What is Acthar Gel?
Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides.1
How is Acthar Gel believed to work?
Acthar Gel engages melanocortin receptors (MCRs) expressed on immune, organ, and tissue cells throughout the body and is thought to produce both an indirect anti-inflammatory effect and a direct cell modulation effect.2-6
*While the exact mechanism of action of Acthar Gel is unknown, further investigation is being conducted. This information is based on nonclinical data and the relationship to clinical benefit is unknown.
*While the exact mechanism of action of Acthar Gel is unknown, further investigation is being conducted. This information is based on nonclinical data and the relationship to clinical benefit is unknown.
Acthar Gel engages receptors on the adrenal cortex to secrete free cortisol at levels slightly above normal endogenous range, producing a potential indirect anti-inflammatory effect7,8

Acthar Gel AUC24=324 ± 61 h*ng/mL
†The prednisone-equivalent range of normal endogenous cortisol is 5 mg–7.5 mg.8
This information is based on pharmacodynamic data and the relationship to clinical benefit is unknown.
After 5 doses of 80 U twice per week, Acthar Gel's prednisone-equivalent daily cortisol exposure above normal endogenous range is between 1.3 mg and 3.8 mg of prednisone.7,8
Pharmacodynamic studies: These data are from an independent study in healthy adult subjects.7 Data presented are following a single dose given on the first day.
Study design: An open-label, single-center, randomized, multiple-dose, parallel-group study to compare the pharmacodynamics (PD) and safety of intermittent doses of Acthar Gel to daily oral methylprednisolone (MP) in healthy subjects. Subjects between 18 and 50 years old were randomized to receive Acthar Gel 40 U or 80 U subcutaneously twice weekly for 15 days (n=12/group) or 16 mg of oral MP given once daily for 15 days (n=12), followed by a tapering regimen of 8 mg daily for 2 days, then 4 mg daily for 2 days. The most frequently reported treatment emergent adverse events (TEAEs) that occurred in 2 or more subjects were (in decreasing order of frequency): injection site hemorrhage, headache, injection site erythema, injection site pruritus, insomnia, acne, infrequent bowel movements, and injection site pain. All TEAEs experienced during this study were considered mild in severity.7
Study limitations: As this was a healthy-subject, open-label study with no placebo control, the clinical relevance of differences in tolerability is unknown and remains to be investigated for patient populations.7
Acthar Gel has shown a direct modulatory effect on B cells, independent of cortisol release
In an in vitro study using human B cells, Acthar Gel reduced B-cell proliferation and IgG production independent of cortisol release.3,10


‡P<0.05 versus vehicle-treated group.
This information is based on nonclinical data and the relationship to clinical benefit is unknown.
Study design: The effects of Acthar Gel on human B-lymphocyte function in vitro were evaluated using highly purified B-cell populations cultured in the absence of glucocorticoids and stimulated by recombinant IL-4 and CD40 ligand (CD40L) as specific B-cell activating signals. IgG was measured in supernatants from healthy human peripheral B cells cultured for 6 days. Percentage of cells that divided and IgG production were assessed under basal conditions (unstimulated), or stimulated with IL-4/CD40L alone (vehicle), or with IL-4/CD40L plus a 1:22 dilution of 80 U/mL stock of Acthar Gel.3,10
Acthar Gel has shown a direct immunomodulatory effect on monocyte-derived macrophages (MDMs), independent of cortisol release
In an in vitro study using human MDMs, Acthar Gel inhibited proinflammatory cytokines IL-6 and TNF-α, indicating an anti-inflammatory effect independent of cortisol release.5


§P<0.0001 versus vehicle-treated group.
This information is based on nonclinical data and the relationship to clinical benefit is unknown.
Study design: An in vitro study to explore the direct effects of Acthar Gel on human macrophages, focusing on induction of proinflammatory mediators following lipopolysaccharide (LPS) stimulation. Human blood derived monocytes were selected for CD14 expression using magnetic bead selection (MACS) and plated in presence of macrophage colony-stimulating factor (M-CSF). Cells were stimulated with LPS and incubated for a minimum of 24 hours with and without a 1:11 dilution of 80 U/mL stock of Acthar Gel. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA).5