International experts recall the proper use of JAK inhibitors (JAKI)

During the development of JAK inhibitors (JAKI) in an ever wider field of chronic immuno-inflammatory diseases. In addition, various signals concerning their tolerance were mentioned in literature. Furthermore, First good practice recommendations have just been published by a panel of European experts. Nevertheless, In 2022. In addition, the data ofORAL Surveillancestudy carried out in rheumatoid arthritis, put a spotlight on the thromboembolic and cancerous ride linked to tofacitinib. In addition, Since then. Therefore, other drugs targeting JAK have obtained new indications, with their procession of clinical data and long -term monitoring data or register. Nevertheless, So much data that motivated theupdating this consensus, which appeared In Annals of the Rheumatic Diseases. If it has been published in a journal intended for rheumatologists. international experts recall proper use it has been established by experts from the various disciplines concerned and therefore wants to address them transversely. So. ” It does not deal with the way in which a particular disease must be taken care of, but rather the way in which the Jaki must be used once the decision has been made To prescribe them as part of their indications.

Update of contraindications – International experts recall proper use

The question of precautions. contraindications constitutes a central element of the text, since it has been at the heart of the debates since oral surveillance. Thus, 6 major situations are mentioned as at risk:

• Severe active or recurrent infections, including tuberculosis and opportunistic infections: the term here introduces to ” recurring Aims to replace the concept of chronicity of the previous text;
• Personal history and cancer international experts recall proper use diagnosis: consensus is expanding contraindications to history, following data from the oral surveillance study which showed an increase in certain cancers, in particular pulmonary, in smoking patients treated with Tofacitinib versus His comparator. The data from the registers do not show an increase in cancer outside that of non -melanocytic skin cancer. but longer -term follow -up studies are necessary;
• Chronic advanced liver disease decompensated or severe renal damage (creatinine clearance <30 ml/min);
• Pregnancy and breastfeeding remain maintained as a contraindication in view of the teratogenicity data obtained in animals;
• The history of thromboembolic events no longer only concern venous events, but also arterial, in view of the data accumulated since 2021;
• Vaccination by an attenuated living vaccine was added this year.

Adverse effects monitoring

The text identifies 5 main categories international experts recall proper use of undesirable effects that should be identified:

• severe and opportunistic infections, including tuberculosis and zona, as the 2019 text already pointed out;
• Cancers, including non -melanocytic skin tumors, even if there is still lack of data confirming the first register studies;
• Hematological complications (lymphopenia, neutropenia, thrombocytopenia, anemia), anemia being mainly linked to the inhibition of JAK2;
• Venous thromboembolic events, which were mentioned for high tofacitinib or baricitinib dosages, are considered to be dose-dependent and linked to all Jaki;
• Non -specific biological anomalies are mentioned for different drugs (elevation of CPK, creatine, appearance of acne for jaki outside Filgotinib, etc.).

Prétherapeutic evaluation and monitoring

The text strengthens and updates its messages concerning the importance of the pre -therapeutic evaluation:

• Systematic analysis of risk factors for international experts recall proper use major undesirable events (major unwanted cardiac events, venous thromboembolic events, infection history, zona, viral hepatitis, complicated diverticulitis, etc.);
• skin examination in order to detect skin cancers in risky subjects;
• Thromboembolic risk assessment: both cardiovascular and tumor risk;
• History tobacco history;
• Basic biological assessment (Numeration, liver blood tests, renal function and lipid levels), other tests that can be necessary depending on the history or the appearance of clinical signs;
• Screening: VHB, HCV, search for hepatitis D among carriers of VHB, HIV in subjects at risk, tuberculosis;
• vaccination status.

Finally. concerning monitoring, experts insist on the importance of assessing the activity of the disease with tools excluding the use of inflammatory markers (CRP, VS): indeed, the mechanisms of action of Jaki (especially on IL-6) can lead to a decrease in their international experts recall proper use circulating rate, disconnected from the real clinical improvement linked to the drug. Finally. they are now talking about surveillance ” periodic Hematological, hepatic, renal, lipid and skin examinations rather than proposing specific frequencies, in order to adapt to the specific recommendations of the treated pathology and those in progress in the country.