Clinical experience with Acthar in the treatment of systemic lupus erythematosus (SLE)

Acthar was evaluated in a prospective, single-site, open-label, non–placebo-controlled study of 10 patients1*

  • The primary endpoint was to evaluate whether the addition of Acthar to standard treatment for SLE reduced the intensity of flares as measured by changes in SLEDAI-2K scores from baseline at Day 28
  • All patients had moderately to severely active disease and also met ACR criteria for SLE flare, including:
    • Antinuclear antibody (ANA) positivity
    • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6
    • At least 1 British Isles Lupus Assessment Group Index (BILAG) A or 2 B organ system scores
    • Physician Global Assessment score ≥1 on a 0-3 visual analog scale (VAS)
  • All 10 patients had to have received either a stable dose of prednisone (or equivalent) ≤20 mg/day for at least 4 weeks or 8 weeks of a commonly used immunosuppressive or antimalarial treatment for SLE. At baseline, patients were receiving one or more of the following:
    • Corticosteroids
    • Methotrexate
    • NSAIDs
    • Hydroxychloroquine
    • Belimumab

*Results are based on a prospective, single-site, open-label, non–placebo-controlled study of 10 patients.

  • This study may not be fully representative of outcomes in the overall patient population
  • Most patients were on multiple therapies
  • The clinical outcomes may not be solely attributable to Acthar
  • Acthar has not been formally studied in combination with other commonly used therapies for SLE

Treatment with Acthar1

  • Patients self-administered 1 mL (80 U) Acthar daily for 10 days, in addition to their existing regimen, with an optional 5-day extension for nonresponders (SLEDAI-2K >6)
  • Patients were assessed weekly for 28 days and could report adverse events at any time during the study

Reduction in SLE disease activity (N=10)

Acthar provided statistically significant reductions in SLEDAI-2K scores at Day 281

SLEDAI-2K scores were calculated for each patient based on the presence or absence of organ manifestations in the previous 10 days. Responses for each organ manifestation were weighted and totaled into the final score, ranging from 0 (inactive disease) to 105.

Acthar improved the following secondary endpoints at 28 days1

  • Physician Global Assessment
  • Patient Global Assessment
  • Erythrocyte sedimentation rate (ESR)
  • Lupus Quality of Life (Lupus QoL) scale
  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale

Safety findings in the prospective, open-label trial (N=10)1*

  • One patient discontinued treatment at 7 days due to bilateral edema in the legs/ankles
  • One patient reported a sinus infection that resolved with antibiotic treatment

*Results are based on a prospective, single-site, open-label, non–placebo-controlled study of 10 patients.

  • This study may not be fully representative of outcomes in the overall patient population
  • Most patients were on multiple therapies
  • The clinical outcomes may not be solely attributable to Acthar
  • Acthar has not been formally studied in combination with other commonly used therapies for SLE

Common adverse reactions for H.P. Acthar Gel 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.

This study was Mallinckrodt-funded.

Review demonstrated safety profile and findings based upon the prospective, open-label pilot study. Learn more

Important Safety Information

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Contraindications

  • Acthar should never be administered intravenously
  • Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar

Important Safety Information

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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 origins

Warning 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-axis (HPA) 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, and 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 mask 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.

Indications

H.P. Acthar® Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for:

  • 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 systemic dermatomyositis (polymyositis)
  • Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
  • Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in psoriatic arthritis
  • The treatment of symptomatic sarcoidosis
References