Plegridy (peginterferon beta-1a) for multiple sclerosis

 

What is Plegridy for MS?

Plegridy (peginterferon beta-1a) is an approved injectable therapy for relapsing forms of multiple sclerosis (MS) that can lower the frequency of relapses, slow disability progression, and reduce brain lesions as assessed by MRI scans. The therapy is marketed by Biogen.

Therapy Snapshot

Brand name:	Plegridy
Chemical name:	Peginterferon beta-1a
Usage:	Disease-modifying therapy for relapsing forms of MS
Administration:	Subcutaneous or intramuscular injection

 

How does Plegridy work?

In MS, the immune system accidentally attacks and damages components of the myelin sheath, a fatty substance that covers nerve cells and is needed for efficient nerve communication.

Plegridy contains a modified version of interferon beta-1a, a naturally occurring signaling molecule that immune cells use to reduce excessive inflammatory responses.

It works similarly to other interferon beta-1a medications, such as Rebif or Avonex, but the interferon molecules in Plegridy are “pegylated” — which means they are modified with a chemical polymer called polyethylene glycol, or PEG. This enables the therapy to maintain its biologic effects for longer periods of time, allowing for less frequent dosing.

The mechanisms through which Plegridy and other interferon therapies work in MS are not exactly clear, but broadly, these medicines are thought to alter immune activity in a manner that reduces the autoimmune attack on the nervous system.

Who can take Plegridy?

The U.S. Food and Drug Administration (FDA) approved Plegridy in 2014 for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive MS.

In the European Union, Plegridy also was approved in 2014, but only for people with RRMS.

According to Biogen, the treatment is available in more than 60 countries worldwide, including Canada, Australia, and Switzerland.

Who should not take Plegridy?

The therapy is not recommended for people with known allergies to interferon beta, peginterferon, or any other component in Plegridy.

How is Plegridy administered?

Plegridy is an injectable medication that has two possible routes of administration:

• a subcutaneous, or under-the-skin, injection
• an intramuscular injection, given into the muscle

The recommended dose is 125 micrograms (mcg), administered via an injection every 14 days.

Notably, the first doses can cause flu-like symptoms in patients. Thus, people starting on the medication will gradually increase their dose over the first month, receiving 63 mcg on day 1, 94 mcg on day 15, and reaching the full 125 mcg dose on day 29.

This titration step can look different depending on the administration method. For patients prescribed the subcutaneous formulation, it involves receiving a Plegridy starter pack, which includes:

• an orange pen or pre-filled syringe containing 63 mcg for day 1
• a blue pen or pre-filled syringe containing 94 mcg for day 15

Subsequent injections are given with a gray pen or prefilled syringe containing the recommended 125 mg dose. These under-the-skin injections should be preferably given in the stomach region (abdomen), the back of the upper arm, or the thigh.

Intramuscular injections are all done with a 125 mcg pre-filled syringe, and preferably given in thigh muscle. But patients prescribed this formulation will receive a Plegridy titration kit containing two colored devices that ensure that the correct dose is injected during the initiation period. These devices include:

• a yellow clip, which enables the injection of half a dose (63 mcg)
• a purple clip that allows the delivery of three-quarters of a dose (94 mcg)

The pre-filled syringes and pens for both administration routes are not shareable and should not be reused. The treatment can be self-administered at home by patients who have been trained in how to perform injections. However, the first injection should be given in a hospital by a qualified healthcare provider.

Importantly, patients should rotate the place of injection to avoid injection site reactions, including infection or tissue death (necrosis). It may be helpful to keep a log listing administration sites. Overall, intramuscular injections have a lower risk of injection site reactions as compared with subcutaneous treatment.

Skin areas that are irritated, reddened, bruised, infected, or scarred should be avoided. People who are allergic to latex also should not handle the pre-filled syringes used for intramuscular injections, as they have a protective rubber latex cover.

Taking painkillers or anti-fever medications before the injections may help improve flu-like symptoms caused by the treatment.

The medication should be refrigerated but not frozen. If a refrigerator is not available, Plegridy may be stored at room temperature and away from light for up to 30 days.

Administration	Subcutaneous injection in stomach region (abdomen), the back of the upper arm, or the thigh or intramuscular injection in the thigh muscle
Dosage	Recommended dose of 125 mcg; titration kit includes 63 mcg dose for day 1 and 94 mcg for day 15
Timing	Every 14 days

 

Plegridy in clinical trials

Plegridy’s approval was supported by data from a Biogen-sponsored Phase 3 trial, called ADVANCE (NCT00906399), which involved 1,512 adults with RRMS. The participants were randomly assigned to receive a placebo or 125 mcg of the active medication, given every two or every four weeks, for 48 weeks, or about one year.

Results showed that Plegridy given every other week significantly reduced relapse rates, by 36%, compared with a placebo. Additionally, it lowered the risk of three-month confirmed disability progression by 38% relative to the placebo. The number of new or enlarging brain lesions on MRI scans also was significantly lowered with this Plegridy regimen, with a relative reduction of 67%. Those on Plegridy also had significantly fewer and smaller lesions with active inflammation.

After the first year, participants who were in the placebo group were randomly assigned to receive one of the two Plegridy regimens. Meanwhile, those originally assigned the active medication continued on the same dosing regimen for another 48 weeks. In this second part, relapse rates and brain lesions continued to drop among patients on continuous Plegridy from the start of ADVANCE; those on the every-two-week regimen continued to show better outcomes than those receiving less frequent dosing.

ATTAIN trial

Participants who completed the two-year ADVANCE trial were given the option to join an open-label extension study called ATTAIN (NCT01332019), in which all received their assigned Plegridy regimen for at least 96 weeks, nearly two years. A total of 842 patients completed this extension part, and some received nearly six years of treatment in total.

Trial results confirmed the long-term safety and tolerability profile of Plegridy in RRMS patients. In fact, over the years, relapse rates for individuals treated every two weeks continued to lower. Specifically, there were 0.241 relapses per year in the first year on ADVANCE, which dropped to 0.055 relapses per year in year five. Over five years, these patients also had a lower risk of experiencing disability progression, and their number of MRI lesions continued to be lower than for those on every-four-week Plegridy.

Ongoing trials

This medication is currently approved only for adults. An ongoing Phase 3 trial (NCT03958877) is assessing the safety and efficacy of Biogen’s interferon-based therapies, Plegridy and Avonex, in children and adolescents with RRMS.

About 142 patients, ages 10 to 17, will receive treatment for 96 weeks, after which they will have the option to enter a long-term extension phase and continue to receive Plegridy for two more years.

The main goals are to determine the safety of these therapies in pediatric patients, and to assess their effects on relapse rates after 96 weeks. Secondary measures include changes in brain lesions and cognition, as well as disability worsening and quality of life. The study is expected to be completed in 2029.

Common side effects of Plegridy

In clinical trials, the most common side effects associated with the subcutaneous formulation of Plegridy were:

• injection site reactions, such as redness, pain, and itching
• flu-like symptoms
• fever
• headache
• muscle pain
• chills
• lack of energy
• joint pain

Injection site reactions

Injection site reactions occur in the majority of people receiving Plegridy or other interferon-based medications. These normally include redness, pain, itching, or tissue swelling, but some patients can experience necrosis (tissue death). In such cases, the medication should not be injected close to an affected area until it fully heals, and treatment cessation may be considered.

Low blood counts

The therapy can cause a decrease in the number of white blood cells and platelets, which may increase the risk of infections and lead to problems such as excess bleeding and bruising. Patients on Plegridy should be regularly monitored for blood cell counts, infections, bleeding, and symptoms of anemia.

Liver injury

There have been some rare cases of severe liver problems in people receiving interferon-based therapies like Plegridy. Liver health should be monitored while on the medication, and treatment cessation may be considered if signs of liver damage become evident.

Heart problems

While no serious cardiovascular side effects have been reported for Plegridy, heart failure and other conditions affecting the heart muscle have occurred in patients receiving other interferon-based medications. Patients with heart disease should be routinely monitored for worsening cardiac symptoms.

Blood vessel damage

Interferon-based products also have been associated with cases of thrombotic microangiopathy, a condition in which blood clots contribute to small vessel damage. Plegridy should be discontinued if signs of this disease occur, and patients should be managed accordingly.

Autoimmune diseases

Cases of autoimmune diseases affecting multiple organs, most commonly the thyroid and liver, have occurred after treatment with interferon medications. Treatment may be discontinued in anyone who develops a new autoimmune disease.

Psychological issues

Plegridy carries a warning for depression and suicidal ideation, or thoughts about self-harm. Patients who develop depression or severe psychological symptoms should immediately report these signs to their healthcare team, and consider stopping the medication.

Seizures

Seizures have been reported in rare instances in patients taking Plegridy. Treatment should be given with caution to patients with seizure disorders.

Allergic reactions

Serious allergic reactions to Plegridy can occur. The medication should not be given to anyone with a known allergy to any of its components, and should be stopped if a serious allergic reaction occurs.

Pregnancy and breastfeeding

Large registry and observational studies suggest that Plegridy and other interferon-based therapies do not increase the risk of major birth defects or adverse pregnancy outcomes. Plegridy may be used with caution in patients who are pregnant or breastfeeding, but patients should discuss with their healthcare team the benefits and risks of continuing treatment during these periods.

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