Specialists offer insights on the use of JAK inhibitors for ankylosing spondylitis treatment
In the realm of treating Ankylosing Spondylitis (AS), a type of inflammatory arthritis that primarily affects the spine and large joints, new hope is on the horizon with the introduction of JAK inhibitors. These medications, such as baricitinib (Olumiant), upadacitinib (Rinvoq), ruxolitinib (Jakafi), and fedratinib (Inrebic), are approved for various inflammatory conditions.
However, it's crucial to note that only upadacitinib and tofacitinib have been approved for the treatment of AS. While these drugs offer potential benefits, they also come with certain risks, making them an important addition, but not a one-size-fits-all solution, to the treatment options for chronic inflammatory conditions.
JAK inhibitors work by blocking the messaging pathway that triggers the production of inflammatory proteins. This mechanism helps in managing symptoms like joint stiffening and fusion, which can make the spine rigid and inflexible in AS.
However, the use of JAK inhibitors may lead to an increase in total cholesterol levels, potentially putting individuals at risk of major adverse cardiovascular events like heart attack or stroke. Moreover, JAK inhibitors, including Xeljanz (tofacitinib), have been associated with an increased risk of serious infections, such as bacterial, viral, and invasive fungal infections.
Given these risks, it's essential to approach JAK inhibitor treatment with caution, particularly for patients over 50 years with existing cardiovascular risk factors or histories of thromboembolic events or uncontrolled lipid disorders. The Food and Drug Administration (FDA) and clinical guidelines recommend a thorough cardiovascular risk assessment before initiating JAK inhibitors in AS.
Common cardiovascular risk factors that may make a patient with AS ineligible or require cautious use of JAK inhibitors include age over 50 years combined with at least one cardiovascular disease (CVD) risk factor, pre-existing cardiovascular conditions, dyslipidemia or uncontrolled lipid abnormalities, hypertension, diabetes mellitus, smoking, obesity, and a history of ischemic heart disease or stroke.
In summary, patients over 50 with existing cardiovascular risk factors or histories of thromboembolic events or uncontrolled lipid disorders are at higher risk and may be deemed ineligible or require cautious use of JAK inhibitors for AS. Individualized cardiovascular evaluation and risk management are strongly advised before treatment.
The FDA has issued a boxed warning for Xeljanz due to serious safety risks including increased risk of heart-related events, cancer, blood clots, and death. Despite these concerns, the array of treatments available for conditions like AS gives doctors more ways to approach the condition than they have had in the past. JAK inhibitors, like tofacitinib, are being considered for treatment of other disease states, such as Still's disease, a form of juvenile rheumatoid arthritis.
References: 1. FDA Drug Safety Communication: FDA adds warnings about increased risk of serious infections, malignancies, and thrombosis with JAK inhibitors for rheumatoid arthritis and other conditions. (2021). Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-adds-warnings-about-increased-risk-serious-infections-malignancies 2. European Medicines Agency (2021). Xeljanz (tofacitinib) for the treatment of ankylosing spondylitis. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/xeljanz/information_for_the_user/pil 3. European Medicines Agency (2020). Olumiant (baricitinib) for the treatment of rheumatoid arthritis. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant/information_for_the_user/pil 4. European Medicines Agency (2019). Rinvoq (upadacitinib) for the treatment of rheumatoid arthritis. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq/information_for_the_user/pil 5. European Medicines Agency (2018). Jakafi (ruxolitinib) for the treatment of myelofibrosis. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/jakafi/information_for_the_user/pil 6. European Medicines Agency (2017). Inrebic (fedratinib) for the treatment of myelofibrosis. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/inrebic/information_for_the_user/pil
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