Efficacy in symptomatic sarcoidosis

Clinical experience with Acthar

A retrospective chart review of 47 patients treated with Acthar

Study Design
Study Results

Background and objective

  • Approximately half of symptomatic sarcoidosis patients will require systemic medication1
  • This data set reports on the use of Acthar treatment in patients who failed usual therapy because of progressive symptomatic disease despite immunosuppressive therapy and/or excessive toxicity with current treatment
    • The following retrospective chart review provides further information on the dosage, effectiveness, and toxicity of Acthar in treating sarcoidosis

Design

  • Uncontrolled, retrospective chart review of patients receiving at least 1 dose of Acthar therapy with at least 6 months of post-treatment follow‑up (N=47)1
  • Entry criteria included patients classified as having an incomplete response to sarcoidosis treatment on ≥1 systemic therapies prior to initiation with Acthar1
  • In this data set patients received 80 IU intramuscularly or subcutaneously twice a week1
    See the complete dosing for Acthar

Treatment duration1

Study limitations

  • Results are based on a retrospective pilot study of 47 patients and 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

Outcomes assessment

Clinical outcomes for sarcoidosis patients who were treated for ≥3 months (n=29) were determined as improved, stable, or relapsed1

Improved

Improved

  • Reduced inflammation by chest imaging or PET scanning
  • >10% improvement in forced vital capacity (FVC)
  • >50% improvement of skin lesion(s) or central nervous system (CNS) lesions on magnetic resonance imaging
  • >50% reduction in use of topical glucocorticoids for ocular disease
  • Normalization and/or 50% reduction of liver or serum calcium abnormalities

Stable

Stable

  • No clinically significant change in target organ, but reduction in dosage of glucocorticoids

Relapsed

Relapsed

  • Worsening of target organ when prednisone was reduced and patient had to be maintained on initial or higher dose of glucocorticoids

Demographics

  • Median age: 51 years; range: 20–70 years1
  • 60% Caucasian; 40% African-American1
  • All patients who were initiated on Acthar had a current or past corticosteroid treatment1

Organ involvement

  • Of 47 patients, most (81%) had lung involvement at drug initiation. Other commonly affected organs included1:
    • Central nervous system (30%)
    • Skin (21%)
    • Eye (15%)

Results

*Reduced inflammation, >10% improvement in FVC, >50% reduction in use of topical glucocorticoids, or ≥50% improvement in other organ abnormalities.

No clinically significant change in target organ, but reduction in dosage of glucocorticoids.

Worsening of target organ when prednisone was reduced and patient had to be maintained on initial or higher dose of glucocorticoids.

  • 29 of 47 patients were treated for ≥3 months; 18 were treated for <3 months1
  • A proportion of patients witnessed improvement with Acthar1:
    • Experienced objective improvement in 1 or more organs (38%)
    • Remained stable (55%)
    • Relapsed (7%)

Safety findings

18 of 47 patients discontinued treatment1 due to:

  • Death (n=2)
    • Death was attributed to the progression of sarcoidosis, not to Acthar therapy
  • Anxiety/agitation (n=3)
  • Peripheral edema (n=2)
  • Weakness (n=1)
  • Injection site allergic reaction (n=1)
  • Cost (n=4)
  • Cryptococcal infection (n=2)
  • Injection site pain (n=1)
  • Worsening disease (n=1)
  • Noncompliance (n=1)

Adverse events

  • The most commonly observed adverse events included peripheral edema or agitation (11 of 47). Six of these patients treated for ≥3 months were able to continue after the drug was reduced to 40 IU once to twice a week
  • One patient experienced skin hyperpigmentation

23 of 47 patients treated with Acthar were being treated for diabetes; 33 were on treatment for systemic hypertension1

  • Upon review, there was no significant increase of treatment for either diabetes or hypertension1

Limitations

  • These results are based on a retrospective chart review of 47 patients being treated with Acthar. There was no placebo control and the assessment of response was subjective. Results may not be fully representative of outcomes in the overall patient population. All 47 patients were receiving multiple therapies. The clinical outcomes may not be solely attributable to Acthar1

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