Clinical Edge Journal Scan

Commentary: Concerning PsA treatments and comorbidities, March 2023

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

Author and Disclosure Information


Vinod Chandran, MBBS, MD, DM, PhD

Psoriatic arthritis (PsA) is a heterogeneous disease with clinical manifestations affecting the skin, joints, spine, and periarticular structures, such as the entheses and tendons. The impact of these manifestations individually on health-related quality of life (QOL) and physical function is less studied. Using data from a cross-sectional observational study including 2222 patients with a physician-confirmed diagnosis of PsA, Walsh and colleagues report that the presence of enthesitis, dactylitis, inflammatory back pain, and peripheral joint involvement was significantly associated with worse QOL and self-rated health when compared with patients without these manifestations. Moreover, an increasing number of affected joints and greater body surface area with psoriasis were significantly correlated with poorer functional state and greater work productivity impairment. This study provides further insights into the effect of the different domains of PsA on the patient. Clinicians managing PsA should therefore evaluate these domains and aim to reduce disease activity in each domain to improve QOL and function.

With regard to advanced targeted therapies, there is concern about the side effects of Janus kinase (JAK) inhibitors, especially in patients with comorbidities. To address safety concerns with upadacitinib, a selective JAK1 inhibitor, Burmester and colleagues conducted an integrated safety analysis of 12 phase 3 trials that included 6991 patients (PsA n = 907; rheumatoid arthritis [RA] n = 3209; ankylosing spondylitis n = 182; and atopic dermatitis n = 2693) who received upadacitinib (15 or 30 mg once daily). Some trials included active comparators; therefore, safety among 1008 patients (RA n = 579; PsA n = 429) who received 40-mg adalimumab every other week and 314 patients with RA who received methotrexate were compared with those treated with upadacitinib. Overall, patients with PsA receiving 15-mg upadacitinib once daily had acceptable rates of treatment-emergent adverse events (TEAE; 244.8/100 patient-years [PY]), serious TEAE (11.1/100 PY), TEAE leading to discontinuation (5.4/100 PY), and death (0.8/100 PY). Patients with PsA treated with upadacitinib had higher rates of herpes zoster, nonmelanoma skin cancer, and elevations in creatine phosphokinase when compared with patients treated with adalimumab. Although these results are reassuring to clinicians treating PsA, continued surveillance regarding the risks for venous thrombosis, cardiovascular events, and cancer are required.

In a post hoc analysis of 10 clinical trials that included patients with PsA (n = 783) and psoriasis (n = 3663) who received tofacitinib, Kristensen and colleagues reported that the risk for major adverse cardiac events was higher among patients with PsA and a high 10-year atherosclerotic cardiovascular disease (ASCVD) risk vs patients with a low ASCVD risk. The incidence of cancer was highest in patients with PsA and an intermediate 10-year ASCVD risk. Although these studies are reassuring, the assessment and risk stratification of adverse events with JAK inhibitors and therapies in PsA will require longer-term comparative clinical trials as well as an evaluation of observational data from disease registries.

Comorbidities also have an impact on treatment persistence in PsA. Tillett and colleagues conducted a retrospective study including 9057 patients with plaque psoriasis alone or with concomitant PsA who received either ustekinumab or conventional systemic disease-modifying antirheumatic drugs. They demonstrated that among patients receiving ustekinumab, those with concomitant PsA had a higher comorbidity burden, including diabetes, hypertension, and obesity, and a shorter time to ustekinumab discontinuation when compared with those with psoriasis alone. Secondary failure of advanced therapies is increasingly noted in the management of psoriatic disease. Female sex, depression, previous exposure to biologics, and the presence of comorbidities are important risk factors. Comprehensive management of psoriatic disease should include appropriate management of comorbidities for better long-term treatment persistence and outcomes.

Recommended Reading

New influx of Humira biosimilars may not drive immediate change
MDedge Rheumatology
Expert offers caveats to perioperative antirheumatic drug guideline
MDedge Rheumatology
What’s holding back physicians from prescribing biosimilars? Four specialties weigh in
MDedge Rheumatology
Treating nail psoriasis: Intralesional injections and biologics
MDedge Rheumatology
Isolated nail psoriasis may bring arthritis into play
MDedge Rheumatology