Last updated on November 18th, 2025 at 06:25 pm
Summary
Teriflunomide is a moderately effective platform therapy for treating active MS; it reduces the relapse rate by ~30% and slows the acquisition of disability to a similar degree. It reduces magnetic resonance imaging (MRI) activity by ~70% and slows down brain volume loss, but not to the same degree as highly effective DMTs. Teriflunomide is licensed as a first-line therapy in the UK. It is taken as a daily 14 mg tablet. Although teriflunomide inhibits cell proliferation, it is not an immunosuppressive agent and is classified as an ‘immunomodulatory therapy’.
Teriflunomide has not been associated with opportunistic infections, secondary malignancies, a blunted antibody response to vaccines or lymphopaenia (low lymphocyte counts). Low lymphocyte counts occur in only a small minority of people with MS. In general, teriflunomide is well tolerated, with only a small number of people with MS (< 5%) developing abnormal liver function tests or gastrointestinal symptoms (mainly diarrhoea) that result in them having to stop the therapy. Teriflunomide can cause mild hair thinning that is transient; please note this is not alopecia or baldness and, in my experience, is not a problem for people with MS taking the drug.
Teriflunomide is considered to be potentially teratogenic, i.e. it has the potential to cause foetal abnormalities when women fall pregnant on the drug, which makes it unsuitable for women of childbearing age who are planning to start, or extend, their families. Teriflunomide has a long half-life and hence stays in the body for months. There is a rapid elimination procedure that can remove teriflunomide from the body within days. When teriflunomide is started, the European Medicines Agency (EMA) requires blood monitoring every 4 weeks for 6 months and 2 monthly thereafter. I think these requirements are excessive; many neurologists use the American guidelines, which stipulate monthly tests for 6 months and regularly after that.
It has been difficult to use teriflunomide in the UK, on the NHS, because of its monitoring requirements and associated costs. In clinical practice, teriflunomide seems to be much more effective than suggested by the clinical trial results, which may explain its popularity in other countries. Interestingly, people who start teriflunomide as a second-line or third-line DMT do better than those using it first-line. I have no idea why teriflunomide is more effective after people with MS have failed other DMTs; it may have something to do with its alternative modes of action, for example, its antiviral effects.
Trade name
Aubagio.
Mode of action
Teriflunomide probably has several modes of action but mainly works by inhibiting an enzyme called dihydroorotate dehydrogenase (DHODH) which affects pyrimidine metabolism in cells. This inhibits cell division, so it is called an antiproliferative agent. It is thought to work in a similar way in MS, by reducing the proliferation of activated lymphocytes. Teriflunomide also has broad-spectrum activity against many viruses.
Efficacy
Moderate. It is licensed in the UK as a platform or first-line therapy for people with active MS.
Class
Maintenance, immunomodulatory.
Immunosuppression
No.
Dosing
The recommended dose of teriflunomide is 14 mg once daily, but 7 mg/day has also been shown to be effective. In the USA, both the 7 mg and the 14 mg doses of teriflunomide are licensed. Outside the USA, only the 14 mg dose is licensed.
The 14 mg dose was superior to the 7 mg dose on several outcomes in the phase 3 trials. In general, 7 mg is prescribed to people with MS who can’t tolerate the higher 14 mg dose because of gastrointestinal symptoms or other blood abnormalities. Outside the USA, where the 7 mg tablet is unavailable, you can take the 14 mg tablet on alternate days. Splitting the tablet is not easy because it is not scored, and doing so breaks the enteric coating.
The half-life of teriflunomide is very long, so alternate-day dosing is fine. Teriflunomide can be taken with or without food.
Main adverse events
Liver
Elevations of liver enzymes have been observed on teriflunomide. These are seen within the first 6 months of treatment. People with MS with pre-existing liver disease or those who consume excessive quantities of alcohol may be at increased risk of developing elevated liver enzymes on teriflunomide.
Blood pressure
High blood pressure may occur during treatment with teriflunomide.
Infections
No increase in serious infections has been observed with teriflunomide. The safety of teriflunomide in people with MS with latent tuberculosis (TB) is unknown, which is why I recommend screening for TB infection before starting teriflunomide.
Lung
Interstitial lung disease has been rarely reported in people with MS on teriflunomide. Therefore, any new onset or worsening breathing or chest problems, such as persistent cough and shortness of breath, need to be investigated.
Blood
Teriflunomide causes a small (~15% ) drop in the number of circulating white blood cells, but not sufficient to cause any problems. In a few people with MS (<5%) the drop may be more profound and require them to stop taking the medication.
Skin
A few cases of severe hypersensitivity skin reactions have been reported on teriflunomide, including Stevens-Johnson syndrome, toxic epidermal necrolysis and a condition called DRESS (drug reaction with eosinophilia and systemic symptoms). Please look out for any skin rash.
Neuropathy
Rare cases of peripheral neuropathy have been reported in people with MS on teriflunomide. Please watch out for tingling sensations and/or loss of feeling in the toes and fingers; these adverse events tend to be symmetrical, which helps differentiate them from MS symptoms.
Neutralizing antibodies (NAbs)
NAbs are not a problem on teriflunomide because it is a small molecule and not a biological (protein) therapy.
Pharmacovigilance monitoring requirements
Baseline
Full blood count, urea and electrolytes, liver function tests, thyroid function tests, serum immunoglobulin levels, serology (varicella zoster virus, human immunodeficiency virus 1 and 2, hepatitis B and C, TB ELISpot, up-to-date cervical smear and/or human papillomavirus testing, a pregnancy test and baseline blood pressure are done.
Follow-up
Liver enzymes should be assessed every 4 weeks during the first 6 months of treatment and regularly thereafter or as indicated by clinical signs and symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, loss of appetite, or jaundice and/or dark urine. Full blood cell counts need only be performed every 6 months or if you develop an infection on treatment.
Rebaselining
A rebaseline MRI scan needs to be done after teriflunomide has had sufficient time to work. I recommend that an MRI is done 6 months after starting treatment and that Gd-enhancement is included as part of the rebaselining MRI.
Women of childbearing potential and pregnancy
If you are a woman of childbearing age, before starting teriflunomide treatment I would recommend a negative pregnancy test result. Teriflunomide is potentially teratogenic, i.e. it can cause birth defects; therefore, you must have effective contraception whilst on treatment. It takes many months to eliminate teriflunomide from the body. Therefore, on stopping treatment the potential risk to the foetus may persist, and contraception should be continued during the drug elimination period, or you should undergo the rapid elimination procedure. If there is any delay in the onset of your period (menses) or any other reason for suspecting pregnancy, you must notify your nurse or doctor immediately and undergo pregnancy testing. If pregnant, it is possible to rapidly lower the blood level of teriflunomide by instituting the accelerated elimination procedure. If you do fall pregnant whilst on teriflunomide, we would not automatically recommend termination of pregnancy but, rather, refer you to a high-risk antenatal clinic for counselling and foetal screening. Many babies exposed to teriflunomide in the womb have been born without overt problems.
Breastfeeding
Teriflunomide is excreted into the breast milk of lactating women and has the potential for adverse reactions in nursing infants, so women on teriflunomide should not breastfeed.
Fertility
There is no evidence that teriflunomide affects either male or female fertility.
Male fertility
The risk of toxicity to the embryo through teriflunomide affecting the sperm is low. Animal studies have shown no evidence that teriflunomide adversely affects male fertility or damages sperm. Despite this, some regulatory authorities have recommended that men wishing to father a child discontinue teriflunomide treatment and undergo the accelerated elimination procedure. However, the EMA does not recommend this. Based on the data, I don’t recommend that men with MS wanting to start or extend a family stop teriflunomide or take any specific precautions.
Vaccination
Two clinical studies have shown that vaccination with component or inactivated vaccines was safe and effective whilst on teriflunomide. However, the use of live attenuated vaccines may carry a risk of infections and – based on the current recommendation – should be avoided.
Travel
People with MS need to be aware that being on teriflunomide may affect travel; for example, some countries require you to be vaccinated against yellow fever, which is a live attenuated vaccine and hence contraindicated.
Summary of Product Characteristics (SmPC)
Accelerated elimination
An accelerated elimination procedure may be needed to eliminate teriflunomide from the body very quickly. This is typically done for women of childbearing age who want to fall pregnant or have fallen pregnant. It may also be done when switching treatments.
After stopping treatment with teriflunomide:
- Cholestyramine 8 g is administered three times daily for 11 days; alternatively, cholestyramine 4 g three times daily can be used but only if cholestyramine 8 g three times a day is not well tolerated.
- Alternatively, 50 g of activated powdered charcoal is administered every 12 hours for 11 days.
For women wanting to fall pregnant, the effectiveness of the accelerated elimination procedure can be verified by two tests at least 14 days apart to determine the plasma concentration of teriflunomide. Once this falls below 0.02 mg/l, a waiting period of one-and-a-half months is required before fertilisation can be advised.
Please note that cholestyramine and activated powdered charcoal may influence the absorption of oestrogens and progestogens. Since the oral contraceptive pill cannot be guaranteed reliable during the accelerated elimination procedure, an alternative contraceptive method is recommended.
Switching-2-teriflunomide
Interferon and glatiramer acetate
In general, teriflunomide can be started immediately after discontinuation of interferon or glatiramer acetate. It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide.
Natalizumab
Owing to the risk of rebound activity on stopping natalizumab, a prolonged wash-out period is not recommended before starting teriflunomide. Most often the reason for switching from natalizumab to teriflunomide, or another DMT, is to reduce the risk of carry-over PML (progressive multifocal leukoencephalopathy) from natalizumab. In our centre, we do an MRI and a lumbar puncture for cerebrospinal fluid analysis to exclude JC virus-DNA on polymerase chain reaction testing. Provided these two tests are clear, we would typically initiate teriflunomide as soon as possible after the last natalizumab infusion. We tend, however, not to use teriflunomide post-natalizumab because the data demonstrating that teriflunomide can prevent rebound activity is not as strong as for fingolimod and anti-CD20 therapies. All the recommended baseline screening tests and vaccination reviews must be done before starting teriflunomide.
S1P modulators (fingolimod, siponimod, ozanimod and ponesimod)
Because fingolimod has quite a long half-life, some neurologists recommend a short washout period, i.e. 4 ̶ 6 weeks; this may be appropriate, depending on the reason for switching. I recommend waiting for the total peripheral lymphocyte counts to go above 800/mm3 to exclude the uncommon occurrence of persistent lymphopaenia following S1P modulator administration. It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide. If you are switching because of abnormal liver function tests on a S1P modulator, you would ideally want the liver enzymes to normalise or at least drop to below three times the upper limit of normal before starting teriflunomide.
Fumarates
It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide. If lymphopaenia is the main reason for switching from a fumarate, I recommend waiting for the total peripheral lymphocyte counts to go above 800/mm3.
Alemtuzumab
It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide. I recommend waiting for the total peripheral lymphocyte counts to go above 800/mm3 before starting teriflunomide.
Anti-CD20 therapies (selective cell depleting DMTs)
It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide.
Cladribine (selective cell depleting DMT)
It is important that all the recommended baseline screening tests and vaccination reviews are done before starting teriflunomide. I recommend waiting for the total peripheral lymphocyte counts to exceed 800/mm3.
Mitoxantrone
I recommend waiting for the neutrophil and total peripheral lymphocyte counts to go above 1,000/mm3 and 800/mm3, respectively. All the recommended baseline screening tests and vaccination reviews must be done before starting teriflunomide.
HSCT
I recommend waiting for the neutrophil and total peripheral lymphocyte counts to go above 1,000/mm3 and 800/mm3, respectively. All the recommended baseline screening tests must be done before starting teriflunomide.