A combined prospective trial and retrospective review of 24 patients with proteinuria due to FSGS4
Hogan et al, 2013

Overview

A combined prospective trial and retrospective review assessed the use of Acthar in 24 patients with biopsy-proven FSGS previously treated with other therapies.

Primary outcome measures included:

  • Patients achieving complete remission (CR=stable or improved renal function with final proteinuria falling to <500 mg/g by spot UPCR or 24-hour urine protein measurement), partial remission (PR=stable or improved renal function with ≥50% reduction in proteinuria and final proteinuria 500–3500 mg/g), or treatment failure (NR)

Additional measures were:

  • Changes in blood pressure, body mass index, serum albumin, and cholesterol levels
  • Documented adverse events recorded during therapy for patients evaluated prospectively and from chart reviews for those studied retrospectively

Study Design

Patients were studied prospectively at Stanford University and Columbia University medical centers (n=16), previously described* (n=4), and evaluated retrospectively on the basis of chart reviews (n=4) between 2009 and 2012.

In the 5 patients treated at the discretion of a physician, the median regimen was 80 IU SC twice weekly. The duration of therapy ranged from 12 to 56 weeks, and the mean follow-up time after Acthar completion was 48 ± 29 weeks.

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

*Patients were previously described with shorter-term results in Bomback et al, 2011 and Bomback et al, 2012.

Patient Baseline Characteristics

IQR=interquartile range.

*Patients may have been previously treated with 1 or more of the following: steroids, MMF, tacrolimus, cyclosporine, and/or CTX.

  MMF=mycophenolate mofetil.

  CTX=cyclophosphamide.

7 of 24 patients with FSGS achieved remission with Acthar (2 CR, 5 PR)

Acthar reduced proteinuria in more than half of all patients (14/24).

  Adapted from Hogan et al, 2013.

Changes in other laboratory values including creatinine and serum albumin were also assessed in the study.

Acthar is indicated to reduce proteinuria of nephrotic syndrome. The impact of Acthar on other relevant lab values has not been more formally assessed and is included here for clinical context only.

Study limitations

These data are subject to limitations. The data combine retrospective observational data with prospective data of patients who were not randomly assigned to therapy. There was no comparison group for interpretation of safety and efficacy findings with Acthar. Most patients were on multiple therapies during Acthar treatment, and the clinical outcomes may not be solely attributable to Acthar.

Safety

  • 52 adverse events were reported in 21 of 24 patients on Acthar
    • 23 corticosteroid-like adverse events
      • The most common included swelling, edema, volume overload, weight gain, increased energy, mood alteration, upper respiratory tract infection symptoms, muscle cramps, elevated blood pressure, acne, dyspepsia, acute kidney infection, pain at injection site, tanning of skin, and rash
  • 1 episode of new-onset diabetes was reported that resolved following cessation of Acthar
  • 5 infections were reported (1 case of pneumonia, 4 cases of upper respiratory tract infection)
  • 4 patients were hospitalized during treatment
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