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There’s only one Acthar Gel

MS RELAPSE AND ACTHAR GEL

While the exact mechanism of action of Acthar Gel is not fully understood, further investigation is being conducted. This information is based on nonclinical and pharmacodynamic data, and the relationship to clinical benefit is unknown.

Understanding the Potential MOA of Acthar Gel

Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides.1 Acthar Gel engages melanocortin receptors (MCRs) expressed on immune cells and other tissues throughout the body and is thought to produce both an indirect anti-inflammatory effect and a direct cell effect.2-6

The potential role of MCRs in MS relapse

There are 5 MCR subtypes (MC1R to MC5R) that are expressed in various tissues throughout the body.2

MCRs are involved in anti-inflammatory and immunomodulatory functions2,7,8

Some of these MCRs may be implicated in MS relapse.2,7,8

Acthar Gel and melanocortin receptors that may be involved in MS relapse

MCR engagement

In the body, MC2Rs are primarily expressed on the adrenal cortex and the engagement of these receptors leads to the production of cortisol. The other MCRs are found on immune and other cells throughout the body. They play a key role in regulating inflammation and other cellular functions.2

Relative functional potency of Acthar Gel: engagement with melanocortin receptors

49%

of Acthar Gel’s functional potency occurred at MCRs expressed on central nervous system cells, which may lead to direct cell effects.2,3

STUDY DESIGN3,9

Cell cultures expressing endogenous MC1R and cloned human MC2R, MC3R, MC4R, and MC5R were treated with Acthar Gel. The increase in cellular cAMP concentrations was assayed. Agonist activity was determined using nonlinear regression analysis of the concentration response curves. Relative functional potency was determined by calculating the log of each EC50 value, summing EC50 values, and determining the percentage of the total for each receptor. Receptor densities and the induction of cAMP are assumed to be equivalent for all receptors.

cAMP=cyclic adenosine monophosphate; EC50=half maximal effective concentration.

LEARN ABOUT CORTISOL RELEASE AND CELL MODULATION

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. Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC. 2. Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010;10:1840-1853. doi:10.1100/tsw.2010.173. 3. Wright D, Fitch R. Repository corticotropin injection (H.P. Acthar Gel) enhances remyelination after cuprizone-induced demyelination [CMSC abstract NDM04]. Int J MS Care. 2019;21(suppl 1):61-62. 4. Olsen NJ, Decker DA, Higgins P, et al. Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro. Arthritis Res Ther. 2015;17:300. doi:10.1186/s13075-015-0823-y. 5. Healy LM, Jang JH, Lin YH, Rao V, Antel JP, Wright D. Melanocortin receptor mediated anti-inflammatory effect of repository corticotropin injection on human monocyte-derived macrophages [ECTRIMS-ACTRIMS abstract EP1481]. Mult Scler J. 2017;23(suppl 3):777. 6. Wright D, Zweifel B, Sharma P, Galen K, Fitch R. Reduced steroidogenic activity of repository corticotropin injection induces a distinct cytokine response following T cell activation in vivo. [EULAR abstract AB0082]. Ann Rheum Dis. 2019b;78(suppl 2):1504. 7. Berkovich R, Agius MA. Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(2):83-96. 8. Ross AP, Ben-Zacharia A, Harris C, Smrtka J. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Front Neurol. 2013;4:21. 9. Data on file: REF-MNK1000006114; REF-MNK1000061115; REF-MNK1000006949; REF-MNK100010998; REF-MNK1000011634; REF-MNK19972. Mallinckrodt ARD LLC.

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. Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC. 2. Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010;10:1840-1853. doi:10.1100/tsw.2010.173. 3. Wright D, Fitch R. Repository corticotropin injection (H.P. Acthar Gel) enhances remyelination after cuprizone-induced demyelination [CMSC abstract NDM04]. Int J MS Care. 2019;21(suppl 1):61-62. 4. Olsen NJ, Decker DA, Higgins P, et al. Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro. Arthritis Res Ther. 2015;17:300. doi:10.1186/s13075-015-0823-y. 5. Healy LM, Jang JH, Lin YH, Rao V, Antel JP, Wright D. Melanocortin receptor mediated anti-inflammatory effect of repository corticotropin injection on human monocyte-derived macrophages [ECTRIMS-ACTRIMS abstract EP1481]. Mult Scler J. 2017;23(suppl 3):777. 6. Wright D, Zweifel B, Sharma P, Galen K, Fitch R. Reduced steroidogenic activity of repository corticotropin injection induces a distinct cytokine response following T cell activation in vivo. [EULAR abstract AB0082]. Ann Rheum Dis. 2019b;78(suppl 2):1504. 7. Berkovich R, Agius MA. Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(2):83-96. 8. Ross AP, Ben-Zacharia A, Harris C, Smrtka J. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Front Neurol. 2013;4:21. 9. Data on file: REF-MNK1000006114; REF-MNK1000061115; REF-MNK1000006949; REF-MNK100010998; REF-MNK1000011634; REF-MNK19972. Mallinckrodt ARD LLC.

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