A retrospective case series of 13 patients with MCD or FSGS3
Filippone et al, 2016

Overview and Study Design

A retrospective, multicenter case series of 13 patients with MCD or FSGS evaluated the efficacy and safety of Acthar. Review results from this case series now.

Treatment outcomes were defined as:

  • Complete Remission (CR)=final proteinuria measured by 24-hour urine protein <500 mg or spot urine protein <500 mg/g creatinine; >50% proteinuria reduction from baseline; and stable renal function (rise in serum creatinine <25%)
  • Partial Remission (PR)=final proteinuria in subnephrotic range (<3500 mg/24 h or <3500 mg/g of creatinine); >50% proteinuria reduction from baseline; and stable renal function (rise in serum creatinine <25%)
  • Limited Remission (LR)=>50% proteinuria reduction from baseline and stable renal function (rise in serum creatinine <25%)
  • No Response (NR)=failure to meet above criteria

Follow-up data included proteinuria and creatinine laboratory values, reported adverse events, and number of patients demonstrating study-defined treatment outcomes.

Dosing

  • The dose of Acthar ranged from 40 U QW to 80 U BIW, with most patients receiving 80 U BIW
  • Duration of therapy ranged from 1–10 months, with a median duration of 7 months (mean 5.9 months), for 11 of 13 patients who completed Acthar therapy
    • 2 patients (1 MCD, 1 FSGS) remained on ongoing therapy for total durations of 17 and 7 months, respectively
  • Follow-up period ranged from 5–17 months (median 10 months) for the 11 patients who completed Acthar therapy
  • Patients received prior renin-angiotensin system (RAS) blockade or immunosuppressive therapy (IST) at the discretion of the treating nephrologist
    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

In the 13-patient cohort, 3 patients had MCD and 10 were diagnosed with FSGS. The tables below present the baseline characteristics for the 13 patients.

  NOS=not otherwise specified.

*Prior to any therapy.

Reported as 24-hour urine or urine protein-to-creatinine ratio (UPCR) in milligrams per gram, depending on center.

11 of 13 patients (85%) received prior IST

Previous immunosuppression, used either alone or in combination, included: steroids, azathioprine, mycophenolate mofetil, cyclophosphamide, plasma exchange, abatacept, cyclosporine A, tacrolimus, rituximab, and/or pentoxifylline.

Study limitations

These results are based on a retrospective case series of 13 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.

Proteinuria was reduced in 9 of 13 (69%) MCD or FSGS patients treated with Acthar

Results*

All 3 patients with MCD and 6 of 10 patients with FSGS experienced reduction in proteinuria following Acthar treatment.

Over half of patients met remission criteria

Proteinuria was reduced in all 3 MCD patients treated with Acthar*

  Reported lab values are from follow-up unless otherwise noted.

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.

Proteinuria was reduced in 6 of 10 FSGS patients treated with Acthar*

  Coll=collapsing.

  ESRD=end-stage renal disease.

  NA=not available.

  NC=not categorized.

  NOS=not otherwise specified.

  Reported lab values are from follow-up unless otherwise noted.

Post-Acthar value is from 7-month follow-up.

Albumin/creatinine value.

§Classified as no response due to rise in creatinine.

All 3 patients with collapsing FSGS experienced reduction in proteinuria,
with 2 of 3 achieving remission criteria (1 CR, 1 PR)

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.

Safety

In the entire cohort, 5 of 13 patients reported an adverse event. Adverse events reported by the 5 patients included: weight gain (n=4), myalgias (n=2), worsening diabetes (n=2), increased skin pigmentation (n=2), hypertension (n=2), edema (n=1), and fatigue (n=1). Two patients discontinued due to side effects. The authors reported there were no cases of serious infection.

*Study limitations

Results are based on a retrospective case series of 13 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