Cladribine is a prodrug, which is activated after being inserted into body cells and incorporated into the DNA of cells as a so-called nucleoside analogue. This integration leads to programmed cell death. However, activation requires certain enzymatic equipment within the target cells, which is primarily found in T and B cells, which is why these immune cells are primarily attacked by cladribine. This fact makes the drug an interesting approach in immunology. In Germany, Cladribine is sold under the trade name Mavenclad® by Merk.
Cladribine is approved for the treatment of adult patients with (highly) active relapsing multiple sclerosis. Due to its study data, the drug is considered a more effective MS preparation. In the current treatment guidelines, it is classified in efficacy category 2.
Pulsed Immunotherapy
The approved dose is 3.5 mg/kg body weight. Therefore, cladribine is used in a weight-adapted manner (unlike many other MS drugs). Another special feature of cladribine is its use as pulsed immunotherapy. This means that the first half of the dose (1.75 mg/kg KG) is given on each of 5 days in the 1st and 2nd months of the 1st treatment year. Then there is a break until the start of the 2nd treatment year. At the beginning of this, the other half of the total dose is administered in the same way. After completing these two treatment phases, no further treatment with cladribine is necessary in years 3 and 4. Although a resumption of therapy from the 4th year has not been studied, it can be considered (according to expert opinion) in the event of recurrence of disease activity.
For patients, this regimen of pulsed immunotherapy means that cladribine tablets must be taken on 20 days. Due to its convenience, the therapy is an interesting option for patients.
It is also interesting that Cladribine has been used in medicine for a long time. The substance was originally developed for chemotherapy of hairy cell leukemia, a rare form of blood cancer. Because of this history as a chemotherapeutic agent, some patients are suspicious. In addition, more tumors were recorded in the treatment group in the approval study, so the approval process was primarily stopped. Even if it has now been shown that the tumor risk for cladribine is not higher than that of other immunotherapeutics, this past sticks to the preparation.
Monitoring White Blood Cells
In actual use, however, it can be noted that cladribine is a fairly well-tolerated and easily applicable medication. The main side effect of cladribine is based on its mode of action on T and B cells. After ingestion, there is a drop in white blood cells, which then recovers over the course of the year. In rare cases, there is a very significant drop in white blood cells, which may require further precautions.
As a rule, most patients tolerate taking cladribine without side effects. Some patients report fatigue and lethargy during intake, rarely nausea and diarrhea are reported. Skin redness (e.g. in the décolleté) is occasionally reported. In the studies, a more frequent occurrence of herpes (re) infections was observed, although this only affected approx. 3% of the study participants. However, this can also be observed in use. So before starting treatment, not only is it necessary to ensure sufficient immunity against chickenpox viruses, but also to consider vaccination against Herpes Zoster. Even if this is recommended by the STIKO for patients with immunotherapy from the age of 50.
Another important topic is pregnancy: Since cladribine interferes with DNA synthesis, malformations are to be expected. Animal experimental studies have also shown reproductive toxicity. Women of childbearing age must use a reliable method of contraception during treatment with cladribine and for at least 6 months after the last dose to prevent pregnancy. Male patients must also take precautions during treatment with cladribine and for at least 6 months after the last dose to prevent pregnancy in their partner. Breastfeeding is also contraindicated during treatment with cladribine and 1 week after the last dose. On the other hand, pulsed immunotherapy enables the planning and realization of the desire to have children in year 3 and 4 after first intake.
If these restrictions are observed, cladribine is a well-tolerated and effective medication for the treatment of relapsing MS, which is particularly characterized by its low therapy and monitoring burden.
