Glatiramer acetate: synthetic amino acid polymer as MS immunomodulator
Glatiramer acetate (brand name Copaxone, generic Brabio and others) is a synthetic polymer of the four amino acids L glutamic acid, L lysine, L alanine and L tyrosine. The mixing ratio and chain length resemble myelin basic protein (MBP). Introduced in the US in 1996 and in the EU in 2001, glatiramer acetate is among the longest established disease modifying therapies (DMT) in relapsing remitting multiple sclerosis.
Compared with modern oral therapies such as dimethyl fumarate, teriflunomide or fingolimod, glatiramer acetate is an injection therapy with a very favourable safety profile. It has no relevant effects on blood count or liver function and is considered one of the safest options during pregnancy.
Mechanism of action
The exact mechanism of glatiramer acetate is not fully understood. Hypotheses include:
- Structural similarity to MBP, competitive binding to MHC class 2 molecules and thereby blocking autoreactive T cells
- Induction of regulatory T cells (Th2 polarisation) with secretion of anti inflammatory cytokines such as IL 4, IL 10 and TGF beta
- Reduction of pro inflammatory Th1 and Th17 responses
- Possible neuroprotective effect via bystander suppression in the CNS
Clinically the result is a moderate reduction in relapse rate in relapsing remitting MS and slowing of MR activity. Compared with interferons efficacy is similar with a slightly more favourable safety profile.
Indications
- Relapsing remitting multiple sclerosis (RRMS): first line therapy in mildly to moderately active courses, alternative to interferons
- First clinical MS event (CIS): with signs of high conversion risk to definite MS
- Off label uses: rarely in other autoimmune CNS disorders, clinical data limited
Glatiramer acetate is not approved in primary progressive MS or in advanced stages of secondary progressive MS without relapses.
Dosing and administration
Standard regimen: 20 mg subcutaneously daily or 40 mg subcutaneously three times weekly (at least 48 hours between injections).
The 40 mg three times weekly regimen is preferred by many patients, since less frequent injections improve adherence.
Administration:
- Allow the prefilled syringe to reach room temperature (about 20 minutes)
- Subcutaneous injection into abdomen, thigh, hip or upper arm
- Rotate injection sites to avoid lipoatrophy
- Wash hands, disinfect skin, form a skin fold, insert needle perpendicularly
Patients are trained to self inject; many use the therapy independently at home.
Adverse effects
Very common: injection site reactions (pain, redness, swelling, pruritus), facial flushing, chest pressure, dyspnoea, palpitations, anxiety (so called immediate post injection reaction).
Common: lipoatrophy at the injection site, rash, nausea, asthenia, headache, lymphadenopathy.
Uncommon: allergic reactions, dyspnoea with bronchospasm, chills, syncope, tremor.
Rare: severe anaphylactic reactions, hepatitis, glomerulonephritis.
Immediate post injection reaction:
- Brief (5 to 30 minute) episode with dyspnoea, palpitations, chest pressure, flushing
- Occurs in up to 15 % of patients within minutes of injection
- Self limiting, no therapy needed, decreases over time
- Patients should be informed before therapy to avoid panic
Interactions
Since glatiramer acetate acts locally subcutaneously and is barely systemically available, clinically relevant interactions are scarcely known.
- Other immune therapies: combinations are rarely established outside trials
- Live vaccines: usually tolerable, since glatiramer acetate causes no marked systemic immunosuppression. Individual counselling sensible
Special considerations
Pregnancy: glatiramer acetate is considered one of the safest DMTs in pregnancy and may be used in clinical need also in the first trimester. Pregnancy registry data show no increased malformation risk.
Breastfeeding: glatiramer acetate is a polypeptide that does not pass into milk in relevant amounts because of its size. Breastfeeding under therapy is possible.
Children and adolescents: in paediatric MS, individual decision.
Allergy history: with prior systemic allergic reactions, start cautiously and inform about emergency measures.
Monitoring: clinical assessment of disease course every 3 to 6 months, MRI every 12 months. Blood count and liver tests rarely required, since glatiramer acetate barely affects laboratory values.
Patient communication: daily or three times weekly injections require discipline. Realistic information about effect (moderate relapse reduction), adverse events and the need for consistent use supports adherence. With waning adherence consider switch to oral therapy.
Related substances
- Dimethyl fumarate, oral immunomodulator in RRMS
- Fingolimod, S1P modulator in RRMS
- Inebilizumab, anti CD19 antibody in NMOSD
- Methotrexate, immunosuppressive alternative in autoimmune disease
Frequently asked questions
How exactly does glatiramer acetate act?
The exact mechanism is not fully clarified. Suggested are a shift of the T cell response from pro inflammatory (Th1, Th17) to anti inflammatory (Th2, regulatory T cells), competitive binding to MHC class 2 molecules and a possible neuroprotective effect. Clinically the result is a moderate relapse reduction in RRMS.
What is an immediate post injection reaction?
A brief, self limiting episode of flushing, dyspnoea, palpitations and chest pressure occurring in up to 15 % of patients within minutes of injection. It lasts 5 to 30 minutes and resolves without therapy. Information beforehand helps patients react calmly rather than panic.
Can I become pregnant on glatiramer acetate?
Yes, glatiramer acetate is among the safest DMTs in pregnancy. Registry data show no increased malformation risk, including with first trimester use. With pregnancy planning, therapy should be discussed with the treating neurology team.
How does glatiramer acetate differ from oral therapies?
Glatiramer acetate requires daily or three times weekly injections but has a very favourable safety profile without relevant effects on blood count, liver or kidneys. Oral therapies such as dimethyl fumarate or teriflunomide are more convenient but require regular laboratory monitoring and have specific adverse event profiles.
Sources
- EMA European Medicines Agency
- BfArM German Federal Institute for Drugs and Medical Devices
- AWMF guideline multiple sclerosis
- Gelbe Liste glatiramer acetate monograph
Legal notice and disclaimer
The information on this page is provided for general information only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace advice from a qualified physician or pharmacist. Medicines should only be used on prescription or after dispensing by a pharmacist. All information is based on the product information available at the time of writing and on recognised scientific sources; the manufacturer's current product information always prevails. Sanoliste assumes no liability for completeness, timeliness or accuracy of the information presented. In a medical emergency call the European emergency number 112.