In 2017, the European Medicines Agency approved tofacitinib for the treatment of ulcerative colitis in adult patients who presented an intolerance, insufficient response or loss of response to conventional treatment or biological medical products (such as infliximab, adalimumab, golimumab or vedolizumab), which are also commonly administered to treat ulcerative colitis.
Tofacitinib’s mechanism of action is different to all other currently approved molecules: it inhibits a route of inflammation known as JAK (Janus kinase). Inhibiting this route of action represents a new approach in the treatment of ulcerative colitis.
This treatment has many advantages in terms of its administration: it is administered orally, and this encourages patients to accept and follow the treatment. Furthermore, it has a fast onset of action, the effect of the drug only lasts for a few hours in the body, there is no risk of producing antibodies against it and it is used in monotherapy, in other words, there is no need to combine it with other drugs.
The dose used is 10 mg every 12 hours for 8 weeks. If there is an improvement in the symptoms and reduced inflammation is detected by the endoscopy, the dose should be reduced and tofacitinib should be used as maintenance therapy. If after 16 weeks there is no benefit obtained from using the drug, treatment should be suspended.
The drug’s safety profile is favourable. However, there are various risks that should be taken into consideration before deciding whether tofacitinib should be administered to the patient. On the one hand, the treatment is associated with a greater risk of presenting infections, particularly herpes zoster, although this tends to be a mild infection that can be treated with oral antivirals, and does not require suspension of the drug. On the other hand, and as was demonstrated by a recent study with the participation of Hospital Clínic, special precaution should be taken when administering tofacitinib in patients at high risk of thromboembolism. These patients are those who have a history of deep vein thrombosis, pulmonary thromboembolism, cancer, hereditary coagulation disorders, or who take combined hormonal contraceptives. It has been observed that there is an increased risk of thromboembolic disease emerging in these cases. For this reason, patients aged over 65 years are advised to use tofacitinib only when there is no other therapeutic alternative.
Currently, the data for use in pregnant women, or women who are breastfeeding, is very limited. For this reason, the recommendation is for these women to avoid tofacitinib for now. There are no restrictions in men who wish to have a child. Nevertheless, performing analytical controls both at the start of treatment and periodically is advised in all cases where tofacitinib is administered, in order to detect any emergence of side effects.
The objective of treatment in patients with ulcerative colitis is to control the symptoms of the disease. Once this has been achieved, the long-term objective is to prevent new flare-ups of the disease, which is why maintenance therapy is required. There are various drugs available that can meet this objective, but even so there is a group of patients in whom the disease cannot be controlled. For them, the new treatment with tofacitinib could be an effective solution.
Author: Dr Agnès Fernández, gastroenterology specialist at the Clínic Institute for Metabolic and Digestive Diseases