AT EULAR 2023
MILAN – Safety considerations, particularly regarding the use of Janus kinase (JAK) inhibitors, are of utmost importance in the 2023 update to recommendations for managing psoriatic arthritis (PsA) by the European Alliance of Associations for Rheumatology (EULAR). Additionally, the selection of therapy should now take into account the complete clinical presentation, explicitly considering nonmusculoskeletal manifestations.
Dr. Laure Gossec
Safety considerations with JAK inhibitors
Expanding on the existing six overarching principles from the 2019 recommendations, the PsA EULAR recommendations now introduce a seventh principle: “The choice of treatment should consider safety considerations regarding individual modes of action to optimize the benefit-risk profile.”
This addition was prompted by recent safety data on JAK inhibitors, which revealed serious potential side effects, such as heart attacks, blood clots, cancer, and severe infections, that recently prompted the European Medicines Agency to restrict their use. As indicated by the new principle, safety considerations have been incorporated into several recommendations.
For instance, in the context of peripheral arthritis, JAK inhibitors may now be considered if there is an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate, sulfasalazine, or leflunomide, and at least one biologic DMARD (bDMARD).
Alternatively, JAK inhibitors may be utilized when bDMARDs are not suitable for other reasons. However, EULAR now emphasizes caution whenever JAK inhibitors are mentioned. Specifically, “careful consideration is necessary for patients aged 65 or above, current or past long-time smokers, individuals with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, those with other malignancy risk factors, or individuals with a known risk for venous thromboembolism.”
Consider nonmusculoskeletal manifestations in treatment decisions
In another significant update, EULAR now recommends that the choice of therapy should also consider nonmusculoskeletal manifestations associated with PsA. “There is a notable shift in perspective here,” Dr. Gossec told this news organization. Clinically relevant skin involvement should prompt the use of IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitors, while uveitis should be treated with tumor necrosis factor (TNF) inhibitors.
In the case of inflammatory bowel disease, EULAR advises the use of anti-TNF agents, IL-12/23 or IL-23 inhibitors, or a JAK inhibitor. The recommended course of action within each treatment category is not ranked in order of preference, but EULAR emphasizes the importance of following EMA recommendations and considering safety.
Systemic glucocorticoids removed
Certain medications have been removed from the recommendations, reflecting the heightened focus on treatment safety. The use of systemic glucocorticoids as adjunctive therapy is no longer recommended. “We always had reservations about their use, and now we have eliminated them. We are aware that they are still utilized, with 30% of patients in Germany, for instance, receiving low doses of glucocorticoids. However, the long-term efficacy/safety balance of glucocorticoids is unfavorable in any disease, particularly in patients with psoriatic arthritis and multiple comorbidities,” Dr. Gossec explained.