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An open-label MS Registry assessed relapse recovery

IN PATIENTS WITH MS RELAPSE WHO WERE TREATED WITH ACTHAR GEL

The MS Registry Study was sponsored and funded by Mallinckrodt Pharmaceuticals.

Study Design

TREATMENT

All treatment decisions were made at the discretion of the HCP and were not mandated by the study protocol. Acthar Gel was not provided free of charge by the study sponsor; the study drug was obtained through usual commercial channels for prescription medicines.1

KEY INCLUSION CRITERIA

KEY EXCLUSION CRITERIA

ADVERSE EVENTS

Safety data (AEs and SAEs) were collected at each usual care visit and at any relapses.1

ANALYSIS

There were 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.1

*Demographics, medical history, disease-modulating therapies (prior 2 years), and concomitant medications collected at study enrollment.1

A mean of those measurements was used to compare/calculate the change in the endpoints at 2 months and 6 months.1

Patient characteristics in the MS Registry

  • Demographics and treatment patterns were based on medical charts, which were entered by site staff at baseline and usual care visits1
  • Disease-modifying therapies most often reported as being used during the study were: dimethyl fumarate, natalizumab, teriflunomide, glatiramer acetate injection, ocrelizumab, fingolimod, and interferon beta-1a1
Demographics and treatment patterns for patients treated with Acthar Gel

LIMITATIONS OF THE STUDY

Primary endpoint at 2 months and secondary endpoint at 6 months

Improvement in the primary and secondary MSIS-29v1 endpoints1,6,7

  • After treatment with Acthar Gel, mean MSIS-29v1 physical subscale scores decreased from baseline (55.69, scaled to 100) by 7.99 at 2 months (P=.0002) and 9.64 at 6 months post baseline (P<.0001)1

Improvements were clinically meaningful at 2 months and sustained at 6 months1

MSIS-29v1=Multiple Sclerosis Impact Scale Version1.

Change in MS Impact Scale score for patients treated with Acthar Gel

Secondary endpoints

Improvement in MS relapses by EDSS assessment1,8

  • Mean EDSS scores decreased from baseline (3.92, scaled to 10) by 0.37 at 2 months (P<.0001) and by 0.45 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.

Change in Expanded Disability Status Scale score for patients treated with Acthar Gel

AEs and SAEs were consistent with the published label

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

LIMITATIONS OF POST HOC ANALYSIS

  • Not a prespecified endpoint
  • Relatively small sample sizes did not allow direct statistical comparison
  • 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 U of Acthar Gel may be administered for 2 to 3 weeks. It may be necessary to taper the dose.10

Acthar Gel dosing information was collected from patient self-reports3

AE=adverse event; FDA=Food and Drug Administration; HCP=healthcare provider; ITT=intent to treat; SAE=serious adverse event.

HCP Resources

Acthar Gel MS Registry Data

SEE ACTHAR GEL EFFICACY IN OPTIC NEURITIS

Indication

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

View Full

Important Safety Information

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

Indication

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

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

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

Please see full Prescribing Information for additional Important Safety Information.

References: 1. Kaplan J, Miller T, Baker M, Due B, Zhao E. Topline results of a prospective observational registry of repository corticotropin injection for the treatment of multiple sclerosis relapse. Poster presented at: 5th Annual ACTRIMS Forum; February 27-29, 2020; West Palm Beach, FL. 2. 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. 3. Data on file: REF-MNK14130050. Mallinckrodt ARD LLC. 4. 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. 5. 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. 6. 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. 7. 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. 8. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452. 9. Busner J, Targum SD. The Clinical Global Impressions Scale: applying a research tool in clinical practice. Psychiatry (Edgemont). 2007;4(7):28-37. 10. Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

Indication

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

View Full

Important Safety Information

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

Indication

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

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

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

Please see full Prescribing Information for additional Important Safety Information.

References: 1. Kaplan J, Miller T, Baker M, Due B, Zhao E. Topline results of a prospective observational registry of repository corticotropin injection for the treatment of multiple sclerosis relapse. Poster presented at: 5th Annual ACTRIMS Forum; February 27-29, 2020; West Palm Beach, FL. 2. 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. 3. Data on file: REF-MNK14130050. Mallinckrodt ARD LLC. 4. 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. 5. 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. 6. 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. 7. 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. 8. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452. 9. Busner J, Targum SD. The Clinical Global Impressions Scale: applying a research tool in clinical practice. Psychiatry (Edgemont). 2007;4(7):28-37. 10. Acthar Gel (repository corticotropin injection) [prescribing information]. Bedminster, NJ: Mallinckrodt ARD LLC.

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