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Kaplan J, Miller T, Baker M, Due B, Zhao E—Frontiers in Neurology, 2020

Disclosure statement: Funding to support this study was provided by Mallinckrodt Pharmaceuticals.

A prospective open-label registry study evaluated 125 patients with MS relapse who were treated with Acthar Gel1

Objective

To characterize the patient population receiving Acthar Gel for the treatment of acute MS relapse and describe their treatment patterns, MS exacerbation recovery, and safety outcomes

Study Design1

  • Multicenter, prospective, observational registry with follow-up for 2 years, including mandated 2- and 6-month study visits post-treatment
  • Baseline measures* were taken during index exacerbation
  • Safety data (AEs and SAEs) were collected at each usual care visit and at any relapses
  • 145 patients enrolled in the registry; 82 (56.6%) completed the study
  • Effectiveness was evaluated in the ITT population, which comprised 125 patients who each received ≥1 dose of Acthar Gel and contributed to the study data
  • All treatment decisions were made at the discretion of the healthcare provider (HCP) and were not mandated by the study protocol
  • The study drug was obtained through usual commercial channels for prescription medicines

AE=adverse event; EDSS=Expanded Disability Status Scale; ITT=intent-to-treat; MSIS-29v1=Multiple Sclerosis Impact Scale Version 1; SAE=serious adverse event.

*Demographics, medical history, disease-modifying therapies (DMTs) (prior 2 years), and concomitant medications collected at study enrollment as well as MSIS-29v1 and EDSS.

Patient characteristics1

  • Demographics and treatment patterns were based on medical charts, which were entered by site staff at baseline and usual care visit
  • Approximately two-thirds of the patients reported using concomitant DMTs at some point during the study period
  • DMTs most often reported as being used during the study were: dimethyl fumarate, natalizumab, teriflunomide, glatiramer acetate, ocrelizumab, fingolimod hydrochloride, and interferon beta-1a
neuro-1

Baseline characteristics of patients who received Acthar Gel1,3

neuro-2

Approximately two-thirds of the patients reported using concomitant DMTs at some point during the study period

Acthar Gel multple sclerosis relapse study: concomitant medication

Percentage of patients that had a physician-reported history of a lack of sufficient treatment response, intolerance due to side effects, or IV access problems associated with previous treatment with high-dose glucocorticoids (eg, IVMP) for an MS relapse

IV=intravenous; IVMP=intravenous methylprednisolone.

Study Limitations3

  • Limitations of registry-based cohort studies, including limited availability of treatment data and underreporting of outcomes
  • Sample bias may exist, as this was an open-label study, and patients were aware that they were receiving Acthar Gel
  • The results cannot be solely attributed to Acthar Gel, as there was no control arm in this study, and some patients were on concurrent treatments

Some patients with MS relapses experiencing recurring disease achieved clinically meaningful improvements in the MSIS-29v1 at 2 months—and sustained them at 6 months1,4,5

Primary endpoint at 2 months and secondary endpoint at 6 months1

  • After treatment with Acthar Gel, mean MSIS-29v1 physical subscale scores decreased from baseline (55.7, scaled to 100) by 8.0 at 2 months (P =.0002) and 9.6 at 6 months post baseline (P <.0001)

Mean change from baseline in the MSIS-29v1 scale1

Acthar Gel multiple sclerosis relapse study results: mean change in MSIS-29v1 scale

A change in score of ≥8 on the physical scale is considered clinically meaningful.6,7

ITT=intent-to-treat; MSIS-29v1=Multiple Sclerosis Impact Scale Version 1; SEM=standard error of the mean.

*P<.001.

P<.01.

P<.0001.

Note: P values are based on Wilcoxon signed rank tests (ITT population) compared with baseline.

Secondary endpoints

  • Improvement in MS relapses by EDSS assessment1,8
  • Mean EDSS scores decreased from baseline (3.9, scaled to 10) by 0.4 at 2 months (P <.0001) and by 0.5 at 6 months (P <.0001)
  • Clinicians reported improvement in CGI-I scores in the majority of patients1,9
  • CGI-I scores indicated improvement in 63.4% of patients (45/71, P <.0001) at 2 months and 61.4% of patients (35/57, P <.0001) at 6 months

CGI-I=Clinical Global Impressions-Improvement; EDSS=Expanded Disability Status Scale.

Mean change from baseline in the EDSS scale1

Acthar Gel multiple sclerosis relapse study results: mean change in EDSS score

Mean scores decreased at 2 and 6 months from a baseline EDSS score of 3.9.

P <.0001.

Note: P values are based on Wilcoxon signed rank tests (ITT population) compared with baseline.

POST HOC ANALYSIS

In a post hoc analysis evaluating the number of doses, greater improvements in MSIS-29v1 and EDSS were observed in some patients taking >5 doses of Acthar Gel1

  • Improvements at Month 2 were sustained at Month 6

Limitations of post hoc analysis1,3

  • Not a prespecified endpoint
  • No direct statistical comparison was made
  • Limitations of registry-based cohort studies, including limited availability of treatment data and underreporting of outcomes
  • It may not be possible to extrapolate the results to a broader population
  • Based on patient self-reported data

As approved by the FDA, daily intramuscular or subcutaneous doses of 80 to 120 units of Acthar Gel may be administered for 2 to 3 weeks. It may be necessary to taper the dose.10

Mean change from baseline in the MSIS-29v1 physical subscale, by number of doses administered1

Acthar Gel multiple sclerosis relapse study results: MSIS-19v1 physical subscale score

*P <.001.

P <.01.

P <.0001.

§P <.05.

Note: P values are based on Wilcoxon signed rank tests (ITT population) compared with baseline.

Mean change from baseline in the EDSS scale, by number of doses administered1

Acthar Gel multiple sclerosis relapse study results: mean change in EDSS score

P <.01.

P <.0001.

§P <.05.

Note: P values are based on Wilcoxon signed rank tests (ITT population) compared with baseline.

Acthar Gel dosing information was collected from patient self-reports.3

Safety ENDPOINTS1

AEs and SAEs were consistent with the published label

  • A total of 83 AEs were reported by (28.0%, n=35) patients1
  • A total of 16 SAEs were reported by (8.8%, n=11) patients1
  • Fewer than 5% of patients had3:
  • Treatment-related AEs (4.8%, n=6)
  • Severe AEs (4.0%, n=5); none were treatment-related
  • AEs leading to treatment withdrawal (1.6%, n=2)
  • The most common AEs were MS relapse (4.0%, n=5), urinary tract infection (3.2%, n=4), peripheral edema (2.4%, n=3), nasopharyngitis (2.4%, n=3), cellulitis (1.6%, n=2), asthenia (1.6%, n=2), back pain (1.6%, n=2), dyspnea (1.6%, n=2), fall (1.6%, n=2), headache (1.6%, n=2), nausea (1.6%, n=2), and rash (1.6%, n=2)1
  • The most common SAEs were MS relapse (4.0%, n=5), asthenia (1.6%, n=2), and urinary tract infection (1.6%, n=2)1
  • No deaths were reported

AE=adverse event; SAE=serious adverse event.

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Dosing recommendations

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INDICATIONS

Acthar® Gel is indicated for:

  • Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
  • Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
  • • 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

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

INDICATIONS

Acthar® Gel is indicated for:

  • Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
  • Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
  • 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
  • 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
  • Symptomatic sarcoidosis
  • Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
  • Treatment during an exacerbation or as maintenance therapy in selected cases of dermatomyositis (polymyositis)
  • 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

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.
  • 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:

  • 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.

References:

  • Baughman RP, Sweiss N, Keijsers R, et al. Repository corticotropin for chronic pulmonary sarcoidosis. Lung. 2017;195(3):313-322.

References:

  • Data on file: REF-04586. 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.
  • Chopra I, Qin Y, Kranyak J, et al. Repository corticotropin injection in patients with advanced symptomatic sarcoidosis: retrospective analysis of medical records. Ther Adv Respir Dis. 2019;13:1753466619888127. doi:10.1177/1753466619888127.
  • Data on file: REF-MNK14084113. Mallinckrodt ARD LLC.
  • Zand L, Canetta P, Lafayette R, et al. An open-label pilot study of adrenocorticotrophic hormone in the treatment of IgA nephropathy at high risk of progression. Kidney Int Rep. 2020;5(1):58-65.
  • 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.

References:

  • 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(1):37. doi:10.1186/s12882-016-0241-7.
  • Data on file: REF-ARDUS/01-03/0917/0002. Mallinckrodt ARD LLC.
  • Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. Clinical practice guideline for glomerulonephritis. Kidney Int Suppl. 2012;2(2):139-274.

References:

  • Zand L, Canetta P, Lafayette R, et al. An open-label pilot study of adrenocorticotrophic hormone in the treatment of lgA nephropathy at high risk of progression. Kidney Int Rep. 2020;5(1):58-65.
  • Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

References:

  • Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996;97(3):375-379.

References:

  • Data on file: REF-MNK14084113. 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:

  • 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.
  • Schmitt J, Wozel G. The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis. Dermatology. 2005;210(3):194-199.

References:

  • Chopra I, Qin Y, Kranyak J, et al. Repository corticotropin injection in patients with advanced symptomatic sarcoidosis: retrospective analysis of medical records. Ther Adv Respir Dis. 2019;13:1753466619888127. doi:10.1177/1753466619888127.

References:

  • Tumlin J, Galphin C, Santos R, Rovin B. Kidney Int Rep. 2017;2(5):924-932.

References:

  • Nelson WW, Lima AF, Kranyak J, et al. Retrospective medical record review to describe use of repository corticotropin injection among patients with uveitis in the United States. J Ocul Pharmacol Ther. 2019;35(3):182-188.