Acthar gel (repository corticotropin injection) for multiple sclerosis
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What is Acthar Gel for MS?
Acthar Gel (repository corticotropin injection) is an injectable therapy that is used to manage acute relapses in people with multiple sclerosis (MS).
Although Acthar Gel can help to speed recovery from relapses — when new symptoms appear or existing ones suddenly worsen — it does not alter the natural progression of MS.
Available in the U.S. for MS for more than 40 years, the therapy is marketed by Mallinckrodt Pharmaceuticals.
Therapy Snapshot
| Brand name: | Acthar Gel |
| Chemical name: | Repository corticotropin injection |
| Usage: | Relapse management therapy for acute MS exacerbations |
| Administration: | Subcutaneous or intramuscular injection |
How does Acthar Gel work?
Cortisol is a hormone that the body produces in response to stress. This hormone has numerous effects throughout the body, working to manage metabolism and control mood, among other things.
A particularly relevant effect of cortisol for MS and other inflammatory conditions is a reduction in the activity of the immune system.
The active agent in Acthar Gel, called corticotropin or adrenocorticotropic hormone (ACTH), is a naturally occurring hormone that stimulates the production of cortisol in the body. The exact mechanism of action of Acthar Gel remains incompletely understood. But it is thought to mainly exert its effects in MS by increasing cortisol levels and, consequently, decreasing the activity of the immune system and reducing inflammation.
Acthar Gel also seems to bind to melanocortin receptors on the surface of certain immune cells and exert direct immunosuppressive effects, including in cells known to contribute to the inflammatory immune responses in MS.
Who with MS can take Acthar Gel?
Acthar Gel has been approved in the U.S. for adults with MS since the 1970s. In 2010, the U.S. Food and Drug Administration reapproved the medication.
The treatment is usually considered for MS patients who have had inadequate responses, or cannot tolerate, corticosteroids — medications that mimic the immune-suppressing action of cortisol and are also used to help control MS relapses.
Acthar Gel also is indicated for the treatment of 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 characterized by thick and hardened skin)
- osteoporosis (weak bones)
- fungal infections
- ocular herpes simplex (a type of eye infection)
- recent surgery
- history of stomach ulcers
- heart failure
- uncontrolled high blood pressure
- abnormal function of the adrenal glands.
The therapy also should not be used in infants younger than 2 who have suspected congenital infections, or for those with sensitivity to proteins of porcine (pig) origin.
Acthar Gel should also not be given at the same time as live or live attenuated vaccines (concomitant administration is contraindicated).
How is Acthar Gel administered in MS?
Available in 5 mL multi-dose vials containing 80 units per mL, the treatment is a gel formulation that allows an extended release after injection. It may be administered via:
- subcutaneous (under-the-skin) injection
- intramuscular (into-the-muscle) injection
The medication should never be injected intravenously, or directly into the bloodstream.
The recommended dosage for MS relapse treatment is 80–120 units (1–1.5 mL), given daily for two to three weeks. After this period, it may be necessary to gradually decrease the dose to avoid side effects associated with suddenly stopping the treatment.
Acthar Gel may be self-administered or given by a caregiver, but both routes require previous training by a healthcare provider.
The medication should be refrigerated at 36 to 46 degrees Fahrenheit 46 F (2 to 8 degrees Celsius). Patients should take the Acthar Gel vial out of the refrigerator 15 to 30 minutes before injecting the medication. That will allow the medicine to get to room temperature prior to its use. To warm it more quickly, patients can roll the vial between the palms of their hands or hold it under their arm for a few minutes.
Different sized needles might be needed: typically, a 20G needle for drawing up Acthar Gel into the syringe, and then a 23G needle for injecting the medication into the body.
Subcutaneous injection may be administered in the upper thigh, abdomen, and side or back of the upper arm. Intramuscular injection can be given in the upper-outer thigh muscle and the upper arm muscle.
Patients should not inject the medication in the same area more than once a week and should keep 1 inch of distance between injection sites. Areas that have skin irritation, tattoos, warts, or scars should be avoided. The injection site should be cleaned with an alcohol swab before administering Acthar Gel.
| Administration | Subcutaneous injection in the upper thigh, abdomen, and side or back of the upper arm or intramuscular injection in the upper-outer thigh muscle and the upper arm muscle |
| Dosage | Recommended dose of 80–120 units (1 to 1.5 mL) |
| Timing | Daily for two to three weeks |
Acthar Gel in clinical trials
The approval of Acthar Gel was based on data from earlier studies demonstrating that the medication helped patients recover from relapses faster than a placebo. More recent studies have since proven Acthar Gel’s ability to accelerate relapse recovery.
Prospective trials
Mallinckrodt sponsored an open-label clinical trial (NCT02633033), completed in 2019, in which Acthar Gel was administered to patients experiencing a relapse. The study’s primary goal was to assess the effect of the medication on symptoms associated with MS relapses after two months of treatment, based on the MSIS-29 impact scale. MSIS-29 measures the impact of MS in physical and psychological aspects from a patient’s perspective.
Results showed that patients had a significant reduction in their symptoms following two months of therapy and that these improvements were sustained at six months. Similar improvements also were seen in assessments of disability severity, and in clinician-reported measures of patient welfare.
Optic neuritis trial
An open-label study (NCT01987167) tested the therapy’s effects in 24 patients with relapsing-remitting MS (RRMS) and related acute demyelinating optic neuritis — an inflammatory condition affecting the main nerve of the eye. All patients were treated with Acthar Gel within two weeks of symptom onset with 80 units for five days followed by 40 units for 10 days.
An improvement in visual acuity — the eye’s ability to distinguish shapes and details of objects at a given distance — was shown in some patients, according to the results.
Optic neuritis is one of the ophthalmic diseases for which Acthar Gel is approved in the U.S.
OPTIONS trial
A Phase 4 trial called OPTIONS (NCT03126760) investigated whether Acthar Gel could be useful for managing relapses in patients who previously had failed to respond to corticosteroids. In the trial, 35 participants with RRMS were randomly assigned to receive either Acthar Gel or a placebo. Results showed that significantly more participants given Acthar Gel experienced a reduction in disability scores in the weeks following treatment compared with the placebo group. Quality of life scores were similar between both groups.
Ongoing trials
A randomized Phase 2 clinical trial (NCT01950234) is assessing the safety and efficacy of repeated treatments with Acthar Gel in patients with progressive forms of MS. The trial will evaluate whether Acthar Gel can slow the progression of the disease based on clinical measures, namely in terms of mobility and cognitive disability.
Participants are receiving either Acthar Gel or a placebo as a pulsed regimen of injections for three consecutive days per month. The trial is expected to be completed in June 2022.
Common side effects of Acthar Gel
The most commonly reported side effects associated with Acthar Gel include:
- injection site reactions
- fatigue, malaise, and lethargy
- fluid retention or swelling
- headache
- insomnia
- elevated blood sugar
Other less common side effects should also be taken into consideration. Namely:
Risk of infections
Since it lowers immune activity, Acthar Gel 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 can cause an inadequate defense against infection. This side effect may be minimized by gradually decreasing the dose as the treatment is discontinued.
Long-term use of Acthar also may cause the adrenal gland to produce too much cortisol. This can result in Cushing’s syndrome, a condition characterized by an excess of cortisol hormone 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 a low-salt diet and/or advised to take supplements. Blood pressure and salt levels should be monitored during treatment.
Worsening of or masking other diseases
Symptoms of underlying diseases, such as diabetes and myasthenia gravis, may worsen with the use of Acthar Gel. Also, the medicine’s effects may be enhanced in people with low thyroid function or liver cirrhosis. Patients should be monitored for signs of other underlying conditions that may be masked.
Gastrointestinal perforation
Acthar Gel may increase the risk of gastric ulcers and gastrointestinal perforation — a tear in the gut — in people with certain gastrointestinal conditions. Signs of such perforation may be masked by the therapy.
Behavioral and mood changes
Treatment with Acthar Gel may cause some behavioral issues and aggravate pre-existing ones. Such issues include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis.
Eye problems
Long-term treatment with Acthar Gel may increase the risk of viral and fungal infections, as well as other eye problems like cataracts and glaucoma. Patients with ocular herpes simplex should avoid this treatment.
Immunogenicity Risk
Acthar Gel is immunogenic, meaning that 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.
Effects on growth and physical development
Prolonged use of Acthar Gel may slow growth and physical development in children. This may be in part due to changes in appetite observed during the treatment. These effects are more frequent with higher doses or longer treatment periods, but generally resolve after the therapy is stopped. Children taking Acthar Gel for long periods should be carefully monitored for growth and physical development.
Decreased bone density
Increased levels of cortisol may decrease calcium absorption and bone density, which can potentially lead to osteoporosis. In this condition, bones become weak and break more easily.
Vaccination
Acthar Gel may alter a patient’s ability to respond to vaccinations due to its action on immune activity. Vaccines that contain a living 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 during pregnancy. The decision of whether to use the medicine during pregnancy or lactation should be made based on the relative risks and benefits for the patient, after consultation with healthcare providers.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Acthar Gel
Acthar Gel was approved by the U.S. Food and Drug Administration in the 1970s for the treatment of multiple sclerosis. It was re-approved in 2010. The medicine had originally been approved in the U.S. in 1952 for several conditions, such as collagen diseases, inflammatory diseases of the skin and the eye, metabolic disorders, and allergic states, among others.
Acthar Gel may cause harm to a developing fetus. Patients should talk with their healthcare team and only continue Acthar Gel during pregnancy if the potential benefits justify the possible risks to the fetus.
The prescribing information for Acthar Gel does not report a direct interaction between the medication and alcohol. However, given that alcohol can interfere with some medications and disease symptoms, patients are advised to discuss this topic with their healthcare provider.
According to Mallinckrodt Pharmaceuticals, which markets Acthar Gel, patients with multiple sclerosis (MS) taking the therapy reported clinically significant improvements in physical and psychological status after two months of treatment. These improvements were maintained six months after starting the medication. An improvement in MS-related eye problems, namely visual impairment due to optic neuritis, also was reported in patients after 15 days of treatment with Acthar Gel. Nonetheless, it is important to keep in mind that each patient may respond to treatment in a different way.
Changes in body weight may occur. Patients who develop Cushing’s syndrome while on Acthar Gel may have greater deposits of fat resulting in weight gain; however, this usually resolves after therapy is stopped. Hair loss has not been reported as a side effect in people taking Acthar Gel. Patients should be monitored for these signs and should report any such symptoms to their healthcare providers.
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