CMSC 2017

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.