Summary
Glatiramer acetate (GA) has been an injectable workhorse of MS treatment for decades, alongside the interferon-beta preparations. It is moderately effective; only a minority of people with MS receiving GA achieve long-term NEIDA (no evident inflammatory disease activity). Its impact on preventing end-organ damage (brain volume loss) is modest.
In general, GA formulations are relatively well tolerated in the short-term, 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). Major advantages are that GA has no monitoring requirements, and it is safe during pregnancy. Adherence has been a problem in the long term, owing to injection fatigue. Given that more effective DMTs are now available, with more favourable attributes, most people with MS now tend to choose non-injectable treatments. Despite this, there is still a role for GA in treating MS, particularly in women who are planning to start or extend their family.
Trade names
Copaxone, Brabio.
Mode of action
Immunomodulatory. GA is often referred to as the DMT with nine or more modes of action, because so many different effects on the immune system have been linked to it. Importantly, none of these immunological changes is associated with immunosuppression.
Efficacy
Moderate.
Class
Maintenance, immunomodulatory.
Immunosuppression
No.
Dosing
- GA-20 mg, prefilled syringe, 20 mg/mL subcutaneous (SC) daily.
- GA-40 mg, prefilled syringe, 40 mg/mL SC three times per week.
Main adverse events
Injection site reactions are the most frequent adverse events, with redness, pain, itching, swelling and (rarely) breakdown of the skin. Following prolonged injecting, lipoatrophy and skin necrosis may occur. Occasionally patients 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, ideally ~7 ̶ 12 months after starting treatment. GA is the one maintenance DMT that takes quite a long time to reach maximum effectiveness evident on MRI. I recommend including Gd-enhancement as part of the 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 while receiving GA, termination of the pregnancy is unnecessary. Most neurologists recommend continuing GA treatment throughout pregnancy.
Breastfeeding
Safe, not contraindicated.
Male fertility
Safe.
Vaccination
Safe.
Summaries of Product Characteristics (SmPC)
Copaxone 20 mg, Copaxone 40 mg, Brabio 20 mg, Brabio 40 mg
Switching-2-GA
GA-20 to GA-40 switch
People with MS may decide to switch between GA preparations because of local skin reactions. GA-40 is administered only three times per week and has demonstrated better tolerability than the daily GA-20 formulation.
Lack of efficacy
I would not recommend switching between GA preparations because of lack of efficacy or perceived lack of efficacy. If you have had a suboptimal response to one GA preparation it would make sense to switch classes. In general, I tend to escalate treatment rather than switch to another moderate efficacy DMT; vertical escalation rather than horizontal switching
Other DMTs
Provided the baseline screening blood tests are fine and there are no specific contraindications, I see no reason why GA can’t be used after any of the other licensed DMTs. However, if you are switching due to a suboptimal response, I would recommend a more efficacious DMT. There is reasonable real-life data that shows switching upwards (escalation) gives a better overall response rate than switching to a similar efficacy DMT (horizontal switching). I suspect that most people with MS who switch to GA will do so for family planning reasons, because GA has one of the best safety records in pregnancy. Another reason to switch may be an adverse event on another DMT, for example persistent lymphopaenia.
Special circumstances
The presence of other specific comorbidities may make it difficult to switch from certain DMTs to GA. These could include generalised urticaria or a known allergic reaction to GA in the past.