriflunomide. Rather than a standard 52 or 104 weeks of therapy, patients were treated until 48 weeks after the last patient was randomized into the study. This means that some patients might have been treated for much less or much longer than in other studies. It might provide the opportunity to do post hoc analyses, however, of the few patients that were exposed to treatment for longer.
They noted that it is somewhat surprising that 30% of patients did not complete the study while on study medication given that it is an oral, once-daily treatment, but that rate is in line with the TEMSO trial results and other studies of oral drugs for MS.
MS treatment has become increasingly complex over the years. Head-to-head trials with other oral immunotherapies and more established injectable drugs, such as interferon-beta and glatiramer acetate, are needed, however, to help patients and their physicians when selecting the best overall therapy. Global patient registries of all available treatments are also needed to obtain real-world data on their relative efficacy and safety and to inform clinical decision making.
Dr. Bernd C. Kieseier is professor of clinical and experimental neuroimmunology at Heinrich Heine University in Düsseldorf, Germany. Dr. Heinz Wiendl is professor of neurology and chair of the department of neurology at Westfälische Wilhelms University, Münster. They have received honoraria for lecturing, travel expense reimbursement, and research funding from companies involved in the manufacture of MS drugs. Their commentary is summarized from an editorial accompanying the TOWER trial report (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(14)70012-2]).
The TOWER study findings appear to corroborate the results from the TEMSO trial, which formed the primary basis of teriflunomide’s approval in the United States and Europe.
One of the limitations of the TOWER study perhaps is the relatively high percentage of Asian participants, which raises concern over the generalizability of the results with studies that have been predominantly performed in North American or Western European populations. Additionally, patients were not all exposed to the same duration of treatment with teriflunomide. Rather than a standard 52 or 104 weeks of therapy, patients were treated until 48 weeks after the last patient was randomized into the study. This means that some patients might have been treated for much less or much longer than in other studies. It might provide the opportunity to do post hoc analyses, however, of the few patients that were exposed to treatment for longer.
They noted that it is somewhat surprising that 30% of patients did not complete the study while on study medication given that it is an oral, once-daily treatment, but that rate is in line with the TEMSO trial results and other studies of oral drugs for MS.
MS treatment has become increasingly complex over the years. Head-to-head trials with other oral immunotherapies and more established injectable drugs, such as interferon-beta and glatiramer acetate, are needed, however, to help patients and their physicians when selecting the best overall therapy. Global patient registries of all available treatments are also needed to obtain real-world data on their relative efficacy and safety and to inform clinical decision making.
Dr. Bernd C. Kieseier is professor of clinical and experimental neuroimmunology at Heinrich Heine University in Düsseldorf, Germany. Dr. Heinz Wiendl is professor of neurology and chair of the department of neurology at Westfälische Wilhelms University, Münster. They have received honoraria for lecturing, travel expense reimbursement, and research funding from companies involved in the manufacture of MS drugs. Their commentary is summarized from an editorial accompanying the TOWER trial report (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(14)70012-2]).
The TOWER study findings appear to corroborate the results from the TEMSO trial, which formed the primary basis of teriflunomide’s approval in the United States and Europe.
One of the limitations of the TOWER study perhaps is the relatively high percentage of Asian participants, which raises concern over the generalizability of the results with studies that have been predominantly performed in North American or Western European populations. Additionally, patients were not all exposed to the same duration of treatment with teriflunomide. Rather than a standard 52 or 104 weeks of therapy, patients were treated until 48 weeks after the last patient was randomized into the study. This means that some patients might have been treated for much less or much longer than in other studies. It might provide the opportunity to do post hoc analyses, however, of the few patients that were exposed to treatment for longer.
They noted that it is somewhat surprising that 30% of patients did not complete the study while on study medication given that it is an oral, once-daily treatment, but that rate is in line with the TEMSO trial results and other studies of oral drugs for MS.
MS treatment has become increasingly complex over the years. Head-to-head trials with other oral immunotherapies and more established injectable drugs, such as interferon-beta and glatiramer acetate, are needed, however, to help patients and their physicians when selecting the best overall therapy. Global patient registries of all available treatments are also needed to obtain real-world data on their relative efficacy and safety and to inform clinical decision making.
Dr. Bernd C. Kieseier is professor of clinical and experimental neuroimmunology at Heinrich Heine University in Düsseldorf, Germany. Dr. Heinz Wiendl is professor of neurology and chair of the department of neurology at Westfälische Wilhelms University, Münster. They have received honoraria for lecturing, travel expense reimbursement, and research funding from companies involved in the manufacture of MS drugs. Their commentary is summarized from an editorial accompanying the TOWER trial report (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(14)70012-2]).
Teriflunomide significantly reduced the annualized relapse rate in patients with relapsing-remitting multiple sclerosis by more than one-third, compared with placebo, in the second of two large, randomized, phase III trials that have been conducted with the drug.
The latest study, called TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis), demonstrated that the 14-mg dose of teriflunomide produced a 36% relative risk reduction in the annualized relapse rate, compared with placebo (P = .0001). A 7-mg dose of the oral MS agent yielded a 22% relative risk reduction (P = .0183).
Teriflunomide 14 mg, but not 7 mg, was also associated with a significantly lower sustained disability accumulation than placebo.
"These data support the use of teriflunomide as an initial therapy for patients with relapsing-remitting multiple sclerosis and as an option for patients who are unable to tolerate other disease-modifying therapies," wrote the TOWER Trial Group investigators (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(13)70308-9]).
First author Dr. Christian Confavreux of University Claude Bernard Lyon 1, France, and his associates commented that the findings add to those previously reported from the phase III TEMSO trial (N. Engl. J. Med. 2011;365:1293-303), which showed that teriflunomide 7 mg and 14 mg both reduced the annualized relapse rate by around 31% when compared with placebo. They are also supported by the results of a phase II extension study.
Teriflunomide was approved for the treatment of adults with relapsing-remitting MS in the United States (trade name Aubagio) in 2012 and in Europe in 2013. The drug is the principal active metabolite in leflunomide, which is licensed for the treatment of rheumatoid arthritis.
The TOWER trial involved a total of 1,169 patients with relapsing-remitting MS who were randomized to treatment: 408 were assigned to teriflunomide 14 mg, 372 to teriflunomide 7 mg, and 389 to placebo. The mean age of patients at study entry was approximately 38 years, with just over 80% being of white, 15% of Asian, and 2% of black ethnicity.
The annualized relapse rates were 0.50 for patients treated with placebo, 0.32 for patients treated with teriflunomide 14 mg, and 0.39 for those treated with teriflunomide 7 mg. Absolute risk reductions for teriflunomide 14 mg and 7 mg versus placebo were –0.11 and –0.18, respectively.
A key secondary endpoint was sustained accumulation of disability. This was defined as an increase of at least 1 point on the Expanded Disability Status Scale (EDSS) from baseline that persisted for at least 12 weeks. The hazard ratios for the time to sustained accumulation of disability were 0.68 (P = .0442) for the 14-mg dose of teriflunomide and 0.95 for the 7-mg dose versus placebo.
"The safety and tolerability profile of teriflunomide, as characterized in this and previous studies, was similar for both the 7-mg and 14-mg doses, including long-term treatment observations," the investigators wrote. The most common side effects seen in patients treated with teriflunomide were hair thinning, headache, and increase in alanine aminotransferase concentrations.
Genzyme, a Sanofi company, sponsored the trial. The investigators disclosed financial relationships with Genzyme as well as other companies that manufacture drugs used to treat MS.
Teriflunomide significantly reduced the annualized relapse rate in patients with relapsing-remitting multiple sclerosis by more than one-third, compared with placebo, in the second of two large, randomized, phase III trials that have been conducted with the drug.
The latest study, called TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis), demonstrated that the 14-mg dose of teriflunomide produced a 36% relative risk reduction in the annualized relapse rate, compared with placebo (P = .0001). A 7-mg dose of the oral MS agent yielded a 22% relative risk reduction (P = .0183).
Teriflunomide 14 mg, but not 7 mg, was also associated with a significantly lower sustained disability accumulation than placebo.
"These data support the use of teriflunomide as an initial therapy for patients with relapsing-remitting multiple sclerosis and as an option for patients who are unable to tolerate other disease-modifying therapies," wrote the TOWER Trial Group investigators (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(13)70308-9]).
First author Dr. Christian Confavreux of University Claude Bernard Lyon 1, France, and his associates commented that the findings add to those previously reported from the phase III TEMSO trial (N. Engl. J. Med. 2011;365:1293-303), which showed that teriflunomide 7 mg and 14 mg both reduced the annualized relapse rate by around 31% when compared with placebo. They are also supported by the results of a phase II extension study.
Teriflunomide was approved for the treatment of adults with relapsing-remitting MS in the United States (trade name Aubagio) in 2012 and in Europe in 2013. The drug is the principal active metabolite in leflunomide, which is licensed for the treatment of rheumatoid arthritis.
The TOWER trial involved a total of 1,169 patients with relapsing-remitting MS who were randomized to treatment: 408 were assigned to teriflunomide 14 mg, 372 to teriflunomide 7 mg, and 389 to placebo. The mean age of patients at study entry was approximately 38 years, with just over 80% being of white, 15% of Asian, and 2% of black ethnicity.
The annualized relapse rates were 0.50 for patients treated with placebo, 0.32 for patients treated with teriflunomide 14 mg, and 0.39 for those treated with teriflunomide 7 mg. Absolute risk reductions for teriflunomide 14 mg and 7 mg versus placebo were –0.11 and –0.18, respectively.
A key secondary endpoint was sustained accumulation of disability. This was defined as an increase of at least 1 point on the Expanded Disability Status Scale (EDSS) from baseline that persisted for at least 12 weeks. The hazard ratios for the time to sustained accumulation of disability were 0.68 (P = .0442) for the 14-mg dose of teriflunomide and 0.95 for the 7-mg dose versus placebo.
"The safety and tolerability profile of teriflunomide, as characterized in this and previous studies, was similar for both the 7-mg and 14-mg doses, including long-term treatment observations," the investigators wrote. The most common side effects seen in patients treated with teriflunomide were hair thinning, headache, and increase in alanine aminotransferase concentrations.
Genzyme, a Sanofi company, sponsored the trial. The investigators disclosed financial relationships with Genzyme as well as other companies that manufacture drugs used to treat MS.
FROM THE LANCET NEUROLOGY
Major finding: The annualized relapse rate was 0.32 for patients treated with teriflunomide 14 mg versus 0.50 for placebo-treated patients (P = .0001).
Data source: An international, multicenter, double-blind, randomized, placebo-controlled phase III trial of 1,169 adults with relapsing-remitting multiple sclerosis.
Disclosures: Genzyme, a Sanofi company, sponsored the trial. The investigators disclosed financial relationships with Genzyme as well as other companies that manufacture drugs used to treat MS.