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James Meyer - One of the best experts on this subject based on the ideXlab platform.

  • potential mechanisms for prolonged loss of ambulation with Deflazacort in duchenne muscular dystrophy tolerability profile and effects on growth p5 059
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p<0.005), length percentile (p<0.05) and height percentile (p<0.002) were significantly less with Deflazacort than prednisone over 52 weeks of treatment. It also showed that Deflazacort-treated boys had significantly less weight gain (p<0.001) compared to prednisone. Conclusions: Deflazacort prolongs LoA in DMD patients. This may in part be due to the shorter stature and decreased weight gain with Deflazacort compared to prednisone, which allows for a biomechanical advantage. Better tolerability of Deflazacort compared to prednisone could also account for an improved efficacy profile in DMD patients. Additional studies are warranted to help elucidate the mechanism behind these effects. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • effect of Deflazacort and prednisone versus placebo on muscle strength in boys with duchenne muscular dystrophy who have lost ambulation results from the Deflazacort clinical trial program s28 006
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To assess the effects of Deflazacort and prednisone on muscle strength in boys with DMD who have lost ambulation Background: Duchenne Muscular Dystrophy (DMD) is the most common type of muscular dystrophy. Glucocorticoids are the mainstay of treatment in ambulatory patients, but often discontinued after boys have lost ambulation. Design/Methods: This randomized, double-blind, placebo-controlled, active comparator, Phase 3 study evaluated the efficacy of two Deflazacort doses (0.9 mg/kg/day and 1.2 mg/kg/day) compared to prednisone (0.75 mg/kg/day) and placebo for treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted a post-hoc subgroup analysis of muscle strength (using a modified 11-point medical research council scale) in patients who were non-ambulatory at baseline. Results: A total of 196 participants were randomized to the 4 treatment groups; 45 patients were non-ambulatory at baseline. At 12 weeks, both doses of Deflazacort and prednisone had numerical improvement in muscle strength while placebo patients worsened. Deflazacort at 1.2 mg/kg/day reached significance over placebo at 12 weeks (LS mean change of 0.49; p<0.05). Over 52 weeks of treatment, both Deflazacort groups showed numerical improvement in muscle strength while the prednisone group worsened [LS mean change vs. prednisone of 0.27 for Deflazacort 0.9 mg/kg/day (p=0.387) and 0.45 for Deflazacort 1.2 mg/kg/day (p=0.088)]. Conclusions: This is the first prospective, randomized, blinded study to demonstrate the effects of Deflazacort and prednisone on muscle strength in non-ambulatory boys with DMD. In this small, sub-set analysis, Deflazacort demonstrated trends in improving muscle strength in boys who had lost ambulation. Although the recommended dose of Deflazacort is 0.9 mg/kg/day, increased doses may be required to preserve motor function in post- ambulatory boys; these data merit further investigation. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • a comparison of the effects of Deflazacort and prednisone versus placebo on timed functional tests in boys with duchenne muscular dystrophy p5 005
    Neurology, 2016
    Co-Authors: James Meyer, T Cunniff, S Wanaski, J Dubow
    Abstract:

    Objective: To describe the timed motor performance of standing from lying position, climbing 4 stairs, and running or walking 30 feet in patients taking Deflazacort, prednisone, or placebo. Background: The measurement of timed functional tests (TFTs) are commonly used to evaluate children with Duchenne muscular dystrophy (DMD). As muscle weakness progresses, compensatory movements are used to perform the tasks, resulting in higher measured times. Corticosteroids have demonstrated clinical benefit in the treatment of DMD including performance in timed function tests. Design/Methods: In a randomized, double-blind, placebo-controlled, active comparator, Phase 3 study, the efficacy of two doses of Deflazacort (0.9 mg/kg/day and 1.2 mg/kg/day) was compared to prednisone (0.75 mg/kg/day) and placebo for the treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted an analysis of timed functional tests to compare treatment and placebo groups Results: TFTs showed statistically significant differences between active treatments and placebo in times from supine to standing, climbing 4 stairs, and time to run/walk 30 feet at 12 weeks (p<0.002). At 12 weeks there was a trend towards significant improvement with Deflazacort 0.9 mg/kg/day vs. prednisone in time to climb 4 stairs (p=0.066). From baseline to 52 weeks, both doses of Deflazacort had numerically greater improvement in TFTs compared to prednisone. However, only time to climb 4 stairs reached significance with Deflazacort 0.9 mg/kg/day (p<0.05) and time to run/walk 30 feet trended towards significance with Deflazacort 1.2 mg/kg/day (p=0.07) vs. prednisone. Conclusions: Both Deflazacort and prednisone demonstrated significant improvement versus placebo in timed functional testing. Benefits were sustained over 52 weeks with both Deflazacort and prednisone, but Deflazacort appeared to have some benefits compared to prednisone in certain motor functions. Disclosure: Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

  • Potential Mechanisms for Prolonged Loss of Ambulation with Deflazacort in Duchenne Muscular Dystrophy - Tolerability Profile and Effects on Growth (P5.059)
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p

  • effects of Deflazacort on growth and development in juvenile rats p5 097
    Neurology, 2016
    Co-Authors: S Wanaski, J Dubow, James Meyer, Elise M Lewis, T Cunniff
    Abstract:

    Objective: To determine the toxicological, behavioral, and neurohistopathological effects of Deflazacort in juvenile rats from Postnatal Day (PND) 21 to 80 with recovery at PND 138. Background: Marathon is developing Deflazacort for the treatment of boys with Duchenne Muscular Dystrophy (DMD). Despite extensive clinical experience with Deflazacort, its effects on growth and development have not been characterized in juvenile animals. Methods: Juvenile rats (N=20/sex/group) were administered 0, 0.1, 0.3, or 1.0 mg/kg/day Deflazacort from PND21-80 and assessed for clinical observations, body weight, food consumption, ophthalmologic examinations, behavioral assessments (FOB, acoustic startle response, motor activity, Morris Water Maze), clinical pathology (hematology, clinical chemistry, urinalysis), bone measurements, macroscopic and microscopic observations, male reproductive assessments, organ weights, and neurohistopathology evaluations. A satellite group of juvenile rats was dosed to provide toxicokinetic exposures. Results: At the end of the dosing period, Deflazacort-related effects were dose-dependent and included: decreases in mean body weight gain and food consumption; increases in stereotypical behavior and motor activity at higher doses; mild to marked deceases in total white blood cell and lymphocyte counts, mild increases in neutrophil counts, and mild to moderate decreases in cholesterol; decreases in femur lengths; decreases in adrenal glands, spleen, and thymus weights; and correlative histopathological findings of decreased cellularity in the target lymphoid tissues. There were no Deflazacort-related findings on ophthalmic exams, spermatogenesis, or neurohistopathology. At the end of the recovery period, Deflazacort-related effects demonstrated complete recovery (clinical pathology, histopathology) or near complete recovery (body weight gain, neurobehavioral assessments). Conclusions: Deflazacort-related effects on growth and development in juvenile rats were consistent with the primary pharmacology of the drug. All findings demonstrated signs of recovery upon cessation of dosing. Exposures to the active metabolite of Deflazacort in the rats were about 2-fold higher than exposures anticipated in boys with DMD at therapeutic doses of Deflazacort. Disclosure: Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Lewis has nothing to disclose. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

T Cunniff - One of the best experts on this subject based on the ideXlab platform.

  • potential mechanisms for prolonged loss of ambulation with Deflazacort in duchenne muscular dystrophy tolerability profile and effects on growth p5 059
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p<0.005), length percentile (p<0.05) and height percentile (p<0.002) were significantly less with Deflazacort than prednisone over 52 weeks of treatment. It also showed that Deflazacort-treated boys had significantly less weight gain (p<0.001) compared to prednisone. Conclusions: Deflazacort prolongs LoA in DMD patients. This may in part be due to the shorter stature and decreased weight gain with Deflazacort compared to prednisone, which allows for a biomechanical advantage. Better tolerability of Deflazacort compared to prednisone could also account for an improved efficacy profile in DMD patients. Additional studies are warranted to help elucidate the mechanism behind these effects. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • effect of Deflazacort and prednisone versus placebo on muscle strength in boys with duchenne muscular dystrophy who have lost ambulation results from the Deflazacort clinical trial program s28 006
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To assess the effects of Deflazacort and prednisone on muscle strength in boys with DMD who have lost ambulation Background: Duchenne Muscular Dystrophy (DMD) is the most common type of muscular dystrophy. Glucocorticoids are the mainstay of treatment in ambulatory patients, but often discontinued after boys have lost ambulation. Design/Methods: This randomized, double-blind, placebo-controlled, active comparator, Phase 3 study evaluated the efficacy of two Deflazacort doses (0.9 mg/kg/day and 1.2 mg/kg/day) compared to prednisone (0.75 mg/kg/day) and placebo for treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted a post-hoc subgroup analysis of muscle strength (using a modified 11-point medical research council scale) in patients who were non-ambulatory at baseline. Results: A total of 196 participants were randomized to the 4 treatment groups; 45 patients were non-ambulatory at baseline. At 12 weeks, both doses of Deflazacort and prednisone had numerical improvement in muscle strength while placebo patients worsened. Deflazacort at 1.2 mg/kg/day reached significance over placebo at 12 weeks (LS mean change of 0.49; p<0.05). Over 52 weeks of treatment, both Deflazacort groups showed numerical improvement in muscle strength while the prednisone group worsened [LS mean change vs. prednisone of 0.27 for Deflazacort 0.9 mg/kg/day (p=0.387) and 0.45 for Deflazacort 1.2 mg/kg/day (p=0.088)]. Conclusions: This is the first prospective, randomized, blinded study to demonstrate the effects of Deflazacort and prednisone on muscle strength in non-ambulatory boys with DMD. In this small, sub-set analysis, Deflazacort demonstrated trends in improving muscle strength in boys who had lost ambulation. Although the recommended dose of Deflazacort is 0.9 mg/kg/day, increased doses may be required to preserve motor function in post- ambulatory boys; these data merit further investigation. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • a comparison of the effects of Deflazacort and prednisone versus placebo on timed functional tests in boys with duchenne muscular dystrophy p5 005
    Neurology, 2016
    Co-Authors: James Meyer, T Cunniff, S Wanaski, J Dubow
    Abstract:

    Objective: To describe the timed motor performance of standing from lying position, climbing 4 stairs, and running or walking 30 feet in patients taking Deflazacort, prednisone, or placebo. Background: The measurement of timed functional tests (TFTs) are commonly used to evaluate children with Duchenne muscular dystrophy (DMD). As muscle weakness progresses, compensatory movements are used to perform the tasks, resulting in higher measured times. Corticosteroids have demonstrated clinical benefit in the treatment of DMD including performance in timed function tests. Design/Methods: In a randomized, double-blind, placebo-controlled, active comparator, Phase 3 study, the efficacy of two doses of Deflazacort (0.9 mg/kg/day and 1.2 mg/kg/day) was compared to prednisone (0.75 mg/kg/day) and placebo for the treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted an analysis of timed functional tests to compare treatment and placebo groups Results: TFTs showed statistically significant differences between active treatments and placebo in times from supine to standing, climbing 4 stairs, and time to run/walk 30 feet at 12 weeks (p<0.002). At 12 weeks there was a trend towards significant improvement with Deflazacort 0.9 mg/kg/day vs. prednisone in time to climb 4 stairs (p=0.066). From baseline to 52 weeks, both doses of Deflazacort had numerically greater improvement in TFTs compared to prednisone. However, only time to climb 4 stairs reached significance with Deflazacort 0.9 mg/kg/day (p<0.05) and time to run/walk 30 feet trended towards significance with Deflazacort 1.2 mg/kg/day (p=0.07) vs. prednisone. Conclusions: Both Deflazacort and prednisone demonstrated significant improvement versus placebo in timed functional testing. Benefits were sustained over 52 weeks with both Deflazacort and prednisone, but Deflazacort appeared to have some benefits compared to prednisone in certain motor functions. Disclosure: Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

  • Potential Mechanisms for Prolonged Loss of Ambulation with Deflazacort in Duchenne Muscular Dystrophy - Tolerability Profile and Effects on Growth (P5.059)
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p

  • effects of Deflazacort on growth and development in juvenile rats p5 097
    Neurology, 2016
    Co-Authors: S Wanaski, J Dubow, James Meyer, Elise M Lewis, T Cunniff
    Abstract:

    Objective: To determine the toxicological, behavioral, and neurohistopathological effects of Deflazacort in juvenile rats from Postnatal Day (PND) 21 to 80 with recovery at PND 138. Background: Marathon is developing Deflazacort for the treatment of boys with Duchenne Muscular Dystrophy (DMD). Despite extensive clinical experience with Deflazacort, its effects on growth and development have not been characterized in juvenile animals. Methods: Juvenile rats (N=20/sex/group) were administered 0, 0.1, 0.3, or 1.0 mg/kg/day Deflazacort from PND21-80 and assessed for clinical observations, body weight, food consumption, ophthalmologic examinations, behavioral assessments (FOB, acoustic startle response, motor activity, Morris Water Maze), clinical pathology (hematology, clinical chemistry, urinalysis), bone measurements, macroscopic and microscopic observations, male reproductive assessments, organ weights, and neurohistopathology evaluations. A satellite group of juvenile rats was dosed to provide toxicokinetic exposures. Results: At the end of the dosing period, Deflazacort-related effects were dose-dependent and included: decreases in mean body weight gain and food consumption; increases in stereotypical behavior and motor activity at higher doses; mild to marked deceases in total white blood cell and lymphocyte counts, mild increases in neutrophil counts, and mild to moderate decreases in cholesterol; decreases in femur lengths; decreases in adrenal glands, spleen, and thymus weights; and correlative histopathological findings of decreased cellularity in the target lymphoid tissues. There were no Deflazacort-related findings on ophthalmic exams, spermatogenesis, or neurohistopathology. At the end of the recovery period, Deflazacort-related effects demonstrated complete recovery (clinical pathology, histopathology) or near complete recovery (body weight gain, neurobehavioral assessments). Conclusions: Deflazacort-related effects on growth and development in juvenile rats were consistent with the primary pharmacology of the drug. All findings demonstrated signs of recovery upon cessation of dosing. Exposures to the active metabolite of Deflazacort in the rats were about 2-fold higher than exposures anticipated in boys with DMD at therapeutic doses of Deflazacort. Disclosure: Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Lewis has nothing to disclose. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

J Dubow - One of the best experts on this subject based on the ideXlab platform.

  • potential mechanisms for prolonged loss of ambulation with Deflazacort in duchenne muscular dystrophy tolerability profile and effects on growth p5 059
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p<0.005), length percentile (p<0.05) and height percentile (p<0.002) were significantly less with Deflazacort than prednisone over 52 weeks of treatment. It also showed that Deflazacort-treated boys had significantly less weight gain (p<0.001) compared to prednisone. Conclusions: Deflazacort prolongs LoA in DMD patients. This may in part be due to the shorter stature and decreased weight gain with Deflazacort compared to prednisone, which allows for a biomechanical advantage. Better tolerability of Deflazacort compared to prednisone could also account for an improved efficacy profile in DMD patients. Additional studies are warranted to help elucidate the mechanism behind these effects. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • effect of Deflazacort and prednisone versus placebo on muscle strength in boys with duchenne muscular dystrophy who have lost ambulation results from the Deflazacort clinical trial program s28 006
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To assess the effects of Deflazacort and prednisone on muscle strength in boys with DMD who have lost ambulation Background: Duchenne Muscular Dystrophy (DMD) is the most common type of muscular dystrophy. Glucocorticoids are the mainstay of treatment in ambulatory patients, but often discontinued after boys have lost ambulation. Design/Methods: This randomized, double-blind, placebo-controlled, active comparator, Phase 3 study evaluated the efficacy of two Deflazacort doses (0.9 mg/kg/day and 1.2 mg/kg/day) compared to prednisone (0.75 mg/kg/day) and placebo for treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted a post-hoc subgroup analysis of muscle strength (using a modified 11-point medical research council scale) in patients who were non-ambulatory at baseline. Results: A total of 196 participants were randomized to the 4 treatment groups; 45 patients were non-ambulatory at baseline. At 12 weeks, both doses of Deflazacort and prednisone had numerical improvement in muscle strength while placebo patients worsened. Deflazacort at 1.2 mg/kg/day reached significance over placebo at 12 weeks (LS mean change of 0.49; p<0.05). Over 52 weeks of treatment, both Deflazacort groups showed numerical improvement in muscle strength while the prednisone group worsened [LS mean change vs. prednisone of 0.27 for Deflazacort 0.9 mg/kg/day (p=0.387) and 0.45 for Deflazacort 1.2 mg/kg/day (p=0.088)]. Conclusions: This is the first prospective, randomized, blinded study to demonstrate the effects of Deflazacort and prednisone on muscle strength in non-ambulatory boys with DMD. In this small, sub-set analysis, Deflazacort demonstrated trends in improving muscle strength in boys who had lost ambulation. Although the recommended dose of Deflazacort is 0.9 mg/kg/day, increased doses may be required to preserve motor function in post- ambulatory boys; these data merit further investigation. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • a comparison of the effects of Deflazacort and prednisone versus placebo on timed functional tests in boys with duchenne muscular dystrophy p5 005
    Neurology, 2016
    Co-Authors: James Meyer, T Cunniff, S Wanaski, J Dubow
    Abstract:

    Objective: To describe the timed motor performance of standing from lying position, climbing 4 stairs, and running or walking 30 feet in patients taking Deflazacort, prednisone, or placebo. Background: The measurement of timed functional tests (TFTs) are commonly used to evaluate children with Duchenne muscular dystrophy (DMD). As muscle weakness progresses, compensatory movements are used to perform the tasks, resulting in higher measured times. Corticosteroids have demonstrated clinical benefit in the treatment of DMD including performance in timed function tests. Design/Methods: In a randomized, double-blind, placebo-controlled, active comparator, Phase 3 study, the efficacy of two doses of Deflazacort (0.9 mg/kg/day and 1.2 mg/kg/day) was compared to prednisone (0.75 mg/kg/day) and placebo for the treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted an analysis of timed functional tests to compare treatment and placebo groups Results: TFTs showed statistically significant differences between active treatments and placebo in times from supine to standing, climbing 4 stairs, and time to run/walk 30 feet at 12 weeks (p<0.002). At 12 weeks there was a trend towards significant improvement with Deflazacort 0.9 mg/kg/day vs. prednisone in time to climb 4 stairs (p=0.066). From baseline to 52 weeks, both doses of Deflazacort had numerically greater improvement in TFTs compared to prednisone. However, only time to climb 4 stairs reached significance with Deflazacort 0.9 mg/kg/day (p<0.05) and time to run/walk 30 feet trended towards significance with Deflazacort 1.2 mg/kg/day (p=0.07) vs. prednisone. Conclusions: Both Deflazacort and prednisone demonstrated significant improvement versus placebo in timed functional testing. Benefits were sustained over 52 weeks with both Deflazacort and prednisone, but Deflazacort appeared to have some benefits compared to prednisone in certain motor functions. Disclosure: Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

  • Potential Mechanisms for Prolonged Loss of Ambulation with Deflazacort in Duchenne Muscular Dystrophy - Tolerability Profile and Effects on Growth (P5.059)
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p

  • effects of Deflazacort on growth and development in juvenile rats p5 097
    Neurology, 2016
    Co-Authors: S Wanaski, J Dubow, James Meyer, Elise M Lewis, T Cunniff
    Abstract:

    Objective: To determine the toxicological, behavioral, and neurohistopathological effects of Deflazacort in juvenile rats from Postnatal Day (PND) 21 to 80 with recovery at PND 138. Background: Marathon is developing Deflazacort for the treatment of boys with Duchenne Muscular Dystrophy (DMD). Despite extensive clinical experience with Deflazacort, its effects on growth and development have not been characterized in juvenile animals. Methods: Juvenile rats (N=20/sex/group) were administered 0, 0.1, 0.3, or 1.0 mg/kg/day Deflazacort from PND21-80 and assessed for clinical observations, body weight, food consumption, ophthalmologic examinations, behavioral assessments (FOB, acoustic startle response, motor activity, Morris Water Maze), clinical pathology (hematology, clinical chemistry, urinalysis), bone measurements, macroscopic and microscopic observations, male reproductive assessments, organ weights, and neurohistopathology evaluations. A satellite group of juvenile rats was dosed to provide toxicokinetic exposures. Results: At the end of the dosing period, Deflazacort-related effects were dose-dependent and included: decreases in mean body weight gain and food consumption; increases in stereotypical behavior and motor activity at higher doses; mild to marked deceases in total white blood cell and lymphocyte counts, mild increases in neutrophil counts, and mild to moderate decreases in cholesterol; decreases in femur lengths; decreases in adrenal glands, spleen, and thymus weights; and correlative histopathological findings of decreased cellularity in the target lymphoid tissues. There were no Deflazacort-related findings on ophthalmic exams, spermatogenesis, or neurohistopathology. At the end of the recovery period, Deflazacort-related effects demonstrated complete recovery (clinical pathology, histopathology) or near complete recovery (body weight gain, neurobehavioral assessments). Conclusions: Deflazacort-related effects on growth and development in juvenile rats were consistent with the primary pharmacology of the drug. All findings demonstrated signs of recovery upon cessation of dosing. Exposures to the active metabolite of Deflazacort in the rats were about 2-fold higher than exposures anticipated in boys with DMD at therapeutic doses of Deflazacort. Disclosure: Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Lewis has nothing to disclose. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

S Wanaski - One of the best experts on this subject based on the ideXlab platform.

  • potential mechanisms for prolonged loss of ambulation with Deflazacort in duchenne muscular dystrophy tolerability profile and effects on growth p5 059
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p<0.005), length percentile (p<0.05) and height percentile (p<0.002) were significantly less with Deflazacort than prednisone over 52 weeks of treatment. It also showed that Deflazacort-treated boys had significantly less weight gain (p<0.001) compared to prednisone. Conclusions: Deflazacort prolongs LoA in DMD patients. This may in part be due to the shorter stature and decreased weight gain with Deflazacort compared to prednisone, which allows for a biomechanical advantage. Better tolerability of Deflazacort compared to prednisone could also account for an improved efficacy profile in DMD patients. Additional studies are warranted to help elucidate the mechanism behind these effects. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • effect of Deflazacort and prednisone versus placebo on muscle strength in boys with duchenne muscular dystrophy who have lost ambulation results from the Deflazacort clinical trial program s28 006
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To assess the effects of Deflazacort and prednisone on muscle strength in boys with DMD who have lost ambulation Background: Duchenne Muscular Dystrophy (DMD) is the most common type of muscular dystrophy. Glucocorticoids are the mainstay of treatment in ambulatory patients, but often discontinued after boys have lost ambulation. Design/Methods: This randomized, double-blind, placebo-controlled, active comparator, Phase 3 study evaluated the efficacy of two Deflazacort doses (0.9 mg/kg/day and 1.2 mg/kg/day) compared to prednisone (0.75 mg/kg/day) and placebo for treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted a post-hoc subgroup analysis of muscle strength (using a modified 11-point medical research council scale) in patients who were non-ambulatory at baseline. Results: A total of 196 participants were randomized to the 4 treatment groups; 45 patients were non-ambulatory at baseline. At 12 weeks, both doses of Deflazacort and prednisone had numerical improvement in muscle strength while placebo patients worsened. Deflazacort at 1.2 mg/kg/day reached significance over placebo at 12 weeks (LS mean change of 0.49; p<0.05). Over 52 weeks of treatment, both Deflazacort groups showed numerical improvement in muscle strength while the prednisone group worsened [LS mean change vs. prednisone of 0.27 for Deflazacort 0.9 mg/kg/day (p=0.387) and 0.45 for Deflazacort 1.2 mg/kg/day (p=0.088)]. Conclusions: This is the first prospective, randomized, blinded study to demonstrate the effects of Deflazacort and prednisone on muscle strength in non-ambulatory boys with DMD. In this small, sub-set analysis, Deflazacort demonstrated trends in improving muscle strength in boys who had lost ambulation. Although the recommended dose of Deflazacort is 0.9 mg/kg/day, increased doses may be required to preserve motor function in post- ambulatory boys; these data merit further investigation. Disclosure: Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals.

  • a comparison of the effects of Deflazacort and prednisone versus placebo on timed functional tests in boys with duchenne muscular dystrophy p5 005
    Neurology, 2016
    Co-Authors: James Meyer, T Cunniff, S Wanaski, J Dubow
    Abstract:

    Objective: To describe the timed motor performance of standing from lying position, climbing 4 stairs, and running or walking 30 feet in patients taking Deflazacort, prednisone, or placebo. Background: The measurement of timed functional tests (TFTs) are commonly used to evaluate children with Duchenne muscular dystrophy (DMD). As muscle weakness progresses, compensatory movements are used to perform the tasks, resulting in higher measured times. Corticosteroids have demonstrated clinical benefit in the treatment of DMD including performance in timed function tests. Design/Methods: In a randomized, double-blind, placebo-controlled, active comparator, Phase 3 study, the efficacy of two doses of Deflazacort (0.9 mg/kg/day and 1.2 mg/kg/day) was compared to prednisone (0.75 mg/kg/day) and placebo for the treatment of boys with DMD. The first segment compared Deflazacort and prednisone to placebo over 12 weeks. The second segment compared the two doses of Deflazacort to prednisone from 12 to 52 weeks. We conducted an analysis of timed functional tests to compare treatment and placebo groups Results: TFTs showed statistically significant differences between active treatments and placebo in times from supine to standing, climbing 4 stairs, and time to run/walk 30 feet at 12 weeks (p<0.002). At 12 weeks there was a trend towards significant improvement with Deflazacort 0.9 mg/kg/day vs. prednisone in time to climb 4 stairs (p=0.066). From baseline to 52 weeks, both doses of Deflazacort had numerically greater improvement in TFTs compared to prednisone. However, only time to climb 4 stairs reached significance with Deflazacort 0.9 mg/kg/day (p<0.05) and time to run/walk 30 feet trended towards significance with Deflazacort 1.2 mg/kg/day (p=0.07) vs. prednisone. Conclusions: Both Deflazacort and prednisone demonstrated significant improvement versus placebo in timed functional testing. Benefits were sustained over 52 weeks with both Deflazacort and prednisone, but Deflazacort appeared to have some benefits compared to prednisone in certain motor functions. Disclosure: Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

  • Potential Mechanisms for Prolonged Loss of Ambulation with Deflazacort in Duchenne Muscular Dystrophy - Tolerability Profile and Effects on Growth (P5.059)
    Neurology, 2016
    Co-Authors: T Cunniff, S Wanaski, J Dubow, James Meyer
    Abstract:

    Objective: To summarize prolonged loss of ambulation (LoA) data for Deflazacort in Duchenne Muscular Dystrophy (DMD) patients and propose a mechanism for this finding based on randomized, controlled clinical trial data Background: DMD is an X-linked disease that affects approximately 1 in 5,000 live male births. Without treatment, boys lose ambulation in their pre- teens due to deterioration of muscle strength and eventually succumb to respiratory, orthopedic, and/or cardiac complications at a mean age ~19 years. Deflazacort has demonstrated profound clinical benefit on the course of the disease. Design/Methods: We summarized published data demonstrating Deflazacort delays time to LoA in DMD patients compared to non-steroid treated boys and compared to prednisone. Growth and weight gain data from a randomized, controlled, double-blind, placebo-controlled and active comparator, 52-week study for the treatment of DMD may help explain the difference in efficacy (Deflazacort 0.9 mg/kg/day and 1.2 mg/kg/day vs. prednisone 0.75 mg/kg/day) Results: Previously published studies established that treatment with Deflazacort prolongs ambulation compared to no-treatment. Additional published clinical investigations demonstrated that Deflazacort prolongs ambulation compared to prednisone. One study found that Deflazacort-treated boys maintained a chronic therapeutic dose compared to prednisone. The current randomized study demonstrated that forearm length (p

  • effects of Deflazacort on growth and development in juvenile rats p5 097
    Neurology, 2016
    Co-Authors: S Wanaski, J Dubow, James Meyer, Elise M Lewis, T Cunniff
    Abstract:

    Objective: To determine the toxicological, behavioral, and neurohistopathological effects of Deflazacort in juvenile rats from Postnatal Day (PND) 21 to 80 with recovery at PND 138. Background: Marathon is developing Deflazacort for the treatment of boys with Duchenne Muscular Dystrophy (DMD). Despite extensive clinical experience with Deflazacort, its effects on growth and development have not been characterized in juvenile animals. Methods: Juvenile rats (N=20/sex/group) were administered 0, 0.1, 0.3, or 1.0 mg/kg/day Deflazacort from PND21-80 and assessed for clinical observations, body weight, food consumption, ophthalmologic examinations, behavioral assessments (FOB, acoustic startle response, motor activity, Morris Water Maze), clinical pathology (hematology, clinical chemistry, urinalysis), bone measurements, macroscopic and microscopic observations, male reproductive assessments, organ weights, and neurohistopathology evaluations. A satellite group of juvenile rats was dosed to provide toxicokinetic exposures. Results: At the end of the dosing period, Deflazacort-related effects were dose-dependent and included: decreases in mean body weight gain and food consumption; increases in stereotypical behavior and motor activity at higher doses; mild to marked deceases in total white blood cell and lymphocyte counts, mild increases in neutrophil counts, and mild to moderate decreases in cholesterol; decreases in femur lengths; decreases in adrenal glands, spleen, and thymus weights; and correlative histopathological findings of decreased cellularity in the target lymphoid tissues. There were no Deflazacort-related findings on ophthalmic exams, spermatogenesis, or neurohistopathology. At the end of the recovery period, Deflazacort-related effects demonstrated complete recovery (clinical pathology, histopathology) or near complete recovery (body weight gain, neurobehavioral assessments). Conclusions: Deflazacort-related effects on growth and development in juvenile rats were consistent with the primary pharmacology of the drug. All findings demonstrated signs of recovery upon cessation of dosing. Exposures to the active metabolite of Deflazacort in the rats were about 2-fold higher than exposures anticipated in boys with DMD at therapeutic doses of Deflazacort. Disclosure: Dr. Wanaski has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Lewis has nothing to disclose. Dr. Dubow has received personal compensation for activities with Marathon Pharmaceuticals, LLC. Dr. Meyer has received personal compensation for activities with Marathon Pharmaceuticals. Dr. Cunniff has received personal compensation for activities with Marathon Pharmaceuticals, LLC.

Jorge R Ferraris - One of the best experts on this subject based on the ideXlab platform.

  • effects of Deflazacort vs methylprednisone a randomized study in kidney transplant patients
    Pediatric Nephrology, 2007
    Co-Authors: Jorge R Ferraris, Titania Pasqualini, Guillermo Alonso, Patricia Sorroche, A M Galich, Hector Jasper
    Abstract:

    Metabolic effects of Deflazacort vs. methylprednisone were studied in prepubertal patients after kidney transplantation. Thirty-one patients participated: 15 received Deflazacort and 16 remained on methylprednisone. The study started at a mean of 2.1 years after transplantation, when patients were randomized to either continue with methylprednisone or switch to Deflazacort. Height velocity increased more in the Deflazacort than in the methylprednisone group only during the first 2 years: 5.4 ± 0.5 vs. 3.5 ± 0.3 cm/year, and 4.2 ± 0.8 vs. 2.2 ± 0.4 cm/year p = 0.007, [by two-way analysis of variance (ANOVA)]. After 2 and 3 years, the number of patients who were overweight increased in the methylprednisone group and decreased in the Deflazacort group; p 7, was associated (p < 0.05) with the Deflazacort group. Our data suggest that Deflazacort therapy might improve linear growth and lean body mass and prevent excessive bone loss and fat accumulation. It also leads to an improvement in lipoprotein profile without reduction in insulin sensitivity.

  • effect of Deflazacort versus methylprednisone on growth body composition lipid profile and bone mass after renal transplantation
    Pediatric Nephrology, 2000
    Co-Authors: Jorge R Ferraris, Titania Pasqualini, Patricia Sorroche, A M Galich, Patricia Pennisi, Horacio M Domene, Hector Jasper
    Abstract:

    Kidney function, growth velocity, weight/ height ratio, body composition, lipid profile, and bone mass were studied in a randomized, multicenter trial of Deflazacort versus methylprednisone in 27 prepubertal patients with kidney transplantation. Methylprednisone (0.20±0.03) was replaced by Deflazacort (13 patients, 0.30±0.03 mg/kg per day). After 12 months, creatinine clearance decreased significantly only during methylprednisone therapy. Growth velocity increased only in patients treated with Deflazacort from 3.3±0.6 to 5.6±0.5 cm/year. Serum levels of several components of the insulin-like growth factor axis did not change. Weight/height ratio was increased in methylprednisone-treated patients (P<0.05) and decreased in Deflazacort-treated patients (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and serum leptin increased only in methylprednisone-treated patients (P<0.025). Total cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone-treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein-cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11% (P<0.005) in Deflazacort-treated patients. Total skeleton and lumbar spine bone mineral density decreased in both groups, but at 1 year methylprednisone-treated patients had lost 50% more bone. Bone mineral content decreased only in methylprednisone-treated patients (P<0.01). Our data suggest that substituting Deflazacort for maintenance methylprednisone might prevent height loss, excessive bone loss, and fat accumulation; and leads to an improvement in the lipoproteins of these children.

  • Effect of therapy with Deflazacort on dyslipoproteinemia after pediatric renal transplantation.
    The Journal of Pediatrics, 1998
    Co-Authors: Jorge R Ferraris, Patricia Sorroche, José Oyhamburu, Pedro Brandi, Titania Pasqualini
    Abstract:

    Deflazacort is an oxazolone compound derived from prednisolone, with similar immunosuppressive action but fewer side effects. Kidney function, weight/height ratio, serum triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were studied before and 6 months after substitution of Deflazacort (mean ± SEM, 0.3 ± 0.1 mg/kg per day) for methylprednisone (0.2 ± 0.1 mg/kg per day) in 14 patients treated with cyclosporine, aged 3.1 to 20.3 years, 3 years after renal transplantation. Serum creatinine and calculated creatinine clearance did not change significantly, and weight/height ratio decreased from 20.0% ± 7.1% to 12.5% ± 6.5% (P < .005) during Deflazacort therapy. Total cholesterol was reduced by 15.9% (from 233 ± 15 mg/dL to 196 ± 13 mg/dL, P < .01), LDL cholesterol by 25.5% (from 153 ± 14 mg/dL to 114 ± 12 mg/dL, P < .01), and TC/HDL cholesterol ratio by 28.3% (from 5.3 ± 0.4 to 3.8 ± 0.4, P < .01), whereas HDL cholesterol increased 18% (from 45 ± 2 mg/dL to 53 ± 2 mg/dL) and apolipoprotein A by 8.3% (from 122 ± 5 mg/dL to 132 ± 5 mg/dL, P < .05) during Deflazacort therapy. Our data suggest that substituting Deflazacort for maintenance methylprednisone therapy leads to an improvement in the lipoprotein profile of children after renal transplantation. (J Pediatr 1998;133:533-6)

  • effects of Deflazacort immunosuppression on long term growth and growth factors after renal transplantation
    Pediatric Nephrology, 1997
    Co-Authors: Jorge R Ferraris, Titania Pasqualini, Patricia Pennisi, Hector Jasper
    Abstract:

    Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of Deflazacort for methylprednisone in 27 transplanted patients aged 3.1 – 20 years. Methylprednisone (mean±SEM 0.17±0.01 mg/kg per day) was replaced by Deflazacort (0.29±0.01 mg/kg per day) for a period of 1 – 5 years. Calculated creatinine clearance did not change significantly during Deflazacort treatment. Growth velocity increased from 2.6±0.5 cm/year to 5.2±0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of Deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein -3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and -II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during Deflazacort therapy. Our findings suggest that immunosuppressive treatment with Deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.

  • effect of therapy with a new glucocorticoid Deflazacort on linear growth and growth hormone secretion after renal transplantation
    The Journal of Pediatrics, 1992
    Co-Authors: Jorge R Ferraris, Raul Gutman, E Granillo, Jose A Ramirez, Susana Ruiz, Titania Pasqualini
    Abstract:

    Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of Deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Taner pubertal stage 1. Methylprednisone (mean±SEM: 0.2±0.02 mg/kg per day) was replaced by Deflazacort (0.3±0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during Deflazacort treatment. Growth velocity increased from 1.5±0.3 to 3.2±0.5 cm/yr ( p p p