Efficacy in Rheumatoid Arthritis

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

Acthar is an adrenocorticotropic hormone (ACTH) analogue used for 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).

Gillis (2017): Acthar as Adjunctive Therapy in Patients With Rheumatoid Arthritis Who Have Failed Previous Therapies With at Least Three Different Modes of Action

Brown (2015): Acthar in Patients With Refractory Rheumatoid Arthritis: A Case Series

Gillis (2017): Acthar as Adjunctive Therapy in Patients With Rheumatoid Arthritis Who Have Failed Previous Therapies With at Least Three Different Modes of Action

Study Design1

Acthar was evaluated in an open-label, single-group study of 8 patients.1

Background

  • Despite the availability of effective treatment options, some rheumatoid arthritis (RA) patients haven’t achieved adequate disease control
  • Up to 30% of patients can experience glucocorticoid resistance
  • Between 14% and 38% of patients do not respond to first-line biologics

Methods

  • Open-label, interventional, single-group study of 8 patients with RA
  • Adult male or female patients, aged 18-80 years, with confirmed RA based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were eligible to participate in the study
  • Patients were required to have refractory disease—treated with ≥3 therapeutic agents with a different MOA for more than 3 months and still have active disease, defined as 6 tender and 6 swollen joints
  • Patients received Acthar 80 IU twice weekly via subcutaneous injection over 12 weeks
  • Patients remained on stable doses of prednisone, biologics, and/or disease-modifying antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and analgesics while being treated with Acthar
  • Primary endpoint measures included the Ritchie-Camp Articular (RCA) Index* and 20-item Health Assessment Questionnaire (HAQ) scores prior to treatment and at 2- to 4-week intervals
  • Secondary endpoint measures included acute erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels

*The Ritchie-Camp Articular Index involves a physician’s examination of the person in which 3 assessments are made. A joint count for tenderness on pressure and/or pain on motion for 68 diarthrodial joints is performed. Each joint is graded on a scale of 0 to 3, where 0=none, 1=positive response on questioning, 2=spontaneous response elicited, and 3=withdrawal by patient on examination. Joint swelling for 66 points is assessed and graded on a scale of 0 to 2, where 0=none, 1=detectable synovial thickening with loss of bony contours, and 2=bulging synovial proliferation with cystic characteristics. Joint tenderness/pain and joint swelling scores were derived by summing the 70 scores for each joint. Scores for each joint are summed to get an index score.2

Health Assessment Questionnaire assesses patient outcomes in 4 domains: disability, discomfort and pain, drug side effects, and cost. It includes 8 sections—dressing, arising, eating, walking, hygiene, reach, grip, and common activities.3

Demographics and Treatment History1

Demographic characteristics at baseline

  • 8 patients (7 women and 1 man) aged 46-801:
    • Mean (SD): 64.6 (12.1)
    • Median: 66
  • Disease duration was 9 years to 39 years
    • Mean (SD): 20.9 (11.6)
    • Median: 19.5

Treatment history of each patient prior to Acthar treatment and concomitant medications

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

DMARD=disease-modifying antirheumatic drug. SQ=subcutaneous. QD=daily.

PRN=as needed (Latin: pro re nata).

Results1

Clinical characteristics at baseline and at week 12 of Acthar treatment

CRP=C-reactive protein. DAS28=disease activity score-28. ESR=erythrocyte sedimentation rate. HAQ=health assessment questionnaire.

SD=standard deviation. VAS=visual analog scale.

  • When Acthar therapy was stopped, all improvements gained during the study period were lost by week 16

Study limitations

  • This was a small study with only 8 patients and no comparator arm
  • Sample bias may exist since this was an open-label trial and patients and physicians were aware that they were receiving Acthar
  • The results of the study cannot be solely attributable to Acthar since patients were on different medications at the start of the trial and no washout periods or standardization of concomitant medications were undertaken
  • Acthar has not been formally studied in combination with other treatments

Safety Results1

  • According to the investigators, the majority of AEs reported were mild and resolved and/or were unrelated to Acthar

Brown (2015): Acthar in Patients With Refractory Rheumatoid Arthritis: A Case Series

Study Design4

Acthar was evaluated in a retrospective case series of 5 patients with refractory RA.

Background

Despite advancements in RA treatment, patients with refractory disease could benefit from additional treatment options.

Treatment overview

  • Patients with refractory RA (defined as failure to achieve disease remission with a previous treatment) received Acthar based on its proposed mechanism of action after failing several previous therapies
  • Acthar was used to manage active disease or as a bridge therapy to manage symptoms during transition to new treatment
  • The dose of Acthar was individualized based on the disease and medical condition of the patient

Baseline assessments

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

Results4

  • Acthar improved inflammatory markers and patient-reported symptoms
  • Patients taking Acthar saw an improvement in RA symptoms, such as less pain, joint swelling, and tenderness
    • 4 patients saw improvement that continued during therapy and 1 patient had temporary improvement

Study limitations

  • Results are based on a retrospective case series of 5 patients and may not be fully representative of outcomes in the overall patient population. All patients were on other therapies. The clinical outcomes may not be solely attributable to Acthar. Acthar has not been formally studied in combination with other treatments

Treatment response and outcomes

*Inflammatory markers continued to decrease so tofacitinib 5 mg once daily was added and the Acthar dose was further reduced and then discontinued.

After this, patient experienced weight gain and elevated blood pressure so Acthar treatment was discontinued and tofacitinib once daily was added.

Change in ESR (Erythrocyte Sedimentation Rate) levels

Change in CRP (C-Reactive Protein) levels

Change in RAPID-3 (Routine Assessment of Patient Index Data with 3 Measures) score

Safety findings

  • 3 patients experienced fluctuations in blood pressure, weight, and/or glucose levels
  • 1 patient discontinued Acthar due to adverse events

*All Case 5 doses were 40 U BIW.

Maintenance dose=40 U BIW.

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