This time it’s about teriflunomide, which is known under the trade name Aubagio. The immunotherapy is used for mild to moderate courses of relapsing forms of MS.
Teriflunomide also has a broader mechanism of action and is one of the immunomodulating drugs. Please remember that I can only provide an overview here. Ask your neurologist and MS nurse for detailed advice on choosing the right therapy for you. They should know your complete state of health and be aware of your goals, wishes, fears and preferences.
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Table of Contents
General Information
To get a good overview of the major topic of therapy decisions, I recommend that you first listen to episode 58: Immunotherapy in MS. A guide to efficacy and choice with Prof. Tjalf Ziemssen. There you will find out why:
- You can only compare the various disease-modifying drugs to a limited extent.
- It is important to start an effective therapy quickly.
- MRI and other examinations are important for assessing progression and provide information about effectiveness.
- Therapies should be changed as little as possible, but of course if they are not effective enough.
- In most cases, it is better to start with a highly effective therapy and only switch to a lower category at an advanced age.
- In the case of highly active MS, it may be more important to start immunotherapy quickly and tackle rehabilitation as a second step.
- Generics and biosimilars are being used more and more and which approval requirements they have to fulfill.
- The risks and side effects of a therapy must be differentiated into unpleasant side effects at the start of therapy and rare possible risks. And these must be set in relation to the usually irreversible effects of untreated MS in the long term.
- It is important to honestly discuss your opinion, wishes, goals and fears with your neurologist in order to make treatment decisions together that both sides can agree on.
- It is advantageous to be cared for by MS specialists and to stay informed yourself in order to benefit from new findings and treatment options.
- Contribute to a favorable prognosis with your own healthy lifestyle.
Another general note
The approval studies for the individual drugs were carried out at very different times. Thirty years ago, you had to be more severely affected or more advanced in the course of the disease to receive a reliable diagnosis of multiple sclerosis. Less severely affected people were probably not diagnosed or not diagnosed at first. With ever-improving examination methods, such as MRI, even small lesions in the central nervous system can now be seen better. Furthermore, 30 years ago it was not yet known that neuromyelitis optica spectrum diseases, NMOSD for short, are separate diseases that require their own therapies and sometimes even react negatively to MS medication. They were previously thought to be multiple sclerosis and MS therapies did not alleviate the disease activity.
How is teriflunomide (Aubagio and generics) classified in immunotherapies?
There are currently three different therapeutic approaches for the preventive, i.e. disease-modifying therapy (DMT) of multiple sclerosis. The most unspecific is immunomodulation, which also includes teriflunomide. It becomes somewhat more specific with migration inhibition. And the most specific is the depletion of immune cells. The DMTs are listed in alphabetical order:
- Immunomodulation – the therapies weaken the immune system. They have a very broad effect via various factors (e.g. on Th1/T17 – Th2/Treg, antigen presentation) as well as on different signaling pathways and possibly via other mechanisms: they attempt to shift the milieu from inflammatory to non-inflammatory:
- Dimethyl fumarate (Tecfidera and generics) & diroximel fumarate (Vumerity),
- Glatiramer acetate (Copaxone and generics),
- Interferon-beta: interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaferon, Extavia), peginterferon beta-1a (Plegridy)
- Teriflunomide (Aubagio)
- Migration inhibition – the migration of certain immune cells is inhibited:
- Natalizumab (Tysabri, Tyruko)
- S1P modulators: Fingolimod (Gilenya), Ozanimod (Zeposia), Ponesimod (Ponvory), Siponimod (Mayzent)
- Cell depletion – developing immune cells die off
- Depletion of T-cells, B-cells, NK-cells and monocytes: Alemtuzumab (Lemtrada, Campath)
- T- and B-cell depletion: Cladribine (Mavenclad, Leustat, Litakin)
- B-cell depletion: ocrelizumab (Ocrevus), ofatumumab (Kesimpta, Bonspri), rituximab (Mabthera, Rituxan), ublituximab (Briumvi)
What is teriflunomide (Aubagio) approved for?
Teriflunomide is approved for the treatment of relapsing forms of multiple sclerosis for patients aged ten years and over. The German Multiple Sclerosis Competence Network (KKNMS) and the German guideline recommend its use in mild or moderate forms of the disease.
Different information or recommendations are possible from country to country.
What is the situation for special patient groups?
Children and Teenagers
Teriflunomide (Aubagio) is approved for children aged ten years and older. Please contact an MS specialist, preferably a neuropaediatrician, for individual advice.
Pregnancy and Breastfeeding
There is no approval for pregnant women. The drug was teratogenic in animal experiments.
In the approval studies of teriflunomide (Aubagio), there were 70 pregnancies among multiple sclerosis patients and a further 152 pregnancies that occurred after approval. A normal malformation rate of 3.6% occurred in these 222 pregnancies. The miscarriage rate was 21.2%.
Teriflunomide passes into the sperm of men in very small quantities. The resulting risk of damage to the fetus is considered low. Two smaller evaluations from Denmark and the company’s own safety database with pregnancies exposed to teriflunomide via the father showed a probability of 4.5%-5.6% of the occurrence of minor malformations, which is not considered to be increased compared to the general population.
In individual cases, a rebound effect was observed after discontinuation of teriflunomide (Aubagio) outside pregnancy. However, no major studies have been carried out to date. Therefore, please discuss with your neurologist whether you should start a different immunotherapy after washing out teriflunomide, which will take you up to the onset of pregnancy.
Teriflunomide has been shown to pass into the milk of rats. Studies in humans are not available. However, due to the properties of the molecule, transfer is likely.
If you are pregnant or planning to become pregnant, please discuss your treatment strategy with your MS specialist.
Recommendation of the European (EMA) and American regulatory authorities (FDA)
Teriflunomide should be avoided during pregnancy and breastfeeding. Women of childbearing age should use effective contraception during therapy and discuss alternatives with their neurologist if they wish to have children. For men planning to become fathers, the FDA recommends a washout period as a precaution.
Who should avoid teriflunomide?
Persons with severe liver dysfunction and acute hepatitis. Patients with severe active infections as well as immunodeficient patients (including HIV infection) and patients with chronic infections (especially chronic viral hepatitis and tuberculosis) should also avoid teriflunomide. If bone marrow function is markedly impaired, significant anemia, leukopenia, neutropenia or thrombocytopenia is present.
Severe hypoproteinemia, severe renal insufficiency requiring dialysis and hypersensitivity to the active substance or other ingredients.
If there is a positive history of Stevens-Johnson syndrome, erythema multiforme or toxic epidermal necrolysis. In pregnancy and during breastfeeding. Therefore, efficient contraception must be continued after discontinuation of teriflunomide until plasma levels of the active metabolite fall below a certain level or until successful, possibly accelerated elimination.
How does teriflunomide works?
Among other things, teriflunomide has an effect on T and B lymphocytes. The active substance prevents T-cell maturation by quantity and inhibits B-cells in a dose-dependent manner. Inflammatory messengers are presumably reduced, specifically interleukin-6 (IL-6) and thus less microglia are activated.
How is it taken?
Teriflunomide is swallowed as a film-coated tablet containing 14 mg once a day. In children weighing < 40 kg, the dose is halved to 7 mg/day. The tablet can be taken with or without food. No other dose adjustments are made, not even in cases of mild or moderate hepatic insufficiency or renal insufficiency.
The maximum duration of therapy with teriflunomide is currently unknown. Most of the data is based on the two-year approval studies. In addition, there are patient cohorts with up to 10 years of exposure.
How effective is teriflunomide (Aubagio and generics)?
Gavin Giovannoni, an MS expert from the UK, has graded his MS selfie cards on a scale of one to ten, with one being low efficacy and ten being maximum efficacy. In his estimation, teriflunomide (Aubagio and generics) scores 2 for preventing relapss and 4 for avoiding long-term disability.
It should be noted that teriflunomide is only effective in some patients. The evaluation would therefore be shifted if only responders were rated.
In the pivotal study, teriflunomide led to 30% fewer relapses compared to placebo. In other words, you can also look at 100 patients. 46 of these patients remain relapse-free, even on placebo. In the teriflunomide group, a further 11 patients remained relapse-free. Looking at the same 100 patients, 77 remained at the same level of disability, as measured by the EDSS (Expanded Disability Status Scale), during the pivotal trial period, including the placebo group. Eleven people in the placebo group deteriorated who remained stable on teriflunomide.
Risks and side effects of teriflunomide (Aubagio and generics)
The most common side effects with teriflunomide are headache, diarrhea, increased liver enzyme levels, nausea and alopecia (hair loss). In general, these side effects, are mild to moderate in severity and subside over time. The increased liver enzyme levels might stay constantly. Normally, these side effects are no reason to discontinue treatment.
Additionally, teriflunomide might increase the risk of common infections.
Safety precautions – lab parameters
A clinical examination with medical history should be carried out every three months in the first year and every six months thereafter.
Subsequently, checks should be carried out every three months. If the absolute lymphocyte count falls below a certain level, teriflunomide must be discontinued.
In the first six months, a blood count and differential blood count should be taken every two months, then the interval can be increased to every three months.
Liver values must be checked at least every four weeks for the first six months. Patients who already have liver disease or are taking other medications that can put the liver at risk should be checked more frequently, for example every two weeks. After six months of therapy, checks every two months are sufficient. If certain liver values are repeatedly in the critical range or inflammation of the pancreas occurs, teriflunomide must be discontinued. However, the latter has occurred only rarely and is determined by an ultrasound examination of the abdomen.
Blood pressure should be checked at least every six months.
If there are clinical indications of pulmonary dysfunction, an examination by a pulmonologist should be carried out promptly.
You do not need to worry about this. It will be checked for you. However, please take the tests seriously and make up for them if you are unable to keep an appointment, and don’t skip them altogether.
On the MS selfie card mentioned earlier, the side effects are rated on a scale from one for few or rare to ten for many or frequent as follows:
- Regular side effects at six
- Long-term side effects at one
- Cancer risk at three
Teriflunomide receives the following rating in the MS Selfie Card overview of the effects of therapy:
- Clinic visits: many
- Family planning: incompatible in the short term
- Vaccinations: good response
Vaccinations
Live vaccines should be avoided and only administered after a thorough risk-benefit assessment. All other vaccinations are permitted during therapy with teriflunomide (Aubagio and generics).
The annual flu vaccination is strongly recommended.
Vaccination against herpes zoster, which leads to shingles, is recommended for patients with immunotherapy from the age of 50. In this case, vaccination with the inactivated Shingrix vaccine is recommended.
Sources
I used the following sources to create the content:
- Quality manual of the KKNMS on teriflunomide (Aubagio)
- MS-Selfie Infocards by Prof. Dr. Gavin Giovannoni
- German Multiple Sclerosis and Fertility Registry (DMSKW)
- Information from the German interview with Prof. Dr. Barbara Kornek on pediatric MS
- DMSG information on teriflunomide
- DECIMS information on teriflunomide
Final note
Please remember, there is no one great medication that helps everyone, but it must always be weighed up what suits a particular person best. Other illnesses, personal goals and preferences must also be taken into account. Your neurologist and MS nurse are the right persons to talk to and can make individual recommendations. This article is for information purposes only and does not constitute a recommendation. What helps one person may not help another.
I hope that, together with your neurologist and MS nurse, you will quickly find the right immunotherapy for you. And that you can lead a fulfilled, happy and self-determined life with MS, supported by a healthy lifestyle and a dose of fortune.
You may also want to look at the posts on the other DMTs:
- Dimethyl fumarate (Tecfidera) and diroximel fumarate (Vumerity)
- Glatiramer acetate (Copaxone, Brabio)
- Interferon-beta (Avonex, Betaferon, Extavia, Plegridy, Rebif)
See you soon and try to make the best out of your life,
Nele
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