Potential MOA

Acthar Gel engages melanocortin receptors (MCRs) expressed on immune cells and other tissues throughout the body^1-5

Melanocortin peptides are molecules produced in response to inflammation and can contribute to controlling and balancing the inflammatory process by exerting anti-inflammatory actions^6,7

Melanocortin peptides bind to and may activate melanocortin receptors on various immune cells and structural cells, including T cells, B cells, and other antigen-presenting cells^1,3,6-21

T cells

Reduction in proinflammatory cytokines and mediators (eg, TNF-α and TNF-α–induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB])
Increase in anti-inflammatory cytokines and mediators
Increased conversion of T-helper cells to T-regulator cells

T cells

Reduction in proinflammatory cytokines and mediators (eg, TNF-α and TNF-α–induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB])
Increase in anti-inflammatory cytokines and mediators
Increased conversion of T-helper cells to T-regulator cells

B cells

Decreased activity, slowing the inflammatory process

B cells

Decreased activity, slowing the inflammatory process

Cytokines

Reduction in proinflammatory cytokines and mediators (eg, TNF-α and interleukin-6)
Increase in anti-inflammatory cytokines and mediators (eg, interleukin-10)
Decrease in adhesion molecules

Cytokines

Reduction in proinflammatory cytokines and mediators (eg, TNF-α and interleukin-6)
Increase in anti-inflammatory cytokines and mediators (eg, interleukin-10)
Decrease in adhesion molecules

Macrophages

Reduction in proinflammatory cytokines and mediators
Inhibition of TNF-α release and leukocyte accumulation

Macrophages

Reduction in proinflammatory cytokines and mediators
Inhibition of TNF-α release and leukocyte accumulation

Dendritic cells

Induction of tolerogenic dendritic cells, leading to an increase in T‑regulatory cells
Decrease in costimulatory molecules to decrease T cell stimulation

Dendritic cells

Induction of tolerogenic dendritic cells, leading to an increase in T‑regulatory cells
Decrease in costimulatory molecules to decrease T cell stimulation

Osteoclasts

Decreases osteoclast numbers

Osteoclasts

Decreases osteoclast numbers

Monocytes

Decreases the production of inflammatory cytokines
Upregulates the anti-inflammatory cytokine, IL-10

Monocytes

Decreases the production of inflammatory cytokines
Upregulates the anti-inflammatory cytokine, IL-10

Fibroblasts

Decreases activity

Fibroblasts

Decreases activity

Epithelial cells

Inhibits NF-KB activation

Epithelial cells

Inhibits NF-KB activation

Watch Principal Research Pharmacologist Dale Wright, PhD, explain the potential MOA of Acthar Gel

While the exact mechanism of action of Acthar Gel is not fully understood, further investigation is being conducted. This information is based on nonclinical and pharmacodynamic data, and the relationship to clinical benefit is unknown.

NEXT: Cortisol Release and Cell Modulation

References

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IMPORTANT SAFETY INFORMATION

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 origin

INDICATIONS

Acthar^® Gel (repository corticotropin injection) is indicated 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 dermatomyositis (polymyositis)
Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); ankylosing spondylitis
Treatment of symptomatic sarcoidosis

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-adrenal (HPA) axis 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 to 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 masks 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 for additional Important Safety Information.

Acthar Gel engages melanocortin receptors (MCRs) expressed on immune cells and other tissues throughout the body1-5

Melanocortin peptides bind to and may activate melanocortin receptors on various immune cells and structural cells, including T cells, B cells, and other antigen-presenting cells1,3,6-21

T cells

T cells

B cells

B cells

Cytokines

Cytokines

Macrophages

Macrophages

Dendritic cells

Dendritic cells

Osteoclasts

Osteoclasts

Monocytes

Monocytes

Fibroblasts

Fibroblasts

Epithelial cells

Epithelial cells

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IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

Warnings and Precautions

Adverse Reactions

Acthar Gel engages melanocortin receptors (MCRs) expressed on immune cells and other tissues throughout the body^1-5

Melanocortin peptides bind to and may activate melanocortin receptors on various immune cells and structural cells, including T cells, B cells, and other antigen-presenting cells^1,3,6-21