Plegridy
Peginterferon Beta-1a for Relapsing Multiple Sclerosis
Quick Facts About Plegridy
Key Takeaways About Plegridy
- Less frequent dosing: Plegridy is injected only once every 14 days, compared to the daily or three-times-weekly injections required by non-PEGylated interferons
- Proven relapse reduction: Clinical trials (ADVANCE) demonstrated a 36% reduction in annualised relapse rate compared to placebo over one year
- Flu-like symptoms are common initially: Most patients experience flu-like side effects at the start of treatment, but these typically diminish over the first few months
- Gradual dose titration: Treatment begins with a starter pack (63 mcg, then 94 mcg) before reaching the full 125 mcg maintenance dose to minimise side effects
- Regular monitoring required: Blood tests for liver function, blood cell counts, and thyroid function should be performed before and during treatment
What Is Plegridy and What Is It Used For?
Plegridy contains peginterferon beta-1a, a PEGylated (long-acting) form of interferon beta-1a. It is used to treat relapsing-remitting multiple sclerosis (RRMS) in adults aged 18 years and older. Plegridy helps reduce the number of relapses and slows the progression of physical disability caused by MS.
Interferons are naturally occurring proteins produced by the body to help protect against infections and regulate the immune system. In multiple sclerosis, the immune system mistakenly attacks the protective myelin sheath that surrounds nerve fibres in the brain and spinal cord (the central nervous system). This damage disrupts the transmission of nerve signals between the brain and the rest of the body, causing the characteristic symptoms of MS.
Plegridy works by modulating the immune response. Specifically, it is believed to reduce the activity of immune cells that attack myelin, decrease the production of pro-inflammatory cytokines, and promote anti-inflammatory pathways. The result is a reduction in the inflammatory damage to the central nervous system, which translates into fewer relapses and slower disability progression for many patients.
What distinguishes Plegridy from older interferon beta preparations is the process of PEGylation – the attachment of polyethylene glycol (PEG) molecules to the interferon protein. PEGylation increases the molecular size of the drug, which slows its breakdown and clearance from the body. This extended half-life is what allows Plegridy to be administered only once every 14 days, rather than the daily or thrice-weekly injections required by conventional interferon beta products such as Avonex, Rebif, or Betaferon.
The approval of Plegridy was based primarily on the ADVANCE trial, a large, randomised, double-blind, placebo-controlled phase III study involving over 1,500 patients with relapsing-remitting MS. This study demonstrated that Plegridy significantly reduced the annualised relapse rate by 36% compared to placebo at one year. It also showed significant reductions in new or newly enlarging brain lesions on MRI, supporting its disease-modifying effect. Long-term extension data (ATTAIN study) confirmed that the benefits of Plegridy were maintained over several years of treatment.
Plegridy was first approved by the European Medicines Agency (EMA) in 2014 and by the US Food and Drug Administration (FDA) in the same year. It is manufactured by Biogen, one of the leading companies in multiple sclerosis therapeutics. The convenient every-two-week dosing schedule is a significant advantage for patients who find frequent self-injection burdensome.
It is important to understand that Plegridy is not a cure for multiple sclerosis. It is a disease-modifying therapy (DMT) that aims to reduce disease activity. Patients with relapsing-remitting MS experience periods where the disease is quiet (remission) interspersed with episodes of new or worsening symptoms (relapses). Plegridy helps to extend the remission periods and reduce the severity and frequency of relapses. The symptoms of MS vary widely between individuals but can include balance problems, dizziness, difficulty walking, muscle stiffness and spasms, fatigue, numbness in the face, arms, or legs, pain, bladder and bowel problems, sexual dysfunction, visual disturbances, and difficulties with thinking and concentration.
What Should You Know Before Using Plegridy?
Before starting Plegridy, inform your doctor about all your medical conditions, particularly any history of depression, liver disease, kidney problems, epilepsy, or heart disease. Plegridy must not be used if you have severe depression or suicidal thoughts, or if you are allergic to interferon beta or any of its excipients.
Contraindications
You should not use Plegridy if any of the following apply to you:
- Allergy to peginterferon beta-1a, interferon beta-1a, or any excipient – allergic reactions can include difficulty breathing, facial swelling (lips, tongue, or throat), rash, or skin redness. See the side effects section for more details on symptoms of allergic reactions.
- Severe depression or suicidal thoughts – interferons can worsen pre-existing depression and, in rare cases, contribute to suicidal ideation. If you currently have severe depression or are experiencing thoughts of self-harm, Plegridy is contraindicated.
Warnings and Precautions
Talk to your doctor, pharmacist, or nurse before injecting Plegridy if you have or have had any of the following conditions. Treatment may still be possible, but closer monitoring or dose adjustments may be required:
- Depression or mood disorders – even if your depression has been treated or resolved in the past, let your doctor know. Interferon therapy has been associated with worsening of depression and, uncommonly, suicidal behaviour. Your mental health should be monitored throughout treatment.
- Serious liver or kidney disease – Plegridy can affect liver function, and liver enzymes should be monitored before and during treatment. Pre-existing liver impairment may increase the risk of hepatotoxicity.
- Epilepsy or seizure disorders – particularly if seizures are not adequately controlled with current medication. Interferons may lower the seizure threshold in some patients.
- Heart problems – including angina pectoris, congestive heart failure, or cardiac arrhythmias. Flu-like symptoms associated with Plegridy (fever, chills) can place additional stress on the cardiovascular system.
- Thyroid disorders – interferons can affect thyroid function, and thyroid tests should be performed before starting treatment and periodically thereafter.
- Low white blood cell or platelet counts – which may increase the risk of infections or bleeding. Regular blood count monitoring is essential.
You will need regular blood tests before and during treatment with Plegridy. These include complete blood counts, liver enzymes, and thyroid function tests. Your doctor will determine the frequency of these tests based on your individual risk profile.
Children and Adolescents
Plegridy is not approved for use in children and adolescents under 18 years of age, as the safety and efficacy in this population have not been established. Some clinical data from studies in children aged 10 years and older exist, but the evidence is insufficient to support a specific dosing recommendation for paediatric patients.
How Does Plegridy Interact with Other Drugs?
Plegridy should be used with caution alongside medications metabolised by the cytochrome P450 enzyme system (CYP450), particularly drugs used to treat epilepsy or depression. Interferons can alter the activity of CYP450 enzymes, potentially changing the blood levels and effects of co-administered drugs.
Drug interactions with Plegridy are relatively limited compared to many oral medications, primarily because it is a biologic agent (a large protein) rather than a small molecule processed through typical hepatic metabolic pathways. However, there are several clinically important considerations:
Interferons are known to modulate the expression of hepatic cytochrome P450 enzymes, particularly during periods of inflammation and immune activation. This means that when you start or stop Plegridy, the metabolism of certain co-administered drugs may change. Your doctor may need to adjust the doses of these medications, particularly those with a narrow therapeutic index – drugs where a small change in blood level can significantly affect efficacy or toxicity.
| Drug / Drug Class | Type | Clinical Significance |
|---|---|---|
| Antiepileptic drugs (e.g. phenytoin, carbamazepine) | CYP450 interaction | Monitor drug levels; dose adjustment may be needed when starting or stopping Plegridy |
| Antidepressants (e.g. SSRIs, tricyclics) | CYP450 interaction | Monitor for increased or decreased antidepressant effects; dose adjustment may be required |
| Warfarin | CYP450 interaction | Monitor INR closely; anticoagulant effect may be altered |
| Theophylline | CYP450 interaction | Narrow therapeutic index; monitor levels when initiating or stopping interferon therapy |
| Immunosuppressants | Pharmacodynamic | Combining immunomodulators with immunosuppressants may increase the risk of infections; use with caution |
Always inform your doctor, pharmacist, or nurse about all medications you are taking, including over-the-counter medicines and herbal supplements. You may also need to remind other healthcare professionals that you are receiving Plegridy treatment, as it may affect the interpretation of certain blood test results.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using Plegridy. Your doctor will discuss the potential benefits and risks with you on an individual basis.
Regarding breastfeeding, no harmful effects on breastfed newborns or infants are expected. Plegridy can be used during breastfeeding. The small molecular size of the PEGylated interferon that may pass into breast milk is unlikely to cause significant absorption in the infant’s gastrointestinal tract.
Driving and Using Machines
Plegridy has no or negligible effect on the ability to drive and use machines. However, some patients may experience dizziness or fatigue as part of flu-like symptoms following injection. If you are affected, you should avoid driving or operating machinery until the symptoms resolve.
What Is the Correct Dosage of Plegridy?
The standard maintenance dose of Plegridy is 125 micrograms injected subcutaneously every 14 days (every other week). Treatment is started with a gradual dose titration using a starter pack: 63 mcg on day 0, 94 mcg on day 14, then 125 mcg from day 28 onwards.
Plegridy should always be used exactly as your doctor has told you. The dose titration at the start of treatment is designed to allow your body to adjust to the medication and to minimise the flu-like symptoms that are common during the initial phase of interferon therapy. The starter pack contains two pre-filled pens: an orange pen with 63 micrograms (for day 0) and a blue pen with 94 micrograms (for day 14). Maintenance pens are grey and contain 125 micrograms each.
| Time Point | Dose | Pen Colour | Notes |
|---|---|---|---|
| Day 0 (First injection) | 63 mcg | Orange | Starter pack – first injection |
| Day 14 | 94 mcg | Blue | Starter pack – second injection |
| Day 28 and every 14 days thereafter | 125 mcg | Grey | Full maintenance dose |
How to Inject Plegridy
Plegridy is administered as a subcutaneous injection (under the skin). You can inject yourself after your doctor or nurse has shown you the correct technique. Key points for self-injection include:
- Injection sites: Suitable areas include the thigh, abdomen, or the back of the upper arm. Rotate the injection site each time – do not inject in the same spot consecutively.
- Preparation: Remove the pen from the refrigerator and allow it to warm to room temperature for at least 30 minutes. Do not use external heat sources (such as warm water) to speed up warming.
- Inspection: Check the viewing window to ensure the solution is clear and colourless. Do not use the pen if the solution is cloudy, discoloured, or contains particles.
- Injection: Clean the injection site with an alcohol swab. Remove the cap from the pen. Hold the pen at a 90-degree angle to the skin and press firmly – you will hear a click when the injection starts. Continue holding until the clicking stops and you see green check marks in the status window.
- After injection: Dispose of the used pen safely. Do not recap the pen. Check the injection site after 2 hours for any persistent redness, swelling, or tenderness.
Missed Dose
If you miss your scheduled injection day, inject as soon as you remember. Then continue with your regular schedule. However, do not inject more than once within a 7-day period. Never use two injections to compensate for a missed dose. The regular every-14-day schedule helps ensure consistent drug levels in your body.
Overdose
Plegridy should only be administered once every 14 days. If you accidentally use more than one injection within a 7-day period, contact your doctor or nurse immediately. While single overdose events are unlikely to be dangerous, using the medication too frequently may increase the severity of side effects, particularly flu-like symptoms, liver enzyme elevations, and blood count changes.
Duration of Treatment
Your doctor will advise you on how long to continue using Plegridy. It is important to use Plegridy regularly and consistently as prescribed. Do not change the dose or stop treatment without first consulting your doctor. Multiple sclerosis is a chronic condition, and disease-modifying therapies like Plegridy are typically used long-term to maintain disease control. Stopping treatment may lead to a return of disease activity.
What Are the Side Effects of Plegridy?
The most common side effects of Plegridy are flu-like symptoms (headache, muscle pain, joint pain, chills, fever, fatigue) and injection site reactions. These are most pronounced at the start of treatment and typically decrease over time. Serious but less common side effects include liver problems, depression, severe allergic reactions, and seizures.
Like all medicines, Plegridy can cause side effects, although not everyone experiences them. The frequency and severity of side effects often decrease as your body adjusts to the medication over the first few months of treatment. Understanding the possible side effects and knowing when to seek medical attention is an important part of managing your treatment safely.
Very Common
- Flu-like symptoms (not actual influenza – you cannot pass it to others)
- Headache
- Muscle pain (myalgia)
- Joint pain, arm, leg, or neck pain (arthralgia)
- Chills
- Fever
- Feeling of weakness and tiredness (asthenia)
- Redness, itching, or pain at the injection site
Common
- Nausea or vomiting
- Hair loss (alopecia)
- Itchy skin (pruritus)
- Increased body temperature
- Injection site changes (swelling, inflammation, bruising, warmth, rash, or discolouration)
- Changes in blood counts that may cause tiredness or reduced ability to fight infection
- Increased liver enzymes (shown in blood tests)
- Depression
- Liver problems (jaundice, generalised itching, nausea, easy bruising)
Uncommon
- Hives (urticaria)
- Changes in blood counts that may cause unexplained bruising or bleeding
- Severe allergic reaction (anaphylaxis) – difficulty breathing, facial swelling, rash
- Seizures
Rare
- Injection site necrosis (tissue damage) – a wound with swelling, inflammation, or fluid leakage around the injection site
- Kidney problems including scarring that may reduce kidney function (foamy urine, fatigue, swelling in ankles or eyelids, weight gain)
- Blood clots in small blood vessels (thrombotic thrombocytopenic purpura / haemolytic uraemic syndrome) – increased bruising, bleeding, fever, extreme weakness, headache, dizziness
Flu-like symptoms are most common when you first start Plegridy and tend to diminish over time. Three practical strategies can help:
- Timing: Choose an injection time that allows the flu-like symptoms (which typically start ~10 hours after injection and last 12–24 hours) to occur while you can rest, such as a Friday evening.
- Pre-medication: Take paracetamol (acetaminophen) or ibuprofen 30 minutes before the injection and continue taking it as needed for flu-like symptoms. Ask your doctor or pharmacist about appropriate dosing.
- Hydration: If you develop a fever, drink plenty of water to prevent dehydration.
Reporting of Side Effects
If you experience any side effects, particularly those not listed above or those that become severe, talk to your doctor, pharmacist, or nurse. You can also report side effects directly to your national pharmacovigilance agency. By reporting side effects, you help provide ongoing safety information about this medicine.
How Should You Store Plegridy?
Store Plegridy in a refrigerator at 2–8°C in the original packaging to protect from light. Do not freeze. If needed, Plegridy can be stored at room temperature (up to 25°C) for a total of up to 30 days, but must be protected from light.
Correct storage of Plegridy is essential to maintain the integrity and effectiveness of the medication. As a biologic product, peginterferon beta-1a is sensitive to temperature extremes, light, and physical damage. Follow these guidelines carefully:
- Refrigerator storage (recommended): Keep the pre-filled pens in the refrigerator at 2–8°C. Store in the original packaging to protect from light.
- Do not freeze: If a pen has been accidentally frozen, discard it. Freezing can damage the protein structure and render the medication ineffective.
- Room temperature storage: Plegridy can be kept at room temperature (up to 25°C) for up to 30 days total if necessary. It can be moved in and out of the refrigerator multiple times, but the cumulative time outside the refrigerator must not exceed 30 days.
- Light protection: Always keep the pens in their original packaging, whether stored in the refrigerator or at room temperature.
- Before use: Check the expiry date on the carton and label. Do not use the pen if the expiry date has passed, if the pen appears damaged, or if the solution is coloured, cloudy, or contains visible particles.
- Disposal: Do not dispose of used pens in household waste. Ask your pharmacist how to dispose of used injection pens properly to protect the environment.
Keep Plegridy and all medicines out of the sight and reach of children. If you are unsure how long a pen has been outside the refrigerator, discard it and use a new one.
What Does Plegridy Contain?
The active substance in Plegridy is peginterferon beta-1a. Each pre-filled pen contains either 63 mcg, 94 mcg, or 125 mcg of the active ingredient in 0.5 mL of solution. The excipients include sodium acetate trihydrate, acetic acid, L-arginine hydrochloride, polysorbate 20, and water for injections.
Understanding the composition of your medication can be important, particularly if you have known allergies to specific ingredients. Plegridy is available in three strengths, each provided in a pre-filled injection pen:
| Strength | Pen Colour | Volume | Use |
|---|---|---|---|
| 63 mcg | Orange | 0.5 mL | Starter pack – Day 0 |
| 94 mcg | Blue | 0.5 mL | Starter pack – Day 14 |
| 125 mcg | Grey | 0.5 mL | Maintenance – every 14 days from Day 28 |
The excipients (inactive ingredients) in Plegridy are:
- Sodium acetate trihydrate and acetic acid – buffer system to maintain pH stability
- L-arginine hydrochloride – stabiliser for the protein structure
- Polysorbate 20 – surfactant to prevent protein aggregation
- Water for injections – solvent
Plegridy contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially “sodium-free.” The solution should be clear and colourless. Air bubbles may occasionally be visible in the viewing window – this is normal and does not affect the dose.
Plegridy is manufactured by Biogen Netherlands B.V. (Badhoevedorp, Netherlands) and FUJIFILM Diosynth Biotechnologies Denmark ApS (Hillerød, Denmark). The marketing authorisation holder is Biogen Netherlands B.V.
Frequently Asked Questions About Plegridy
Plegridy (peginterferon beta-1a) is used to treat relapsing-remitting multiple sclerosis (RRMS) in adults aged 18 years and older. It reduces the frequency of relapses and slows the progression of disability associated with MS. It is not a cure for MS but helps manage the disease by modulating the immune system to reduce the inflammatory damage to the central nervous system.
Plegridy is injected subcutaneously (under the skin) once every 14 days (every other week). Treatment starts with a gradual dose increase: 63 mcg on day 0, 94 mcg on day 14, then 125 mcg every 14 days from day 28 onwards. Try to inject on the same day and at the same time each dosing period for consistency.
The most common side effects of Plegridy are flu-like symptoms including headache, muscle pain, joint pain, chills, fever, and fatigue. Injection site reactions (redness, itching, pain) are also very common. These side effects are most prominent at the start of treatment and typically decrease over time. Taking paracetamol or ibuprofen 30 minutes before injection can help manage flu-like symptoms.
Plegridy should be stored in a refrigerator at 2–8°C in its original packaging to protect from light. It must not be frozen. If needed, Plegridy can be kept at room temperature (up to 25°C) for up to 30 days total, protected from light. It can be taken in and out of the refrigerator multiple times, but the total time outside the fridge must not exceed 30 days.
If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before using Plegridy. Your doctor will discuss the benefits and risks with you. Regarding breastfeeding, no harmful effects on breastfed newborns or infants are expected, and Plegridy can be used during breastfeeding.
If you miss your scheduled dose of Plegridy, inject as soon as you can and then continue with your regular schedule. However, you should not inject more than once within a 7-day period. Do not use two injections to make up for a missed dose. Maintaining a consistent every-14-day schedule is important for optimal treatment effectiveness.
References
- European Medicines Agency (EMA). Plegridy – Summary of Product Characteristics. Available at: ema.europa.eu/en/medicines/human/EPAR/plegridy. Last updated 2025.
- Calabresi PA, Kieseier BC, Arnold DL, et al. Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014;13(7):657–665. doi:10.1016/S1474-4422(14)70068-7
- Newsome SD, Kieseier BC, Arnold DL, et al. Subgroup analyses of ADVANCE: a phase 3 study of peginterferon beta-1a in relapsing-remitting multiple sclerosis. J Neurol. 2016;263(5):871–880. doi:10.1007/s00415-016-8042-9
- Hu X, Shang S, Engel M, et al. Long-term efficacy and safety of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis: ATTAIN extension study. Mult Scler Relat Disord. 2021;49:102761. doi:10.1016/j.msard.2021.102761
- Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777–788. doi:10.1212/WNL.0000000000005347
- National Institute for Health and Care Excellence (NICE). Multiple sclerosis in adults: management. NICE guideline [CG186]. Updated 2022.
- World Health Organization (WHO). Atlas: Multiple Sclerosis Resources in the World 2008. Geneva: World Health Organization.
Editorial Team
This article has been medically reviewed by the iMedic Medical Review Board, which includes board-certified specialists in neurology, clinical pharmacology, and internal medicine. All medical claims are supported by peer-reviewed evidence and current international guidelines (EMA, AAN, NICE, WHO).
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