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Commentary: Difficult-to-Treat PsA and Medication Options, July 2024

Dr. Chandran scans the journals, so you don't have to!

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Vinod Chandran, MBBS, MD, DM, PhD

Clinical studies on psoriatic arthritis (PsA) have investigated susceptibility, severity, effect of treatment, and difficult-to-treat (D2T) disease. In a novel study, Laskowski and colleagues studied the influence of low stress resilience in adolescence on the risk for onset of psoriasis and PsA. This prospective cohort study included 1,669,422 men from the Swedish Military Service Conscription Register, of whom 20.4%, 58.0%, and 21.5% had low, medium, and high stress resilience levels, respectively, measured at conscription using standardized semistruc/;/tured interviews. Over nearly 51 years of follow-up, 9433 (0.6%) men developed PsA. Low vs high stress resilience increased the risk for new-onset PsA by 23% in the overall cohort and 53% in the subgroup of patients who were hospitalized due to severe PsA. Thus, low stress resilience during adolescence increases the risk of developing PsA later in life. The study highlights the psychological vulnerability of patients with psoriatic disease and the need for addressing psychological well-being when managing PsA.

A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.

Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.

Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.

Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.

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