In addition to the effects of a substance, its side effects play an important role not only in the decision for therapy, but also in the practical application of MS therapy. This article is about Teriflunomid.
Teriflunomide is a drug used to treat adult patients with relapsing-remitting multiple sclerosis. The drug was recently also approved for the treatment of children and adolescents with MS from the age of 10. The therapy is administered by taking a 14 mg tablet/day (for children and adolescents with a body weight under 40 kg with a 7 mg tablet/day). There are no specific guidelines for taking the medication. The tablet can be taken with or without food. The time of intake can be freely chosen, but should then be kept reasonably constant from day to day.
Teriflunomide is a drug with moderate anti-inflammatory efficacy. However, it has a favorable side effect profile. Therefore, it belongs together with glatiramer acetate, interferon-beta, and dimethyl fumarate to the drugs of efficacy category 1 (formerly known as basic therapy). Patients appreciate the oral administration and the simple use of the medication. Tolerance is usually very good, problems with side effects are rarely reported.
Side effects Diarrhea and Hair Loss
Of course, there are side effects that have been observed in studies and can also play a role in practice. “Diarrhea” was reported by about 15% of patients in the approval studies. However, this is not really a classic diarrhea with imperative stool urge and abdominal cramps, but the phenomenon of a thin stool. This is due to the specific (entero-hepatic) metabolism of the substance. Very few patients who observe this phenomenon suffer from it.
It is emotionally distressing for patients when they read in the package insert that a certain form of hair loss can occur. Approximately 13% of teriflunomide patients observed this phenomenon in the approval studies and only 3% in the placebo group. Even outside of the studies, patients report hair loss about 4 – 6 months after starting therapy with the substance. However, it is rarely cosmetically relevant and usually normalizes again after a short time. This is due to the fact that teriflunomide leads to a synchronization of the normally desynchronized hair cycle and many hairs that would have fallen out anyway (because they are at the end of their life cycle – telogen) fall out at the same time. This is therefore called a telogen hair loss (which can also be observed in pregnancy or after infections in a similar way). So, strictly speaking, not really a medical problem in the context of MS.
Liver value increase not relevant in practice
It is medically more relevant that teriflunomide can lead to an increase in liver values. Therefore, liver values should be checked more frequently, especially at the beginning of therapy. If no relevant change has occurred after 6 months, longer control intervals can be chosen again. From my experience, however, despite these strict requirements, there is only very rarely and if so, then only a moderate increase in liver enzymes, which can usually be tolerated. The great caution probably comes from the fact that the precursor substance of teriflunomide, namely leflunomide (approved for the treatment of rheumatoid arthritis), led to liver problems due to a different metabolic pathway. So, a noteworthy point, but rarely a problem in practice.
Monitor blood pressure
Since the effect of teriflunomide is based on a reduction of activated inflammatory cells, a slight reduction in white blood cells can be detected in some patients’ blood count. For this reason, the blood count should also be regularly checked. Furthermore, blood pressure should be monitored during therapy with teriflunomide. In clinical trials, teriflunomide has led to an increase in systolic blood pressure by an average of 2.7 mmHg. This does not sound like much, but it is quite relevant for people with high blood pressure.
Finally, a very rare side effect of teriflunomide is the occurrence of polyneuropathy. In the approval study (TEMSO), this was observed in about 2% of patients under teriflunomide, but not in any patients in the placebo group. Therefore, if corresponding symptoms occur, this rare side effect should also be considered.
Contraindicated in case of desire to have children
A final practice-relevant point is that teriflunomide is contraindicated in pregnancy due to a possible teratogenic (fetus-damaging) effect. Women of childbearing age should use strict contraception when taking teriflunomide. If a pregnancy does occur, the medication must be eliminated as quickly as possible. The fact that teriflunomide can be forcibly eliminated is possibly even a unique advantage of this substance. It can be washed out over about 2 weeks by the administration of cholestyramine or activated charcoal.
Pregnancy under teriflunomide is not an indication for a termination of pregnancy, especially if the substance was rapidly eliminated. Interestingly, in the approval study, quite a few children were born unharmed. In case of a case, the pregnancy should be accompanied by qualified ultrasound examinations.
Overall, teriflunomide is an easy-to-use moderately effective substance that enjoys good acceptance due to its characteristics, but brings with it some restrictions for women of childbearing age. However, if there is no immediate desire to have children and it is a mild/moderate MS, then teriflunomide is a well-tolerated medication without major problems in practical application. Changes from and to teriflunomide are usually well planned and unproblematic. When changing, it should be ensured that when starting a new medication or when switching to teriflunomide from another medication, the blood values have normalized again.
