A retrospective case series of 21 patients with nephrotic syndrome of various etiologies7
Bomback et al, 2011

Overview and Study Design

A retrospective analysis evaluated the efficacy and safety of Acthar in all known cases of idiopathic, nondiabetic syndrome (n=21) treated outside the research setting for a minimum of 6 months.

Outcome measures included the number of patients achieving remission defined by changes in estimated glomerular filtration rate (eGFR), as follows:

  • Complete remission (stable or improved renal function with final proteinuria falling to <500 mg/day)
  • Partial remission (stable or improved renal function with ≥50% reduction in proteinuria and final proteinuria 500–3500 mg/day)
  • No response (failure to meet the above criteria)

Treatment regimens were not uniform; the most common treatment regimen was 80 IU BIW for 6 months. Duration of treatment ranged from 1 to 12 months, and follow-up time ranged from 6 to 14 months.

Dosing of Acthar (as stated in Prescribing Information): Dosage and frequency of Acthar should be individualized according to the medical condition, severity of the disease, and initial response of the patient.

  • The usual dose of Acthar is 40 to 80 units given intramuscularly or subcutaneously every 24 to 72 hours

Patient Baseline Characteristics

*Previous immunosuppression, used either alone or in combination, included: MMF, CNI, steroids, CTX, and/or rituximab.

  MMF=mycophenolate mofetil.

  CNI=calcineurin inhibitors.

  CTX=cyclophosphamide.

11 of 21 patients with nephrotic syndrome reached complete or partial remission with Acthar

Acthar reduced proteinuria in 10 of 11 patients with iMN

4 of 11 patients in the iMN group experienced adverse events.

  • Patients 4 and 11 reported hyperglycemia and Patient 6 reported weight gain
  • Patient 7 demonstrated evidence of bone demineralization

Acthar reduced proteinuria in 6 of 10 patients with nephrotic syndrome of various etiologies

*Experienced reduction in proteinuria to remission levels, but eGFR declined >25% and did not meet response criteria.

Proteinuria dropped from 1340 mg/day to 420 mg/day; however, therapy was discontinued due to weight gain and proteinuria rebounded to 2290 mg/day.

In the remaining 10 patients with nephrotic syndrome of various etiologies, 2 experienced adverse events:

  • Patient 19 reported weight gain
  • 1 month after treatment initiation, Patient 20 developed acute renal failure; following drug discontinuation, resulting creatinine ranged from 5.0 to 6.0 mg/dL

The authors reported there were no cases of severe infection.

Study limitations

These results are based on a retrospective case series of 21 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.
Acthar is used to induce a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.

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

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-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.

Indication

H.P. Acthar® Gel (repository corticotropin injection) is indicated to induce a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.

References