Efficacy in Dermatomyositis
and Polymyositis

Use the links below to browse through clinical experience with Acthar.

Acthar is indicated for use during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis).

Aggarwal (2016): Open-label, Prospective Study (N=11)

Levine Interim Analysis (2016): Acthar in Dermatomyositis and Polymyositis Treatment (ADAPT) Registry (N=24)

Patel (2016): Retrospective Case Series (N=4)

Levine (2012): Retrospective Case Series (N=5)

Acthar Was Evaluated in an Open-Label, Prospective Study of 11 Patients With DM/PM*

Study Design1

  • A 24-week proof-of-concept study of 11 adults with refractory and active dermatomyositis (DM) and polymyositis (PM)*
    • Patients had refractory and active disease defined as failing an adequate glucocorticoid trial (≥2 months of high doses [0.75 to 1 mg/kg] or intolerance to such therapy) and/or ≥1 conventional immunosuppressive agent
    • Active disease defined as:
      • Baseline Manual Muscle Testing (MMT-8) score ≤125/150 and ≥2 additional abnormal core set measures (CSMs), or
      • DM with cutaneous 10-cm Visual Analogue Scale (VAS) score ≥3 cm on the Myositis Disease Activity Assessment Tool (MDAAT) and at least 3 other abnormal CSMs (excluding the MMT-8)
  • All patients received the same dose of Acthar, 80 U twice weekly, for 24 weeks

Objective

  • To evaluate the efficacy, safety, tolerability, and steroid-sparing effect of Acthar in patients with refractory DM/PM

Patient overview

Outcome Measures1

Primary endpoint

  • Three of any of the 6 CSMs improved by ≥20%, with no more than 2 CSMs worsening by ≥25%, based on International Myositis Assessment & Clinical Studies Group (IMACS) definition of improvement (DOI)
    • Worsening measure could not include the MMT
  • Primary endpoint was also separately evaluated on a subset of patients with severe muscle weakness (≤125/150 of MMT at baseline), as well as moderate to severe cutaneous DM rashes (≥2.5/10 of cutaneous VAS score at baseline)

Secondary endpoints

  • Median change in 6 individual CSMs:
    • MMT
    • Physician global assessment of change (MD global)
    • Health Assessment Questionnaire (HAQ)
    • Patient global
    • Muscle enzyme
    • Extra-muscular global
  • Median time to DOI from baseline
  • 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria
  • Mean change in glucocorticoid dose at 24 weeks
  • Secondary safety and tolerability endpoints were measured by frequency and type of adverse and severe adverse events

CSM: Core Set Measure

IMACS has developed a set of Core Set Domains and Measures to help clearly assess disease activity. IMACS recommends including these CSMs in trials and studies that assess disease activity in patients with myositis.2

*Ten of the 11 enrolled patients completed the study. One patient dropped out due to heart block unrelated to the study drug and was not included in the analysis, as he did not complete the minimum 8 weeks of the study drug required for outcome assessment as per study protocol.

Concomitant immunosuppressive agents or glucocorticoids were allowed as long as patients were on these therapies for ≥8 weeks (and ≥4 weeks for glucocorticoids) and on a stable dose for ≥4 weeks and ≥2 weeks, respectively, prior to the start of the trial.

Results

Primary endpoint1

70% of Patients Met the DOI After Treatment With Acthar

  • Seven out of 10 patients completing the study met the IMACS DOI by a median of 8 weeks (interquartile range [IQR]=4 to 20 weeks)
  • DM and PM patients did not differ in their response to treatment

DOI=definition of improvement.

Study limitations

Results are based on 10 patients who completed the study. This study may not be fully representative of outcomes in the overall patient population. All patients were on multiple therapies; therefore, the clinical outcomes may not be solely attributable to Acthar. Acthar has not been formally studied in combination with other treatments.

Secondary endpoints1

  • 90% of patients met the secondary outcome measure of minimal improvement using the new 2016 American College of Rheumatology/European League Against Rheumatism myositis response criteria, but 2 patients had significant worsening before the 24-week period
  • Median interquartile range total improvement score* was 52.5 (30 to 65) at 24 weeks with 40%, 30%, and 20% of patients achieving minimal, moderate, and major improvement, respectively

Median changes in all CSMs for all 10 evaluated patients1

CSM=core set measure. HAQ-DI=Health Assessment Questionnaire Disability Index. MD global=physician global disease activity. MMT=Manual Muscle Testing.

Start and end values for severe MMT, rash, and muscle enzyme were not reported.

*Metric derived from the 2016 ACR/EULAR myositis response criteria, which corresponds to magnitude of improvement.

All patients in study decreased or discontinued prednisone doses by week 241

  • All patients decreased prednisone doses by week 24
  • 50% of patients discontinued prednisone completely by week 24

Prednisone dose reduction by patient

Safety findings1

Many of the observed adverse events were similar to those seen with glucocorticoids. Other factors typically associated with high-steroid doses given for an extended period, such as significant weight gain, diabetes, or Cushingoid features, were not observed.

Summary of adverse events

*Total left hip arthroplasty.

Transvenous pacemaker insertion.

Levine Interim Analysis (2016): Acthar in Dermatomyositis and Polymyositis Treatment (ADAPT) Registry (N=24)

Study Design1

Acthar was evaluated in a multicenter retrospective registry (an observational study) of patients diagnosed with dermatomyositis (DM) and polymyositis (PM) who were refractory to first- and second-line therapies.

Primary objective:

  • Determine the effect of Acthar on clinical outcomes

Secondary objective:

  • Determine if distinct subgroups of patients, as defined by myopathology or autoantibody status, have different responses to Acthar treatment

Patient variables assessed for association with responsiveness to Acthar treatment included:

  • DM/PM diagnosis
  • Sex
  • Age
  • Presence of autoantibodies at baseline
  • Extramuscular symptoms (rash) at baseline
  • Administration of concomitant medications

Patient overview

  • 24 patients with DM (n=7) or PM (n=17) (biopsy confirmed)
  • 6 patients were male and 18 were female
  • The average age of the patients was 55 years (range: 26-77 years)
  • Patients were refractory to some combination of corticosteroids, immunosuppressants, rituximab, and intravenous immunoglobulin (IVIG)
  • Patients received an average of 3.4 medications over an average of 3.2 years before beginning the Acthar regimen

Additional characteristics

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

SD=standard deviation.

*Disease activity defined as elevated CPK or a decline in manual muscle testing (MMT) within 90 days prior to initiation of Acthar treatment.

Treatment overview

  • Acthar was administered via SC injection
    • 80 IU 2x/week (n=22)
    • 40 IU 2x/week (n=1)
    • 80 IU 1x/week (n=1)
  • Treatment ranged from 2 to 18 months, with a median of 6 months
  • 22 of 24 patients were treated concomitantly with other medications

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

Initial dosing was 80 IU twice weekly via SC injection. Physicians adjusted doses at their discretion based on disease severity, concomitant health issues, and response to therapy.

Treatment Response

Primary objective

58% of patients had clinically significant improvement with Acthar treatment (n=14)1

There was no association between responsiveness and condition.

  • 57% (4/7) of DM patients responded
  • 59% (10/17) of PM patients responded

Outcomes were determined by an independent review of the prescribing physician’s notes, clinical parameters, and laboratory data for each patient. Patient laboratory results included myositis-specific antibodies, glycated hemoglobin (HbA1c), and creatine phosphokinase (CPK).

Study limitations1

  • These results are based on an interim observational study and may not be fully representative of outcomes in the overall patient population. 22 patients were on multiple therapies. The clinical outcomes may not be solely attributable to Acthar
  • While this is the largest observational trial to date, the sample size (N=24) was small. Treatment and assessment of a larger population for a longer time period may provide further insight into predictors of responsiveness
  • The population in this study is primarily female and therefore it cannot be determined if gender may have a significant influence on the efficacy of Acthar in DM/PM patients
  • This study is uncontrolled and, as such, all patients were not receiving a uniform standard of care. Patients received different classes of medications and combinations of these medications at the time of intervention with Acthar, without a washout period or standardization of their concomitant treatments. No patient cohort was established to receive a standard of care for DM/PM without concomitant Acthar for comparison

Secondary objective

Elevated CPK correlated to response to Acthar treatment1

Response to Acthar treatment frequently occurred in patients with CPK levels ≥200 IU/L at baseline (P<0.001).

The median CPK at baseline for patients who responded to Acthar was 616 (range: 84-1764) compared to 105 (range: 53-460) for patients who did not respond to Acthar (P=0.0047).

NS=variable not significantly associated with response to Acthar treatment.

Outcomes were determined by an independent review of the prescribing physician’s notes, clinical parameters, and laboratory data for each patient. Patient laboratory results included myositis-specific antibodies, glycated hemoglobin (HbA1c), and creatine phosphokinase (CPK)

Disease activity correlated with response to Acthar treatment1

Disease activity defined as elevated CPK or a decline in MMT within 90 days before initiation of Acthar.

NS=variable not significantly associated with response to Acthar treatment.

Relationship between treatment and response1

  • Patients who responded had a higher mean duration of treatment (9.7 months) vs nonresponders, whose mean treatment duration was 3.5 months (P<0.0001)
  • Acthar treatments of longer duration also correlated with a larger percent change reduction in CPK levels from baseline (P=0.0123)

Safety findings

  • 41.7% of patients reported mild to moderate adverse events (AEs)1
  • No patient discontinued treatment exclusively due to AEs1
    • Patients who chose to discontinue experienced AEs and did not achieve clinical response

Reported adverse events in patients with DM or PM treated with acthar (N=24)1

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.2

Patel (2016): Retrospective Case Series (N=4)

Study Design3

Acthar was evaluated in a retrospective case series of 4 patients with dermatomyositis and polymyositis:

Treatment overview

  • 4 patients with DM (n=2) or PM (n=2) treated with Acthar 80 IU 2x/wk SC in conjunction with other therapies
    • All patients had received ≥2 previous treatments with incomplete response

Summary of baseline characteristics

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

Results

Summary results3

  • 3 patients improved after treatment with Acthar; 1 patient did not respond
  • Acthar did not exacerbate any comorbidity and no significant changes in blood pressure, weight, or glycemic control were observed

Study limitations

These results are based on a retrospective 4-patient case series and may not be fully representative of outcomes in the overall patient population. All 4 patients were on multiple therapies. The clinical outcomes may not be solely attributable to Acthar.3

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.2

Clinical assessments for each case before and after treatment with Acthar3

CK=creatine kinase.

*Measured via manual muscle testing and converted to a generalized scale (0, 1, 2=severe; 3=moderate; 4=mild; 5=normal).

In one dermatomyositis patient, rash mostly resolved and a flare-up of the erythematous rash after sun exposure resolved.
In the other dermatomyositis patient, rash remained active but did not worsen.

Levine (2012): Retrospective Case Series (N=5)

Study Design4

Methods

  • At the time Acthar treatment was initiated, all patients were experiencing ongoing disease exacerbations and demonstrated a decrease in muscle strength
  • All 5 patients were also being treated with stable doses of at least 1 other commonly used therapy for dermatomyositis or polymyositis
    • These medications had been prescribed for at least 60 days before and were maintained during and after Acthar treatment

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

Treatment with Acthar

  • 4 patients received 80 units (1 mL) 2x/week for 12 weeks
  • 1 patient received 80 units 1x/week for 12 weeks

Results

5 of 5 patients treated with Acthar demonstrated improvement in MMT scores4

  • Manual muscle testing (MMT) was performed to assess muscle strength at baseline and 12 weeks

MMT was performed using the Medical Research Council scale (1-5). Patients were treated for 12 weeks and MMT was performed at different times of assessment. All 5 patients were on stable doses of at least 1 commonly used therapy for dermatomyositis or polymyositis.

Study limitations

These results are based on a retrospective 5-patient case series and may not be fully representative of outcomes in the overall patient population. All 5 patients were on multiple therapies. The clinical outcomes may not be solely attributable to Acthar.4

For more details, review a dermatomyositis case study and a polymyositis case study from this series.

Safety findings

  • Patients receiving Acthar were examined for significant side effects, including: hyperglycemia, diabetic ketoacidosis, and hyperosmolar states4
  • No significant adverse events as defined in the study methods were reported by the investigator in any of the 5 patients4

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.2

The safety profile of Acthar has been demonstrated over many years. 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

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.

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