Acthar gel (repository corticotropin injection) for multiple sclerosis

Last updated Jan. 31, 2025, by Margarida Maia, PhD
Fact-checked by Ines Martins, PhD

 

What is Acthar Gel for MS?

Acthar Gel (repository corticotropin injection) is an injectable medication used to treat acute relapses in adults with multiple sclerosis (MS).

It is marketed by Mallinckrodt Pharmaceuticals, and can be administered as injections under the skin, or subcutaneously, or into a muscle, that is intramuscularly.

While Acthar Gel can speed recovery from acute MS relapses — when new symptoms appear or existing ones worsen — there’s no evidence that it can change the long-term course of the disease.

Available in the U.S. for treating MS for more than 50 years, Acthar Gel is approved for a number of other indications, including rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and a range of other inflammatory or autoimmune diseases.

Therapy Snapshot

Brand name:	Acthar Gel
Chemical name:	Repository corticotropin injection
Usage:	Treatment of acute MS relapses
Administration:	Subcutaneous or intramuscular injection

 

How does Acthar Gel work in MS?

In MS, an uncontrolled inflammatory response causes damage to the myelin sheath, a fatty coating around nerve fibers that’s critical for normal nerve signaling. Most patients experience frequent relapses, or acute exacerbations of disease symptoms, which occur when new or worsening inflammation in the nervous system causes new problems with nerve signaling.

Acthar Gel can be used in MS patients to bring that inflammation under control, which can help reduce the severity of symptoms during relapses and speed relapse recovery.

Acthar Gel contains a mixture of molecules similar to the adrenocorticotropic hormone (ACTH) and other proteins naturally made by the brain’s pituitary gland. While its exact mechanism of action remains incompletely understood, it’s believed that Acthar Gel mainly exerts its effects by increasing cortisol levels in the bloodstream.

Cortisol is a hormone produced by the body in response to stress. Among its numerous effects, it can reduce the activity of the immune system and limit inflammation.

Acthar Gel is usually considered an alternative to corticosteroids, a common treatment for MS relapses, especially in patients who cannot tolerate or don’t respond well to those medications.

Who with MS can take Acthar Gel?

Acthar Gel was approved in the U.S. in 1972 for treating adults with MS. The U.S. Food and Drug Administration reapproved the medication in 2010.

The treatment is usually considered for MS patients who’ve had inadequate responses, or cannot tolerate, corticosteroids — medications that mimic the immune-suppressing action of cortisol and are used to help control MS relapses.

Acthar Gel also is indicated for treating 18 other conditions, including infantile spasms in infants and children younger than 2, and rheumatic, collagen, dermatologic, ophthalmic, and respiratory diseases.

Who should not take Acthar Gel?

Acthar Gel should not be used to treat people with:

• scleroderma (a disease that causes the skin to thicken and harden)
• osteoporosis (loss of bone density)
• whole-body fungal infections
• ocular herpes simplex (a type of eye infection)
• recent surgery
• a history of stomach ulcers
• heart failure
• uncontrolled high blood pressure
• abnormal function of the adrenal glands
• sensitivity to proteins of pig origin.

The therapy also should not be used in infants younger than 2 who have a suspected congenital infection, a type of infection that can be passed by the mother during pregnancy or delivery, or administered at the same time as live or live attenuated vaccines.

How is Acthar Gel administered in MS?

Acthar Gel comes in a gel formulation that allows for an extended release after injection. It’s available in 5 mL multi-dose vials containing 80 units per mL of a clear light amber solution, or in pre-filled SelfJect injectors containing a single dose of either 40 or 80 units.

Acthar Gel can be administered by patients themselves or by a trained caregiver via:

• subcutaneous injection in the upper thigh, abdomen, or upper arm
• intramuscular injection in the upper-outer thigh muscle or upper arm muscle.

The recommended dose for treating acute MS relapses is 80-120 units, given daily for two to three weeks. After this, it may be necessary to gradually decrease the dose or increase the interval between injections to avoid side effects associated with suddenly stopping the treatment.

For patients whose dose is 40 or 80 units, Acthar Gel can be administered subcutaneously using a single-dose pre-filled SelfJect injector. This all-in-one device should be easy to use from the first injection and can be useful for patients who have difficulty holding a syringe securely.

These doses can also be administered subcutaneously or intramuscularly with a regular syringe and needle containing the appropriate volume from the multi-dose vial. For doses other than 40 or 80 units, only the multi-dose vial should be used.

Acthar Gel is not intended for intravenous injection. Patients should not inject Acthar Gel in the same site more than once each week, keeping at least one inch between sites. They should avoid areas with skin irritation, tattoos, warts, or scars. Before injecting, patients should clean the site with an alcohol swab.

Acthar Gel in clinical trials

The approval of Acthar Gel was based on data from early studies that showed the medication helped patients recover from relapses faster than a placebo. More recent studies have since confirmed that Acthar Gel can speed recovery from acute exacerbations.

Prospective trials

An observational registry (NCT02633033), completed in 2019, examined the effects of Acthar Gel in patients experiencing a relapse. The registry included 145 people with a relapsing form of MS and assessed for changes in daily living after they initiated treatment with Acthar Gel.

Results showed that patients had a significant reduction in their symptoms following two months of treatment and that these improvements were sustained for up to six months. Similar improvements were seen in disability levels at these two assessments.

From doctors’ perspectives, there were also improvements in disability, fatigue, cognitive impairment, depression, and quality of life.

Optic neuritis trial

An open-label Phase 1 clinical trial (NCT01987167), called ACTHAR, tested how well Acthar Gel worked in 24 patients with acute demyelinating optic neuritis, an inflammation of the nerves that connect the eyes to the brain. Optic neuritis is common in MS and is one of the indications for which Acthar Gel is approved in the U.S.

Within two weeks of the onset of symptoms, all patients were treated with 80 units of Acthar Gel every day for five days, and then with 40 units daily for 10 days more. After a year, most patients experienced improvements in visual acuity, a measure of how well the eyes can distinguish shapes and details of objects at a given distance.

OPTIONS trial

A company-sponsored Phase 4 clinical trial, called OPTIONS (NCT03126760), tested how well Acthar Gel managed relapses in 35 adults with relapsing-remitting MS who had previously failed to respond to corticosteroids. The patients were randomly assigned to receive either 80 units of Acthar Gel, or a placebo, both given daily for 14 days.

Significantly more participants given Acthar Gel saw a reduction in disability scores in the weeks following treatment compared with the placebo group. Quality of life scores were similar between both groups.

Common side effects of Acthar Gel

The most common side effects reported with Acthar Gel include:

• injection site reactions
• fatigue, malaise, lack of energy, and lethargy
• fluid retention, including swelling in the arms and legs
• insomnia
• headache
• an increase in blood sugar.

Risk of infections

Because Acthar Gel reduces the activity of the immune system, it may increase the risk of infections. Additionally, symptoms of an infection may be less obvious during treatment.

Adrenal insufficiency and Cushing’s syndrome

After stopping long-term treatment with Acthar Gel, patients may experience hypothalamic-pituitary-adrenal axis suppression, which results in reduced cortisol production. As cortisol is necessary to respond to stressors such as infections, this may lead to an inadequate defense against infections. Dosing of Acthar Gel should therefore be decreased gradually as the treatment is discontinued to allow the body to adjust to the removal of the medication and continue to have adequate cortisol responses.

Long-term treatment with Acthar Gel may also cause the adrenal glands to produce too much cortisol. This can result in Cushing’s syndrome, a condition marked by an excess of cortisol in the body. Cushing’s symptoms usually resolve after the therapy is stopped.

Increased blood pressure

Acthar Gel may increase blood pressure and alter levels of salt and water in the body. As such, patients may be recommended to a low-salt diet and/or be advised to take potassium supplements. Blood pressure and salt levels should be monitored during treatment.

Worsening or masking of other diseases

Symptoms of underlying diseases, such as diabetes and myasthenia gravis, may worsen with the use of Acthar Gel. In turn, the effects of Acthar Gel may be more potent in people with low thyroid function or liver cirrhosis, which is a permanent scarring of the liver. Patients should be monitored for signs of other underlying diseases that may be masked.

Gastrointestinal perforation

Acthar Gel may increase the risk of stomach ulcers and gastrointestinal perforation — a tear in the gut — in people with certain gastrointestinal problems. Signs of gastrointestinal perforation may be masked by the therapy and caution is recommended when any of these issues is suspected.

Behavioral and mood changes

Treatment with Acthar Gel may cause some behavioral issues or worsen those already present. These may include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. These effects are usually reversed once the therapy is stopped.

Eye problems

Long-term treatment with Acthar Gel may increase the risk of viral and fungal infections in the eyes, as well as other eye problems like cataracts and glaucoma.

Immunogenicity risk

Acthar Gel is immunogenic, meaning patients may develop antibodies against the treatment after prolonged use. According to post-marketing reports, long-term treatment with Acthar Gel may increase the risk of serious allergic reactions.

Decreased bone density

Increased levels of cortisol may decrease calcium absorption and bone density, which may result in osteoporosis. This condition causes bones to weaken and break more easily.

Vaccination

Acthar Gel may alter a patient’s ability to respond to vaccinations due to its action on the immune system. Vaccines that contain a live virus should not be given to patients on Acthar Gel. Killed or inactivated vaccines may be administered.

Use in pregnancy and breastfeeding

Treatment with Acthar Gel may impair the development of a fetus when administered during pregnancy. Issues may include reduced weight at birth, preterm birth, and an impaired production of cortisol and other adrenal hormones.

There are no available data on the presence of Acthar Gel in human milk, and it’s also not known whether it has any impact on milk production or on a nursing infant. The decision about whether to use the treatment while breastfeeding should be made based on the relative risks and benefits for the patient, after a consultation with healthcare providers.

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