Keratitis Phase 4 study | Acthar® Gel (repository corticotropin injection)

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KERATITIS PHASE 4 STUDY Wirta et al, 2021 UVEITIS Retrospective Review Nelson et al, 2019 OPTIC NEURITIS Open-label Study Bryan et al, 2019

Wirta D, McLaurin E, Ousler G, Liu J, Kacmaz RO, Grieco J. Repository corticotropin injection (Acthar^® Gel) for refractory severe noninfectious keratitis: efficacy and safety from a phase 4, multicenter, open-label study. Ophthalmol Ther. 2021;10(4):1077-1092.

Disclosure statement: Funding to support this study was provided by Mallinckrodt Pharmaceuticals. The authors of this study have financial and/or employment relationships with Mallinckrodt Pharmaceuticals.

A Phase 4, multicenter, open-label study assessing the efficacy and safety of Acthar Gel in 36* patients with treatment-resistant, refractory, severe, non-infectious keratitis¹

Objective

To evaluate the efficacy and safety of Acthar Gel in patients with treatment-resistant, refractory, severe, non-infectious keratitis

*A target sample size of 36 patients was determined empirically. All 36 patients were included in the safety group. Efficacy endpoints were analyzed in the modified intent-to-treat (mITT) population (n=35), defined as all patients who received at least one dose of Acthar Gel and who contributed any post-baseline efficacy data to the study.

Study Design^1,2

A Phase 4, multicenter, open-label study of 36 patients with treatment-resistant, refractory, severe, non-infectious keratitis*
Patients received 80 units of Acthar Gel twice weekly for 12 weeks, followed by a taper period of 4 weeks

STUDY ASSESSMENTS¹

PRIMARY ENDPOINTS

Proportion of patients with ≥12-point improvement in the IDEEL-symptom bother score at Week 12
Proportions of patients with ≥20%, ≥30%, and ≥50% improvement in the IDEEL-symptom bother score at Week 12

IDEEL=Impact of Dry Eye on Everyday Life.

EXPLORATORY ENDPOINTS

Patient-reported outcomes

IDEEL Questionnaire
Ocular Discomfort and 4-Symptom Questionnaire
Visual analog scale (VAS)^†

Ophthalmic assessments

Corneal staining (fluorescein)
Conjunctival staining (lissamine green)
Conjunctival redness
Schirmer’s test
Visual acuity
Slit-lamp examination

^†The VAS is a validated patient-reported outcomes measure. The VAS in this study assesses various characteristic symptoms of dry eye disease.³

Acthar Gel Phase 4 severe non-infectious keratitis study results: mean
improvement in IDEEL-symptom bother score

SAFETY ENDPOINTS

Incidence and severity of ocular treatment-emergent adverse events (TEAEs), new or worsening cataracts, and mean change in intraocular pressure from baseline to Week 12

PATIENT OVERVIEW¹

Patients had severe keratitis with tough-to-treat disease and high disease activity following prior treatment

Acthar Gel Phase 4 severe non-infectious keratitis results: ≥20%, ≥30%,
and ≥50% improvement in the IDEEL-symptom bother score

LASIK=laser-assisted in situ keratomileusis.

Patient demographics and baseline characteristics

Acthar Gel Phase 4 severe non-infectious keratitis study results: visual
analog scale symptom improvement

Patients had keratitis in both eyes and experienced symptoms for 4.4 years (mean)^§ prior to treatment with Acthar Gel.

SD=standard deviation.

^‡Data based on 35 patients in the mITT population.

^§SD=5.4.

Study Limitations¹

Sample bias may exist as this was an open-label study, and patients were aware that they were receiving Acthar Gel
There was a relatively small sample size with a short treatment period of 12 weeks
The reported outcomes cannot be solely attributed to Acthar Gel. There is no control arm in this study, and other concomitant medications may not have been reported

PRIMARY ENDPOINTS¹

Improvement in IDEEL-symptom bother score by ≥12 points for 50% (n=17) of patients^† with severe keratitis at Week 12

The IDEEL Questionnaire assesses the burden of dry eye disease and was developed to meet the FDA patient-reported outcomes guidance^4,5

In a previous study, IDEEL-symptom bother baseline scores were classified as mild: 40.0 (SD=7.5), moderate: 50.6 (SD=11.0), and severe: 64.3 (SD=8.0).⁶

IDEEL=Impact of Dry Eye on Everyday Life; SD=standard deviation.

^†Data related to the IDEEL-symptom bother score were reported for 34 patients.

At least half of the patients saw improvement in their IDEEL-symptom bother score by ≥12 points¹

Mean improvements in the IDEEL-symptom bother score were clinically important at every time point

Mean change from baseline in the IDEEL-symptom bother score¹

Out of 34 patients^† at 12 weeks

MCID=minimal clinically important difference.

^†Data related to the IDEEL-symptom bother score were reported for 34 patients.

After 12 weeks of treatment with Acthar Gel¹

^‡95% CI: 33.2%, 66.8%.

^§95% CI: 27.4%, 60.8%.

^||95% CI: 2.8%, 26.5%.

EXPLORATORY ENDPOINTS¹

Complete resolution of symptoms at Week 12 was assessed by the Ocular Discomfort and 4-Symptom Questionnaire¹

Patients reported improvements at Week 12 for each domain of the Ocular Discomfort and 4-Symptom Questionnaire
20% of patients reported complete resolution in ocular discomfort at Week 12

Proportion of patients who reported complete resolution of key symptoms of severe keratitis¹

Improvements in key symptoms of severe keratitis were observed in the visual analog scale¹

The VAS is a validated patient-reported outcomes measure. The VAS in this study assesses various characteristic symptoms of dry eye disease³
From baseline to Week 12, all symptoms assessed by the mean VAS score had improved, including:

Pain
Eye discomfort
Burning/stinging

Foreign body sensation
Photophobia

Eye dryness
Itching

VAS=visual analog scale.

Improvements in ophthalmic assessments were observed as early as Week 4 and sustained through Week 12¹

Improvements in ophthalmic assessments after 4 weeks of treatment with Acthar Gel

Improvements in ophthalmic assessments after 12 weeks of treatment with Acthar Gel

NOTE: Confidence intervals only apply to observed numerical values for each assessment. They do not apply to percentage changes in improvement.

^¶95% CI: -1.5%, -0.4%.

^#95% CI: -0.9%, -0.2%.

**95% CI: -0.4%, 0.1%.

^††95% CI: 0.4%, 3.9%.

^‡‡Unanesthetized Schirmer's test to determine the amount of tears produced over 5 minutes.

^§§95% CI: -1.6%, -0.6%.

^||||95% CI: -1.2%, -0.2%.

^¶¶95% CI: -0.6%, -0.1%.

^##95% CI: -0.1%, 2.7%.

No clinically meaningful changes in visual acuity or slit-lamp examination were observed.

Safety ENDPOINTS¹

Safety data were consistent with the established safety profile of Acthar Gel

33.3% (n=12) of patients experienced ≥1 TEAE; most TEAEs were single incidences
Blurred vision and double vision were the only ocular TEAEs reported
No new safety signals were identified

No new or worsening cataracts or clinically meaningful changes in intraocular pressure were observed.

TEAE=treatment-emergent adverse event.

^†36 patients were enrolled and included in the safety population.

^‡One serious TEAE of intentional overdose with fatal outcome was reported but was not related to Acthar Gel treatment.

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Dosing recommendations

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INDICATIONS

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. Cases of anaphylaxis have been reported in the postmarketing setting. 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

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

Pregnancy

Acthar may cause fetal harm when administered to a pregnant woman

Please see full Prescribing Information for additional Important Safety Information.

REQUEST A REP

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 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.
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.
U.S. National Library of Medicine. DailyMed website. https://dailymed.nlm.nih.gov/dailymed/. Accessed March 3, 2022.

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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.
Huang YJ, 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. 2021;41(5):425-433.
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.
Benko AL, McAloose CA, Becker PM, et al. Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids. Clin Exp Immunol. 2018;192(1):68‐81.
Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies. Nat Rev Nephrol. 2011;8(2):122-128.
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References:

Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
Poola N, Due B, Wright D, Brooks LR, Zaman F. Pharmacokinetics and pharmacodynamics of repository corticotropin injection compared with synthetic ACTH1-24 depot and methylprednisolone in healthy subjects [published online ahead of print]. Clin Pharmacol Drug Dev. 2021. doi:10.1002/cpdd.1020.
Data on file: REF-03003. 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.
Data on file: REF-04768. Mallinckrodt ARD LLC
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. 2017;77(5):720-727.
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.
Wirta D, McLaurin E, Ousler G, Liu J, Kacmaz RO, Grieco J. Repository corticotropin injection (Acthar^® Gel) for refractory severe noninfectious keratitis: efficacy and safety from a phase 4, multicenter, open-label study. Ophthalmol Ther. 2021;10(4):1077-1092.

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:

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-00742. 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:

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-05336. Mallinckrodt Pharmaceuticals.
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.
Wirta D, McLaurin E, Ousler G, Liu J, Kacmaz RO, Grieco J. Repository corticotropin injection (Acthar^® Gel) for refractory severe noninfectious keratitis: efficacy and safety from a phase 4, multicenter, open-label study. Ophthalmol Ther. 2021;10(4):1077-1092.
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:

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:

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

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.

References:

Wirta D, McLaurin E, Ousler G, Liu J, Kacmaz RO, Grieco J. Repository corticotropin injection (Acthar^® Gel) for refractory severe noninfectious keratitis: efficacy and safety from a phase 4, multicenter, open-label study. Ophthalmol Ther. 2021;10(4):1077-1092.
Data on file: REF-04498. Mallinckrodt ARD LLC.
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References:

Rahaghi FF, Sweiss NJ, Saketkoo LA, et al. Management of repository corticotrophin injection therapy for pulmonary sarcoidosis: a Delphi study. Eur Respir Rev. 2020;29(155):190147. doi:10.1183/16000617.0147-2019.
Baughman RP, Scholand MB, Rahaghi FF. Clinical phenotyping: role in treatment decisions in sarcoipdosis. Eur Respir Rev. 2020;29(155):190145. doi:10.1183/16000617.0145-2019.
Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.
Rahaghi FF, Baughman RP, Saketkoo LA, et al. Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis. Eur Respir Rev. 2020;29(155):190146. doi:10.1183/16000617.0146-2019.

Keratitis

Acthar Gel may help appropriate patients with severe keratitis

A Phase 4, multicenter, open-label study assessing the efficacy and safety of Acthar Gel in 36* patients with treatment-resistant, refractory, severe, non-infectious keratitis1

Objective

To evaluate the efficacy and safety of Acthar Gel in patients with treatment-resistant, refractory, severe, non-infectious keratitis

Study Design1,2

STUDY ASSESSMENTS1

PRIMARY ENDPOINTS

EXPLORATORY ENDPOINTS

SAFETY ENDPOINTS

PATIENT OVERVIEW1

Study Limitations1

PRIMARY ENDPOINTS1

Improvement in IDEEL-symptom bother score by ≥12 points for 50% (n=17) of patients† with severe keratitis at Week 12

At least half of the patients saw improvement in their IDEEL-symptom bother score by ≥12 points1

Mean improvements in the IDEEL-symptom bother score were clinically important at every time point

Out of 34 patients† at 12 weeks

After 12 weeks of treatment with Acthar Gel1

EXPLORATORY ENDPOINTS1

Complete resolution of symptoms at Week 12 was assessed by the Ocular Discomfort and 4-Symptom Questionnaire1

Proportion of patients who reported complete resolution of key symptoms of severe keratitis1

Improvements in key symptoms of severe keratitis were observed in the visual analog scale1

Improvements in ophthalmic assessments were observed as early as Week 4 and sustained through Week 121

Improvements in ophthalmic assessments after 4 weeks of treatment with Acthar Gel

Improvements in ophthalmic assessments after 12 weeks of treatment with Acthar Gel

Safety ENDPOINTS1

Safety data were consistent with the established safety profile of Acthar Gel

Get your appropriate patients started on Acthar Gel

Dosing recommendations

INDICATIONS

Important Safety information

INDICATIONS

INDICATIONS

Important Safety information

INDICATIONS

Important Safety information

A Phase 4, multicenter, open-label study assessing the efficacy and safety of Acthar Gel in 36* patients with treatment-resistant, refractory, severe, non-infectious keratitis¹

Study Design^1,2

STUDY ASSESSMENTS¹

PATIENT OVERVIEW¹

Study Limitations¹

PRIMARY ENDPOINTS¹

Improvement in IDEEL-symptom bother score by ≥12 points for 50% (n=17) of patients^† with severe keratitis at Week 12

At least half of the patients saw improvement in their IDEEL-symptom bother score by ≥12 points¹

Out of 34 patients^† at 12 weeks

After 12 weeks of treatment with Acthar Gel¹

EXPLORATORY ENDPOINTS¹

Complete resolution of symptoms at Week 12 was assessed by the Ocular Discomfort and 4-Symptom Questionnaire¹

Proportion of patients who reported complete resolution of key symptoms of severe keratitis¹

Improvements in key symptoms of severe keratitis were observed in the visual analog scale¹

Improvements in ophthalmic assessments were observed as early as Week 4 and sustained through Week 12¹

Safety ENDPOINTS¹

Important Safety
information