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What is Acthar Gel?

Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides.1

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AIM FOR ANOTHER WAY

Acthar Gel is thought to modulate the immune response by1-5*:

Acthar Gel proposed MOA message

ACTIVATING

Melanocortin receptors (MCRs)

Acthar Gel proposed MOA message

INHIBITING

Production of proinflammatory cytokines

Acthar Gel proposed MOA message

MINIMIZING

IL-4/CD40L-stimulated activation and IgG production in human B cells

CD40L=cluster of differentiation 40 ligand; IgG=immunoglobulin G; IL-4=interleukin 4.

*Immunomodulatory activity may vary by condition. Each modulation may not apply to all conditions.

Watch Principal Research Pharmacologist Dale Wright, PhD, explain the proposed MOA of 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.

Melanocortin receptor engagement

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 effect2-5

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

In an in vitro study where the relative functional potency of MCRs was measured, 6% of Acthar Gel's relative functional potency occurred at MC2R. The remaining 94% occurred at the other MCRs.6

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.

 

Relative functional potency of Acthar Gel at MCRs6

Select an MCR to see where it is found in the body and some associated tissues and cells.

Receptors* y-axis

MC1R 27%

MC2R 6%

MC3R 12%

MC4R 37%

MC5R 18%

Acthar Gel
MCRs throughout the body2,7 Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors
Examples of cells that express MCRs2,8-16‡
  • Macrophages
  • Astrocytes
  • Bone cells
  • Microglia
  • Oligodendrocytes
  • Chondrocytes
  • Neutrophils
  • Schwann cells
  • Endothelial cells
  • Mast cells
  • Melanocytes
  • Podocytes
  • Lymphocytes
  • Retinal pigment epithelial cells
  • B cells
  • Adipocytes
  • Adrenal cortical cells
  • Macrophages
  • Oligodendrocytes
  • Limbic system
  • Microglia
  • Schwann cells
  • Hypothalamus
  • B cells
  • Microglia
  • Oligodendrocyte precursor cells
  • Brain stem
  • Astrocytes
  • Hypothalamus
  • Oligodendrocytes
  • Schwann cells
  • Spinal cord
  • Cortex
  • B cells
  • T cells
  • Mast cells
  • Monocytes
  • Macrophages
  • Microglia
  • Oligodendrocytes
  • Schwann cells
These examples are not an all-inclusive list.
y-axis
Receptors*

MC1R 27%

Examples of cells that express MCRs2,8-16‡

  • Macrophages
  • Astrocytes
  • Bone cells
  • Microglia
  • Oligodendrocytes
  • Chondrocytes
  • Neutrophils
  • Schwann cells
  • Endothelial cells
  • Mast cells
  • Melanocytes
  • Podocytes
  • Lymphocytes
  • Retinal pigment epithelial cells
  • B cells

These examples are not an all-inclusive list.

MC2R 6%

Examples of cells that express MCRs2,8-16‡

  • Adipocytes
  • Adrenal cortical cells

These examples are not an all-inclusive list.

MC3R 12%

Examples of cells that express MCRs2,8-16‡

  • Macrophages
  • Oligodendrocytes
  • Limbic system
  • Microglia
  • Schwann cells
  • Hypothalamus
  • B cells

These examples are not an all-inclusive list.

MC4R 37%

Examples of cells that express MCRs2,8-16‡

  • Microglia
  • Oligodendrocyte precursor cells
  • Brain stem
  • Astrocytes
  • Hypothalamus
  • Oligodendrocytes
  • Schwann cells
  • Spinal cord
  • Cortex

These examples are not an all-inclusive list.

MC5R 18%

Examples of cells that express MCRs2,8-16‡

  • B cells
  • T cells
  • Mast cells
  • Monocytes
  • Macrophages
  • Microglia
  • Oligodendrocytes
  • Schwann cells

These examples are not an all-inclusive list.

Acthar Gel
MCRs throughout the body2,7 Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors Relative functional potency of Acthar Gel: melanocortin receptors

cAMP=cyclic adenosine monophosphate; CNS=central nervous system.

*Acthar Gel was tested in vitro for its ability to increase cellular cAMP concentrations in whole cell cultures.

Acthar Gel is a partial agonist at MC5R.

 

Study Design6

Cell cultures expressing endogenous MC1R and cloned human MC2R, MC3R, MC4R, and MC5R were treated with Acthar Gel. The increase in cellular cAMP concentration 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.

EC50=half maximal effective concentration.

Cortisol induction

In a pharmacodynamic study, Acthar Gel engaged melanocortin receptors expressed on the adrenal cortex resulting in the secretion of cortisol at levels slightly above normal endogenous range, which is thought to produce an indirect anti-inflammatory effect.2,3

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.

Free cortisol response after a single therapeutic dose

Acthar Gel: free cortisol response

AUC=area under curve.

Acthar Gel AUC24=324 ± 66 hr*ng/mL.

In a pharmacodynamic study, after 5 doses, the estimated cortisol exposure of 80 units of Acthar Gel dosed twice weekly was equivalent to 8.8 mg of prednisone daily, which was 1.3 mg above normal endogenous range.2,4,5

Study design, safety findings, and study limitations2

An open-label, single-center, randomized, multiple-dose parallel group study to compare the pharmacodynamics (PD) and safety of intermittent doses of Acthar Gel to daily oral methylprednisolone (MP) in healthy subjects. Subjects between 18 and 50 years old were randomized to receive 40 or 80 units of Acthar Gel SC twice weekly for 15 days (n=12/group) or 16 mg of oral MP given once daily for 15 days (n=12), followed by a tapering regimen of 8 mg daily for 2 days, then 4 mg daily for 2 days. The most frequently reported treatment-emergent adverse events (TEAEs) that occurred in 2 or more subjects were (in decreasing order of frequency): injection site hemorrhage, headache, injection site erythema, injection site pruritus, insomnia, acne, infrequent bowel movements, and injection site pain. All TEAEs experienced during this study were considered mild in severity. As this was a healthy-subject, open-label study with no placebo control, the clinical relevance of differences in tolerability is unknown and remains to be investigated for patient populations.

SC=subcutaneous.

Direct cell modulation2

Independent of cortisol release, Acthar Gel has shown a direct effect on immune cell modulation

In an in vitro study using human B cells, Acthar Gel reduced B-cell proliferation and IgG production independent of cortisol release.

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.

Acthar Gel reduced B-cell proliferation and IgG production2

Acthar Gel: B-cell proliferation and IgG production

IgG=immunoglobulin G.

*P <.05 vs vehicle-treated group.

Study Design2

The effects of Acthar Gel on human B-lymphocyte function in vitro were evaluated using highly purified B-cell populations cultured in the absence of glucocorticoids and stimulated by recombinant IL-4 and CD40 ligand (CD40L) as specific B-cell activating signals. IgG was measured in supernatants from healthy human peripheral B cells cultured for 6 days. Percentage of cells that divided and IgG production were assessed under basal conditions (unstimulated), stimulated with IL-4/CD40L alone (vehicle), or stimulated with IL-4/CD40L plus 14.5 units/mL of Acthar Gel. Data presented were adapted from several independent studies, and the highest doses tested are shown in the graph.

CD40L=cluster of differentiation 40 ligand; IL-4=interleukin 4.

cell modulation independent of cortisol release3,4

Independent of cortisol release, Acthar Gel has shown a direct effect on immune cell modulation

In an in vitro study using human monocyte-derived macrophages (MDMs), Acthar Gel inhibited the production of pro-inflammatory cytokines IL-6 and TNF-α, indicating a potential anti-inflammatory effect independent of cortisol release.

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.

Acthar Gel inhibited the production of MDM pro-inflammatory cytokines IL-6 and TNF-α3,4

Acthar Gel: immune cell modulation

IL-6=interleukin 6; TNF-α=tumor necrosis factor alpha.

P<.0001 vs vehicle-treated group.

Study design3,4

An in vitro study to explore the direct effects of Acthar Gel on human macrophages, focusing on induction of proinflammatory mediators following lipopolysaccharide (LPS) stimulation. CD14+ monocytes were selected from human peripheral blood mononuclear cells (PBMCs). Monocytes were then treated with macrophage colony-stimulating factor (M-CSF) to generate monocyte-derived macrophages (MDMs). MDMs were stimulated with LPS and incubated for a minimum of 24 hours with Acthar Gel (7.3 units/mL) or placebo (vehicle). Highest dose tested is presented in graph. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA).

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Dosing recommendations

See dosing recommendations for Acthar Gel

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INDICATIONS & IMPORTANT SAFETY INFORMATION

Acthar® Gel is indicated for:

  • Treatment during an exacerbation or as maintenance therapy in selected cases of dermatomyositis (polymyositis)​
  • Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus​
  • Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); ankylosing spondylitis​
  • Symptomatic sarcoidosis
  • Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation​
  • Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus​
  • 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​
  • Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age

Important Safety information

Contraindications

Acthar is contraindicated:

  • For intravenous administration
  • In infants under 2 years of age who have suspected congenital infections
  • With concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar
  • 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

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 axis 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. Monitor blood pressure and sodium and potassium levels
  • 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 gastrointestinal (GI) bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain GI disorders. Monitor for signs of perforation and 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 and Acthar activity
  • There may be 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 in 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

  • Commonly reported postmarketing adverse reactions for Acthar include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia, and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased
  • The most common adverse reactions for the treatment of infantile spasms (IS) are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. Some patients with IS progress to other forms of seizures; IS sometimes masks these seizures, which may 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:

  • Data on file: REF-04586. Mallinckrodt ARD LLC.
  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • Huang JY, Galen K, Zweifel B, Brooks LR, Wright AD. Distinct binding and signaling activity of Acthar Gel compared to other melanocortin receptor agonists. J Recept Signal Transduct Res. 2020;1-9. DOI:10.1080/10799893.2020.1818094.
  • Healy LM, Jang JH, Lin YH, Rao V, Antel JP, Wright D. Melanocortin receptor mediated anti-inflammatory effect of repository corticotropin injection on human monocytederived macrophages [ECTRIMS-ACTRIMS abstract EP1481]. Mult Scler J. 2017;23(suppl 3):777.
  • 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.
  • 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.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • 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.
  • 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.
  • Healy LM, Jang JH, Lin YH, Rao V, Ante! 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.
  • 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.
  • Data on file: REF-MNK1000006114; REF-MNK1000061115; REF-MNK1000006949; REF-MNK100010998; REF-MNK1000011634; REF-MNK19972. Mallinckrodt ARD LLC.
  • Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies. Nat Rev Nephrol. 2011;8(2):122-128.
  • Lisak RP, Benjamins JA. Melanocortins, melanocortin receptors and multiple sclerosis. Brain Sci. 2017;7(104):1-18.
  • Artuc M, Grützkau A, Luger T, Henz BM. Expression of MC1- and MC5-receptors on the human mast cell line HMC-1. Ann N Y Acad Sci. 1999;885:364-367.
  • Lisak R, Bealmear B, Nedlekoska L, et al. Schwann cells express melanocortin receptor subtypes: activation by ACTH 1–39 and alpha-MSH enhances proliferation [abstract P1.430]. Neurology. 2018;90(suppl 15):1-2.
  • Cheng LB, Cheng L, Bi HE, et al. Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling. Biochem Biophys Res Commun. 2014;443(2):447-452.
  • Zhong Q, Sridhar S, Ruan L, et al. Multiple melanocortin receptors are expressed in bone cells. Bone. 2005;36(5):820-831.
  • Lindskog A, Ebefors K, Johansson ME, et al. Melanocortin 1 receptor agonists reduce proteinuria. J Am Soc Nephrol. 2010;21(8):1290-1298.
  • Mountjoy KG. Distribution and function of melanocortin receptors within the brain. Adv Exp Med Biol. 2010;681:29-48.
  • Buggy JJ. Binding of α-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway. Biochem J. 1998;331(pt 1):211-216.
  • Taylor AW, Namba K. In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (α-MSH). Immunol Cell Biol. 2001;79(4):358-367.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • Data on file: REF-MNK14314065. Mallinckrodt ARD LLC.
  • Coolens JL, Van Baelen H, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem. 1987;26(2):197-202.
  • Zoorob RJ, Cender D. A different look at corticosteroids. Am Fam Physician. 1998;58(2):443-450.
  • Data on file: REF-MNK03003. Mallinckrodt ARD LLC.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • 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.
  • 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 EP14841]. Mult Scler J. 2017;23(suppl 3):777.
  • Healy LM, Lin YH, Jang JH, Rao V, Antel JP, Wright D. Melanocortin receptor mediated anti-inflammatory effect of repository corticotropin injection on human monocyte-derived macrophages. Poster presented at: 7th Joint ECTRIMS-ACTRIMS Meeting; October 25-28, 2017; Paris, France. Poster EP1481.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • Fleischmann R, Furst DE, Connolly-Strong E, Liu J, Zhu J, Brasington R. Repository corticotropin injection for active rheumatoid arthritis despite aggressive treatment: a randomized controlled withdrawal trial. Rheumatol Ther. 2020;7(2):327-344.
  • Aggarwal R, Marder G, Koontz DC, Nandkumar P, Qi Z, Oddis CV. Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis. Ann Rheum Dis. 2018;77(5):720-727.
  • Fiechtner JJ, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial. Lupus. 2014;23(9):905-912.
  • Fiechtner JJ, Montroy T, June J. A single-site, investigator initiated open-label trial of H.P. Acthar® Gel (repository corticotropin injection) an adrenocorticotropic hormone (ACTH) analogue in subjects with moderately to severely active psoriatic arthritis (PsA). J Dermatol Res Ther. 2016;2(5):1-7.
  • Baughman RP, Barney JB, O'Hare L, Lower EE. A retrospective pilot study examining the use of Acthar gel in sarcoidosis patients. Respir Med. 2016;110:66-72.
  • Hladunewich MA, Cattran D, Beck LH, et al. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant 2014;29(8):1570-1577.
  • Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67.
  • Madan A, Mijovic-Das S, Stankovic A, Teehan G, Milward AS, Khastgir A. Acthar gel in the treatment of nephrotic syndrome: a multicenter retrospective case series. BMC Nephrol. 2016;17:37.
  • Tumlin J, Galphin C, Santos R, Rovin B. Kidney Int Rep. 2017;2(5):924-932.
  • Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011;5:147-153.
  • Filippone EJ, Dopson SJ, Rivers DM, et al. Adrenocorticotropic hormone analog use for podocytopathies. Int Med Case Rep J. 2016;9:125-133.
  • Hogan J, Bomback AS, Mehta K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013;8(12):2072-2081.

References:

  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

References:

  • Fleischmann R, Furst DE, Connolly-Strong E, Liu J, Zhu J, Brasington R. Repository corticotropin injection for active rheumatoid arthritis despite aggressive treatment: a randomized controlled withdrawal trial. Rheumatol Ther. 2020;7(2):327-344.
  • US Department of Health and Human Services. Enrichment strategies for clinical trials to support determination of effectiveness of human drugs and biological products. Guidance for industry. March 2019. https://www.fda.gov/media/121320/download. Accessed June 11, 2019.
  • Fleischmann R, Furst DE, Connolly-Strong E, Liu J, Zhu J, Brasington R. A multicenter study assessing the efficacy and safety of repository corticotropin injection in patients with persistently active rheumatoid arthritis. Poster presented at: European Congress of Rheumatology; June 12-15, 2019; Madrid, Spain.
  • Curtis JR, Yang S, Chen L, et al. Determining the minimally important difference in the clinical disease activity index for improvement and worsening in early rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2015;67(10):1345-1353.
  • Orbai AM, Bingham CO III. Patient reported outcomes in rheumatoid arthritis clinical trials. Curr Rheumatol Rep. 2015;17(4):28.

References:

  • Ho-Mahler N, Turner B, Eaddy M, Hanke ML, Nelson WW. Treatment with repository corticotropin injection in patients with rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis/polymyositis. Open Access Rheumatol. 2020;12:21-28.
  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

References:

  • Aggarwal R, Marder G, Koontz DC, Nandkumar P, Qi Z, Oddis CV. Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis. Ann Rheum Dis. 2018;77(5):720-727.

References:

  • Fiechtner JJ, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial. Lupus. 2014;23(9):905-912.

References:

  • Kaplan J, Miller T, Baker M, Due B, Zhao E. A prospective observational registry of repository corticotropin injection (Acthar® Gel) for the treatment of multiple sclerosis relapse. Front Neurol. 2020;11:598496.doi:10.3389/fneur.2020.598496.
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria. Ann Neurol. 2011;69(2):292-302.
  • Data on file: REF-MNK14130050. Mallinckrodt ARD LLC.
  • Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure. Brain. 2001;124(pt 5):962-973.
  • Jones KH, Ford DV, Jones PA, et al. The physical and psychological impact of multiple sclerosis using the MSIS-29 via the web portal of the UK MS Register. PLoS One. 2013;8(1):e5542. doi:10.1371/journal.pone.0055422.
  • Costelloe L, O'Rourke K, Kearney H, et al. The patient knows best: significant change in the physical component of the Multiple Sclerosis Impact Scale (MSIS-29 physical). J Neurol Neurosurg Psychiatry. 2007;78(8):841-844.
  • Widener GL, Allen DD. Measurement characteristics and clinical utility of the 29-item Multiple Sclerosis Impact Scale. Arch Phys Med Rehabil. 2014;95(3):593-594.
  • Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.
  • Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28-37.
  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

References:

  • Bryan MS, Sergott RC. Changes in visual acuity and retinal structures following repository corticotropin injection (RCI) therapy in patients with acute demyelinating optic neuritis: improvement in low contrast visual acuity in both affected and contralateral eyes in a single-armed open-label study. J Neurol Sci. 2019;407:116505. doi:10.1016/j.jns.2019.116505.

References:

  • Knupp KG, Coryell J, Nickels KC, et al. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol. 2016;79(3):475-484.

References:

  • Alhamad T, Manllo Dieck J, Younus U, et al. ACTH gel in resistant focal segmental glomerulosclerosis after kidney transplantation. Transplantation. 2019;103(1):202-209.
  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
  • Hladunewich MA, Cattran D, Beck LH, et al. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant. 2014;29(8):1570-1577.
  • Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67.
  • Madan A, Mijovic-Das S, Stankovic A, Teehan G, Milward AS, Khastgir A. Acthar Gel in the treatment of nephrotic syndrome: a multicenter retrospective case series. BMC Nephrol. 2016;17:37.
  • Tumlin J, Galphin C, Santos R, Rovin B. Kidney Int Rep. 2017;2(5):924-932.
  • Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011;5:147-153.
  • Filippone EJ, Dopson SJ, Rivers DM, et al. Adrenocorticotropic hormone analog use for podocytopathies. Int Med Case Rep J. 2016;9:125-133.
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