Disease Modifying Treatments
Treatment of Acute Relapses
Acute relapses are usually followed by spontaneous remission (improvement) over 1-3 months depending on the severity.
For mild relapses, symptoms are usually simply monitored to ensure recovery.
Severe relapses causing significant disability (especially if affects mobility) may necessitate presentation to the emergency department and admission for treatment and physiotherapy/rehabilitation.
High dose Methylprednisolone (anti-inflammatory) can speed up remission but doesn’t change the degree of recovery (ie partial vs complete recovery) so it is generally reserved for relapses that cause significant disability. It is given intravenously either in hospital (if needing admission) or the first dose in the emergency department or infusion centre with nurses visiting the home for the subsequent two doses.
Most common side effects are insomnia, heartburn and mood changes (see full product information).
Preventative treatment of Multiple Sclerosis with active inflammation
These treatments are proven to reduce the frequency of acute relapses and prevent new lesions appearing on MRI. They don’t treat current symptoms or repair lesions.
There are currently many treatment options available that are subsidised by the PBS. There is no “best treatment” or single treatment algorithm.
Treatment is best individualized in terms of :
- Tolerability ie. Self-injections vs orals vs hospital-based treatment
- Frequency of treatment ie. How often you need a particular treatment
- Efficacy ie. Concern about the disease causing disability (hospital-based infusions are the most effective treatment)
- Risks ie. Concern about potentially serious side effects of treatment (self-injectables are the safest treatment)
Generally MS specialists recommend:
- Starting treatment early (ie. before significant disability has occurred).
- Use a treatment that the patient is prepared to take and tolerates.
- Balancing efficacy and safety of the treatment. This is a shared decision between patient and doctor.
- Monitor closely (clinically and MRI) to ensure the chosen treatment is controlling the disease adequately.
- Switch to a more effective treatment if there is evidence of ongoing disease activity.
The following list of therapies is provided as a brief overview to help facilitate decision making rather than a full description of each medication. Mechanism of action, results of clinical trials and a full list of adverse events are described in the product information (“PI”). Also please feel free to ask your neurologist and MS nurse for further information.
Modulate (“calm”) the immune system rather than being immunosuppressive.
Pros: Good and well defined long-term safety profile owing to their 15+ year history in widespread clinical use.
Cons: Modest efficacy.
1. β Interferons
Various formulations available ranging from once every 2 weeks subcutaneous (Plegridy), once/week intramuscular (Avonex), 3 times per week subcutaneous (Rebif) or every second day subcutaneous (Betaferon).
Most common side effect is flu-like symptoms (muscle aches, headaches) for about 24 hours after each injection. Typically wears off over the first few months. Few serious safety concerns.
Tip: Titrate dose up slowly and use paracetamol or ibuprofen prior to injection to minimize flu-like side effects.
2. Glatiramer Acetate
Daily or 3 times per week subcutaneous (Copaxone).
Most common side effect is injection reaction such as pain and redness. Few serious safety concerns.
Tip: Ensure medication is at room temperature prior to administration to minimize injection reactions.
More immunosuppressive (lead to less circulating immune cells).
Main Pro: Not injections! Easy for travel (don’t require refrigeration). Gilenya, Tecfidera and Mavenclad are probably more effective than the self-injectables.
Cons: More potential safety concerns than self-injectables (although Aubagio has a better safety profile than the other oral treatments).
1. Fingolimod (Gilenya)
Generally well tolerated. Routine monitoring (6 hours) of heart rate and blood pressure required following first dose due to transient effect on heart rate, and routine eye check 3-4 months after the first dose to exclude macular oedema (swelling at the back of the eye). Both rare in otherwise healthy individuals. Regular blood tests required to monitor blood counts (lymphocytes typically reduced to 0.3-0.7) and liver function.
Tip: Avoid live vaccinations during treatment. You can still receive the influenza vaccine.
2. Dimethylfumarate (Tecfidera)
Most common side effect: Flushing and gastrointestinal side effects common in first 2-4 weeks but generally improves with time. Regular blood tests required to monitor blood counts, liver and renal function.
Tip: Take in the middle of a substantial meal to minimize side effects.
3. Teriflunomide (Aubagio)
Less effective than Gilenya but better safety profile.
Generally well tolerated. Potential teratogenic effect on foetus. Therefore need to ensure adequate contraception. Not usually recommended for women in the reproductive age group. Regular blood tests to monitor blood counts and liver function.
Tip: Medication can be rapidly eliminated using cholestyramine.
4. Cladribine (Mavenclad)
Daily for 4-5 days then 2nd course (daily for 4-5 days) one month later (week 5) followed by further 2 courses 12 months later. Further yearly treatments as required.
Generally well tolerated. Regular blood tests required to monitor blood counts.
Tip: Avoid live vaccinations during treatment. You can still receive the influenza vaccine.
More immunosuppressive than oral therapies (although Natalizumab only suppresses the immune cells within the central nervous system). These therapies can only be given in a hospital infusion centre as an outpatient.
Main Pros: highly effective
Main Cons: More potentially serious side effects (both known and unknown).
1. Natalizumab (Tysabri)
Monthly single intravenous infusions
Generally well tolerated. Rare side effect of PML (progressive multifocal leukoencephalopathy), a brain infection caused by the JC virus (average 1:1000). Regular blood tests to check blood counts and liver function.
Tip: Check for JCV serology prior to and during treatment with Tysabri every 6 months to estimate risk of PML (risk higher if JCV positive and much lower if JCV negative).
2. Alemtuzumab (Lemtrada)
Two courses of intravenous infusions, 12 months apart (first course is daily infusions for 5 days, the second course is daily infusions for 3 days).
Most common side effects early on are infusion reactions (rash, fever, headache). Main concerns are the risk of infection and the development of other autoimmune disease over time (mostly thyroid disease but potentially more serious bleeding and kidney disorders). Monthly blood and urine tests to monitor blood counts, thyroid and kidney function for at least 5 years (regardless of ongoing treatment).
Tip: Premedication helps to reduce infusion reactions and prophylactic anti-viral for one month reduces the risk of cold sores.
3. Ocrelizumab (Ocrevus)
– First dose split into 2 infusions given 2 weeks apart followed by single 6-monthly intravenous infusions.
– Most common side effects early on are infusion reactions (rash, fever, headache). Main concerns are the risk of infection.
– Tip: Premedication helps to reduce infusion reactions.
4. Hematopoietic Stem Cell Transplantation (HSCT)
HSCT appears to be a very effective treatment in patients with evidence of active inflammatory disease who do not respond to conventional treatment. However, some uncertainty remains regarding efficacy and safety (mortality up to 1%) due to the variability in treatment protocols and relatively small clinical studies.
(HSCT is not indicated for those with progressive MS).
Stem cells are collected from blood and re-infused following high-dose chemotherapy treatment.
Most common side-effects are infections while immunosuppressed following chemotherapy immunoablation, and the toxic effects of chemotherapy (that vary depending on the type of chemotherapy and dose used).
Treatment of Multiple Sclerosis with no evidence of active inflammation
(no relapse or contrast-enhancing lesions on MRI, including primary progressive and secondary progressive MS)
There is not currently any therapy that has proven efficacy to reduce progression of disability in the absence of active inflammatory disease.
Some MS patients are taking off-label 300mg biotin per day, available through compounding pharmacies. The evidence for this therapy is still incomplete.
Several clinical trials have recently shown some effect in various forms of progressive disease (e.g. ocrelizumab in PPMS) and a number of clinical trials are still in progress. Hopefully over the next few years treatments will be available that can protect and possibly even repair the central nervous system.
If you are intending to become pregnant or breast-feed please discuss the approach to your MS therapy with your neurologist or MS nurse. Copaxone is generally considered safe to be taken up until the time you become pregnant but other treatments should be stopped prior to trying to become pregnant. Relapses are very uncommon during the pregnancy and medication is generally not required or recommended. Medications are generally excreted into the breast milk with potential harm to the baby if absorbed. Although data is limited, injectable treatments such as Copaxone are unlikely to be absorbed.