Glatiramer acetate
Summary: Glatiramer acetate (GA) has been the other injectable workhorse of MS treatment for decades. It is moderately effective with only a minority of MSers achieving long-term NEDA and the impact on end-organ damage (brain volume loss) is only modest. In general GA formulations are relatively well tolerated in the short-term with the main issues being injection site reactions, occasional flushing reactions with tightness of the chest, swelling of lymph nodes and rarely urticaria or hives. However, long-term use of GA leads to lipoatrophy (loss of fatty tissue under the skin). A big plus is that it has no monitoring requirements and it is safe in pregnancy. Adherence is been a problem in the long-term due to injection fatigue. With more effective DMTs to choose from, with other more favourable attributes, most MSers now tend to choose non-injectable treatments. Despite this there is still a role for GA in the treatment of MS, in particular in women who are planning to start or extend their families.
Trade Names: Copaxone-20 (Teva), Copaxone-40 (Teva), Brabio-20 (Mylan), Brabio-40 (Mylan)
Mode of action: Immunomodulatory. GA is often referred to as the DMT with 9 or more modes of action, because so many different effects on the immune system have been linked to its mode of action. Importantly, none of these immunological changes are associated with immunosuppression.
Efficacy: Moderate
Class: Maintenance, immunomodulatory
Immunosuppression: No
Posology:
- GA-20 (Prefilled syringe 20mg.mL sc daily)
- GA-40 (Prefilled syringe 40mg/ml sc 3x per week)
Main adverse events: Injection site reactions are the most frequent adverse reactions with redness, pain, itching, swelling and rarely breakdown of the skin. WIth prolonged injecting lipoatrophy may occur. and skin necrosis. Occasionally MSers may experience an immediate reaction post injection with flushing, chest tightness, shortness of breath, palpitations and a rapid heart rate.
Adverse events of special interest:
- Swelling of lymph nodes (pseudolymphoma)
- Urticaria or hives
Neutralizing Antibodies (NAbs): No
Pharmacovigilance monitoring requirements:
- Baseline: None
- Follow-up: None
Rebaselining: A rebaseline MRI needs to be done after GA has had sufficient time to work. I would recommend ~7-12 months after starting treatment and to include Gd-enhancement as part of the MRI. GA is the one maintenance DMT that takes quite a long time for it to reach maximum effectiveness on MRI. The presence of Gd-enhancing lesions on the rebaseline scan is sufficient evidence at this stage to switch/escalate treatment to another DMT.
Pregnancy: No known reproductive toxicity. Generally considered to be safe in pregnancy. In case of unplanned pregnancy on GA termination of the pregnancy is not necessary. Most neurologists are recommending continuing GA treatment throughout pregnancy.
Breastfeeding: Safe, not contraindicated.
Male Fertility: Safe
Vaccination: Safe
Summary of Product Characteristics (SmPC): Copaxone-20, Copaxone-40, Brabio-20, Brabio-40