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Tocilizumab outperformed azathioprine for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in the first-ever head-to-head trial, according to data reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Fu-Dong Shi, Tianjin Medical University General Hospital in China.
Dr. Fu-Dong Shi

The tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorders (TANGO) trial, explained senior investigator Fu-Dong Shi, MD, PhD, tracked the time to first NMOSD relapse for patients randomized either to tocilizumab or azathioprine. After 60 weeks of participation in the head-to-head trial, 86% of patients receiving tocilizumab remained relapse-free, compared with 56.9% of those on azathioprine. By 90 weeks of therapy, the relapse-free rate held at 86% for those receiving tocilizumab, compared with 48.1% for those on azathioprine, for a 76.4% relative reduction in risk of relapse.
 

Patients with concomitant autoimmune disease saw particular benefit from tocilizumab compared with azathioprine. On tocilizumab, 78.8% of those with concomitant autoimmune disease remained relapse-free at 90 weeks, a rate that did not differ significantly from that seen in those without other autoimmune disease. However, 22.3% of those with concomitant autoimmune disease who received azathioprine remained relapse-free at 90 weeks, compared with 63.5% of those without autoimmune disease.

Dr. Shi, of the Tianjin (China) Medical University General Hospital, explained that there was limited evidence for the advantage of newer disease-modifying therapies (DMTs) over such older medications as azathioprine to treat NMOSD. Therefore, he said, he and other investigators in the Chinese Medical Network for Neuroinflammation (CMNN), including first author Chao Zhang, MD, initiated a randomized, multicenter, open-label trial that compared tocilizumab to azathioprine for highly relapsing NMOSD.

A total of 118 patients were enrolled. To participate, patients had to meet the 2015 international consensus criteria for NMOSD, and have had at least two relapses in the past year or three relapses within the preceding 2 years.

After a washout period, participants were randomized 1:1 to receive daily oral azathioprine dosed at 2-3 mg/kg or intravenous tocilizumab dosed at 8 mg/kg every 4 weeks. Participants continued on the assigned regimen for at least 60 weeks.

Secondary endpoints included 12-week confirmed disability progression. Here, 35.8% of those on azathioprine saw disability progression, compared with 9.9% on tocilizumab, for a 72.5% relative risk reduction. Serum aquaporin 4-IgG titers fell further for those taking tocilizumab.

In terms of safety, 83% of those on azathioprine and 61% of those receiving tocilizumab had a treatment-related adverse event, as determined by investigator assessment. About half of patients in each group experienced moderate adverse events, and about 90% had mild adverse events in each group. However, there were twice as many severe adverse events among those taking azathioprine. There was one NMOSD-related death in each group.

Subgroup analyses looked at baseline disability scores, number of previous relapses, disease duration, and age at randomization. None of these variables made a difference in the statistically better performance of tocilizumab compared with azathioprine, with hazard ratios ranging from 0.076 to 0.343 in favor of tocilizumab for all subgroups.

Patients were almost all female (92% overall) and about 47 years old at baseline, with a 6-year history of NMOSD.

Overall, 83% of the cohort had experienced optic neuritis over the preceding 2 years, and 94% had experienced acute myelitis. Other manifestations of NMOSD, such as acute brainstem syndrome and symptomatic cerebral syndrome, were much less frequent, occurring in 4%-30% of patients.

Most patients (71%) had been on oral corticosteroids before the washout period, and 34% had been taking mycophenolate mofetil. Azathioprine was taken by 44% of patients at baseline.

Additional data captured during the TANGO trial are being analyzed and will be reported at a later date, said Dr. Shi. These include optical coherence tomography and visual evoked potentials; magnetic resonance imaging of the brain, spinal cord, and optic nerve; and tracking serum B-cell subpopulations. He added that the investigators are continuing long-term, real-world follow-up of the TANGO patient cohort.

Dr. Shi acknowledged that TANGO was limited by the lack of an independent data monitoring committee and the open-label nature of the study.

The study was funded by Tianjin Medical University; Capital Medical University, Beijing; and the National Science Foundation of China. Dr. Shi and coauthors reported no conflicts of interest.
 

SOURCE: Zhang C et al. ECTRIMS 2019, Abstract 140.

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Tocilizumab outperformed azathioprine for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in the first-ever head-to-head trial, according to data reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Fu-Dong Shi, Tianjin Medical University General Hospital in China.
Dr. Fu-Dong Shi

The tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorders (TANGO) trial, explained senior investigator Fu-Dong Shi, MD, PhD, tracked the time to first NMOSD relapse for patients randomized either to tocilizumab or azathioprine. After 60 weeks of participation in the head-to-head trial, 86% of patients receiving tocilizumab remained relapse-free, compared with 56.9% of those on azathioprine. By 90 weeks of therapy, the relapse-free rate held at 86% for those receiving tocilizumab, compared with 48.1% for those on azathioprine, for a 76.4% relative reduction in risk of relapse.
 

Patients with concomitant autoimmune disease saw particular benefit from tocilizumab compared with azathioprine. On tocilizumab, 78.8% of those with concomitant autoimmune disease remained relapse-free at 90 weeks, a rate that did not differ significantly from that seen in those without other autoimmune disease. However, 22.3% of those with concomitant autoimmune disease who received azathioprine remained relapse-free at 90 weeks, compared with 63.5% of those without autoimmune disease.

Dr. Shi, of the Tianjin (China) Medical University General Hospital, explained that there was limited evidence for the advantage of newer disease-modifying therapies (DMTs) over such older medications as azathioprine to treat NMOSD. Therefore, he said, he and other investigators in the Chinese Medical Network for Neuroinflammation (CMNN), including first author Chao Zhang, MD, initiated a randomized, multicenter, open-label trial that compared tocilizumab to azathioprine for highly relapsing NMOSD.

A total of 118 patients were enrolled. To participate, patients had to meet the 2015 international consensus criteria for NMOSD, and have had at least two relapses in the past year or three relapses within the preceding 2 years.

After a washout period, participants were randomized 1:1 to receive daily oral azathioprine dosed at 2-3 mg/kg or intravenous tocilizumab dosed at 8 mg/kg every 4 weeks. Participants continued on the assigned regimen for at least 60 weeks.

Secondary endpoints included 12-week confirmed disability progression. Here, 35.8% of those on azathioprine saw disability progression, compared with 9.9% on tocilizumab, for a 72.5% relative risk reduction. Serum aquaporin 4-IgG titers fell further for those taking tocilizumab.

In terms of safety, 83% of those on azathioprine and 61% of those receiving tocilizumab had a treatment-related adverse event, as determined by investigator assessment. About half of patients in each group experienced moderate adverse events, and about 90% had mild adverse events in each group. However, there were twice as many severe adverse events among those taking azathioprine. There was one NMOSD-related death in each group.

Subgroup analyses looked at baseline disability scores, number of previous relapses, disease duration, and age at randomization. None of these variables made a difference in the statistically better performance of tocilizumab compared with azathioprine, with hazard ratios ranging from 0.076 to 0.343 in favor of tocilizumab for all subgroups.

Patients were almost all female (92% overall) and about 47 years old at baseline, with a 6-year history of NMOSD.

Overall, 83% of the cohort had experienced optic neuritis over the preceding 2 years, and 94% had experienced acute myelitis. Other manifestations of NMOSD, such as acute brainstem syndrome and symptomatic cerebral syndrome, were much less frequent, occurring in 4%-30% of patients.

Most patients (71%) had been on oral corticosteroids before the washout period, and 34% had been taking mycophenolate mofetil. Azathioprine was taken by 44% of patients at baseline.

Additional data captured during the TANGO trial are being analyzed and will be reported at a later date, said Dr. Shi. These include optical coherence tomography and visual evoked potentials; magnetic resonance imaging of the brain, spinal cord, and optic nerve; and tracking serum B-cell subpopulations. He added that the investigators are continuing long-term, real-world follow-up of the TANGO patient cohort.

Dr. Shi acknowledged that TANGO was limited by the lack of an independent data monitoring committee and the open-label nature of the study.

The study was funded by Tianjin Medical University; Capital Medical University, Beijing; and the National Science Foundation of China. Dr. Shi and coauthors reported no conflicts of interest.
 

SOURCE: Zhang C et al. ECTRIMS 2019, Abstract 140.

 

Tocilizumab outperformed azathioprine for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in the first-ever head-to-head trial, according to data reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Dr. Fu-Dong Shi, Tianjin Medical University General Hospital in China.
Dr. Fu-Dong Shi

The tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorders (TANGO) trial, explained senior investigator Fu-Dong Shi, MD, PhD, tracked the time to first NMOSD relapse for patients randomized either to tocilizumab or azathioprine. After 60 weeks of participation in the head-to-head trial, 86% of patients receiving tocilizumab remained relapse-free, compared with 56.9% of those on azathioprine. By 90 weeks of therapy, the relapse-free rate held at 86% for those receiving tocilizumab, compared with 48.1% for those on azathioprine, for a 76.4% relative reduction in risk of relapse.
 

Patients with concomitant autoimmune disease saw particular benefit from tocilizumab compared with azathioprine. On tocilizumab, 78.8% of those with concomitant autoimmune disease remained relapse-free at 90 weeks, a rate that did not differ significantly from that seen in those without other autoimmune disease. However, 22.3% of those with concomitant autoimmune disease who received azathioprine remained relapse-free at 90 weeks, compared with 63.5% of those without autoimmune disease.

Dr. Shi, of the Tianjin (China) Medical University General Hospital, explained that there was limited evidence for the advantage of newer disease-modifying therapies (DMTs) over such older medications as azathioprine to treat NMOSD. Therefore, he said, he and other investigators in the Chinese Medical Network for Neuroinflammation (CMNN), including first author Chao Zhang, MD, initiated a randomized, multicenter, open-label trial that compared tocilizumab to azathioprine for highly relapsing NMOSD.

A total of 118 patients were enrolled. To participate, patients had to meet the 2015 international consensus criteria for NMOSD, and have had at least two relapses in the past year or three relapses within the preceding 2 years.

After a washout period, participants were randomized 1:1 to receive daily oral azathioprine dosed at 2-3 mg/kg or intravenous tocilizumab dosed at 8 mg/kg every 4 weeks. Participants continued on the assigned regimen for at least 60 weeks.

Secondary endpoints included 12-week confirmed disability progression. Here, 35.8% of those on azathioprine saw disability progression, compared with 9.9% on tocilizumab, for a 72.5% relative risk reduction. Serum aquaporin 4-IgG titers fell further for those taking tocilizumab.

In terms of safety, 83% of those on azathioprine and 61% of those receiving tocilizumab had a treatment-related adverse event, as determined by investigator assessment. About half of patients in each group experienced moderate adverse events, and about 90% had mild adverse events in each group. However, there were twice as many severe adverse events among those taking azathioprine. There was one NMOSD-related death in each group.

Subgroup analyses looked at baseline disability scores, number of previous relapses, disease duration, and age at randomization. None of these variables made a difference in the statistically better performance of tocilizumab compared with azathioprine, with hazard ratios ranging from 0.076 to 0.343 in favor of tocilizumab for all subgroups.

Patients were almost all female (92% overall) and about 47 years old at baseline, with a 6-year history of NMOSD.

Overall, 83% of the cohort had experienced optic neuritis over the preceding 2 years, and 94% had experienced acute myelitis. Other manifestations of NMOSD, such as acute brainstem syndrome and symptomatic cerebral syndrome, were much less frequent, occurring in 4%-30% of patients.

Most patients (71%) had been on oral corticosteroids before the washout period, and 34% had been taking mycophenolate mofetil. Azathioprine was taken by 44% of patients at baseline.

Additional data captured during the TANGO trial are being analyzed and will be reported at a later date, said Dr. Shi. These include optical coherence tomography and visual evoked potentials; magnetic resonance imaging of the brain, spinal cord, and optic nerve; and tracking serum B-cell subpopulations. He added that the investigators are continuing long-term, real-world follow-up of the TANGO patient cohort.

Dr. Shi acknowledged that TANGO was limited by the lack of an independent data monitoring committee and the open-label nature of the study.

The study was funded by Tianjin Medical University; Capital Medical University, Beijing; and the National Science Foundation of China. Dr. Shi and coauthors reported no conflicts of interest.
 

SOURCE: Zhang C et al. ECTRIMS 2019, Abstract 140.

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