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A randomized, double-blind, placebo-controlled clinical study

EVALUATED THE EFFICACY AND SAFETY OF ACTHAR GEL VS PLACEBO IN PATIENTS WITH ACUTE MS RELAPSE1

Study Design1

In a randomized, double-blind, placebo-controlled study, patients with acute MS relapses were given Acthar Gel (n=103) or placebo gel (n=94) intramuscularly as follows:

Neurologic evaluations were performed within 24 hours before treatment, on Days 7 and 14 during treatment, and on Days 7 and 14 after treatment. Clinical assessments included:

About Overall Condition: The estimate of overall condition is a subjective measure designed to evaluate change in the patient’s condition as a whole, regardless of the nature or extent of the specific neurologic deficits that may have changed. Clinicians used their experience to judge whether a patient’s pretreatment condition was improved, worse, or the same as the last examination. Estimate of overall condition was performed at each weekly exam vs pretreatment exam according to treatment (cumulative frequency percentages). The methods of calculating significance were not provided and cannot be verified.

About Disability Status Scale (DSS): The DSS is a scale measured from 0 to 10 in 1-point increments, in which increasing numbers indicate increasing severity of disease. Clinically, the scale measures up to 9, and 10 represents death. The numeric difference in DSS between visits determines whether the patient is getting better (Vx – Vx-1 <0), is the same (Vx – Vx-1 = 0), or is worse (Vx – Vx-1 >0), where Vx = DSS of the current visit and Vx-1 = DSS of the previous visit. Today, the DSS has generally been replaced by the Expanded Disability Status Scale (EDSS) to assess the severity of disease.2

Overall Patient Condition

70% of patients treated with Acthar Gel showed improvement in their overall condition at 1 week compared to 49% of patients treated with placebo, a trend that continued throughout the study.1

Change in overall condition for patients treated with Acthar Gel

Disability Status Scale

At 4 weeks, the majority (65%) of patients treated with Acthar Gel improved by ≥1 Disability Status Scale (DSS) step at Week 4 compared to 48% of placebo-treated patients.1,2

Change in Disability Status Scale for patients treated with Acthar Gel

Safety and tolerability1

Side effects were observed in 43.7% of the patients treated with Acthar Gel vs 8.5% of patients receiving placebo. The 3 most frequently occurring side effects in patients treated with Acthar Gel were acne (30.9%), moon face (6.8%), and hirsutism (6.8%).

In a separate study, with a single round* of Acthar Gel treatment, 95.7% of patients achieved MS relapse resolution3

Please also see study limitations below.

This study was funded by Mallinckrodt Pharmaceuticals.

US Health Plan Study Design3,4

In this study of US health plan data, claims-based MS relapse measures were used to evaluate relapse occurrence and relapse resolution for glucocorticoids (oral or intravenous methylprednisolone [IVMP]), repository corticotropin injection (RCI; Acthar Gel in the United States), plasmapheresis (PMP), and intravenous immunoglobulin (IVIG) during index relapses; supporting evidence of IVIG’s efficacy remains limited. During the study period of January 1, 2008, to July 31, 2015, 9574 patients with MS experienced 1 or more relapses. The majority (81.4%) of these patients experienced 1 or more relapses per year. Glucocorticoids were primarily prescribed first-line but did not always provide relapse resolution. A relapse was considered “unresolved” if the next relapse occurred within 30 days.

STUDY ANALYSIS

STUDY DEFINITIONS

STUDY LIMITATIONS

With Acthar Gel, the majority of patients experienced relapse resolution with a single round* of treatment (n=232)3

RELAPSE RESOLUTION

A retrospective cohort study of administrative claims data from Humana evaluated the prevalence of MS relapse, use of treatments for MS relapse, and rate of relapse resolution for MS relapse treatments other than oral or intravenous glucocorticoids.3,4

Relapse resolution for patients treated with Acthar Gel

*Single round=single prescription (ie, no additional prescriptions/healthcare visits) needed to resolve the relapse.

Detail was suppressed per Humana privacy requirements.

HCP Resources

HEOR Humana Study

Explore MS Registry data

Indication

Acthar® Gel (repository corticotropin injection) is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

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Important Safety Information

Contraindications
  • Acthar should never be administered intravenously
  • Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
  • Acthar is contraindicated where congenital infections are suspected in infants
  • Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin

Indication

Acthar® Gel (repository corticotropin injection) is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

Warnings and Precautions
  • The adverse effects of Acthar are related primarily to its steroidogenic effects
  • Acthar may increase susceptibility to new infection or reactivation of latent infections
  • Suppression of the hypothalamic-pituitary-adrenal (HPA) axis may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g. trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA suppression after stopping treatment
  • Cushing’s syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms
  • Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Blood pressure, sodium, and potassium levels may need to be monitored
  • Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy
  • Acthar can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding
  • Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to psychosis. Existing conditions may be aggravated
  • Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis
  • Prolonged use of Acthar may produce cataracts, glaucoma, and secondary ocular infections. Monitor for signs and symptoms
  • Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity
  • There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver
  • Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients
  • Decrease in bone density may occur. Bone density should be monitored for patients on long-term therapy
  • Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Adverse Reactions
  • Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite, and weight gain
  • Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes masks other seizures, which become visible once the clinical spasms from IS resolve

Other adverse events reported are included in the full Prescribing Information.

Please see full Prescribing Information for additional Important Safety Information.

References: 1. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo—final report. Neurology. 1970;20(5):1-59. 2. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452. 3. Nazareth T, Datar M, Sheer R, Yu T-C, Schwab P. Relapse resolution and HCRU in patients with MS: a retrospective study of relapse therapy alternatives to corticosteroids. Poster presented at: 7th Joint ECTRIMS – ACTRIMS; October 25-28, 2017; Paris, France. 4. Nazareth T, Datar M, Sheer R, Yu T-C, Schwab P. MS relapse treatments and relapse resolution: retrospective study results from a US health plan. Poster presented at: 7th Joint ECTRIMS – ACTRIMS; October 25-28, 2017; Paris, France.

Indication

Acthar® Gel (repository corticotropin injection) is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

View Full

Important Safety Information

Contraindications
  • Acthar should never be administered intravenously
  • Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
  • Acthar is contraindicated where congenital infections are suspected in infants
  • Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin

Indication

Acthar® Gel (repository corticotropin injection) is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

Warnings and Precautions
  • The adverse effects of Acthar are related primarily to its steroidogenic effects
  • Acthar may increase susceptibility to new infection or reactivation of latent infections
  • Suppression of the hypothalamic-pituitary-adrenal (HPA) axis may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g. trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA suppression after stopping treatment
  • Cushing’s syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms
  • Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Blood pressure, sodium, and potassium levels may need to be monitored
  • Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy
  • Acthar can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding
  • Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to psychosis. Existing conditions may be aggravated
  • Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis
  • Prolonged use of Acthar may produce cataracts, glaucoma, and secondary ocular infections. Monitor for signs and symptoms
  • Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity
  • There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver
  • Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients
  • Decrease in bone density may occur. Bone density should be monitored for patients on long-term therapy
  • Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Adverse Reactions
  • Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite, and weight gain
  • Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes masks other seizures, which become visible once the clinical spasms from IS resolve

Other adverse events reported are included in the full Prescribing Information.

Please see full Prescribing Information for additional Important Safety Information.

References: 1. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo—final report. Neurology. 1970;20(5):1-59. 2. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452. 3. Nazareth T, Datar M, Sheer R, Yu T-C, Schwab P. Relapse resolution and HCRU in patients with MS: a retrospective study of relapse therapy alternatives to corticosteroids. Poster presented at: 7th Joint ECTRIMS – ACTRIMS; October 25-28, 2017; Paris, France. 4. Nazareth T, Datar M, Sheer R, Yu T-C, Schwab P. MS relapse treatments and relapse resolution: retrospective study results from a US health plan. Poster presented at: 7th Joint ECTRIMS – ACTRIMS; October 25-28, 2017; Paris, France.

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