Use of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases: safety issues

Abstract

There has been clear progress in rheumatology in recent decades with the introduction of genetically engineered biological drugs (GEBDs) as well as targeted baseline anti-inflammatory drugs, which include Janus kinase inhibitors (i-JAKs). To date, i-JAKs have been actively used and studied in various immunoinflammatory rheumatic diseases (IIRDs) – rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), as well as psoriasis, atopic dermatitis and inflammatory bowel disease. In order to summarize the accumulated experience, the experts of the European League Against Rheumatism developed a consensus, which outlined the main principles and provisions concerning the rational use of i-JAKS in patients with IIRDs. At the same time, much attention is paid to the problem of the safety of these drugs. In the present article, issues related to various aspects of the safety of the use of i-JAKs in patients with IIRDs are discussed in detail, namely: dose adjustments due to drug interactions, contraindications, pre-screening, and risk assessment. Possible adverse events related to infectious complications, malignancies, thromboembolic phenomena, and gastrointestinal perforation were analyzed. The significance of clinical and laboratory monitoring in catamnestic follow-up of patients receiving i-JAKs is emphasized. A program for further research on the mentioned problem is presented. It includes studies of the efficacy and safety of «switching» between i-JAKs in patients with poor tolerance of a particular drug or who do not respond to treatment, evaluation of the effect of i-JAKs on comorbidities including cardiovascular disease and osteoporosis, studies of the long-term safety of i-JAKs based on actual practice data, and of the effectiveness and safety of i-JAKs and GEBDs combination therapy in patients with severe RA or other conditions, etc. This consensus is designed to inform and target physicians seeking to achieve optimal use of these drugs in patients with IIRDs, as well as patients themselves and other interested parties, including facility administrators. The recommendations will undoubtedly be expanded and supplemented as new data accumulate.

Keywords

• targeted baseline anti-inflammatory drugs
• janus kinase inhibitors
• tofacitinib
• baricitinib
• upadacitinib
• filgotinib
• safety
• adverse events