Patients with psoriasis appear to have the lowest risk of developing psoriatic arthritis (PsA) when they are treated with IL-23 inhibitors than with other immunomodulatory agents, according to a real-world study.
“The mechanism for PsA development is not fully understood, but it is thought to be driven by a pro-inflammatory state resulting in pathologic bone formation and turnover. Inhibition of this inflammation by immunomodulators could impede PsA progression,” said first study author Madelyn Schmidt from the University of Texas Medical Branch in Galveston, Texas, US.
Analysis of data from the TriNetX Research Network showed that among patients with psoriasis who were receiving immunomodulators (IL-12, IL-17, IL-23, TNF-alpha, JAK1, and JAK3), IL-23 inhibitors including risankizumab, guselkumab, and ustekinumab were associated with the greatest reduction in the 3-year risk of PsA. [AAD 2026, poster 71957]
In individual comparisons with risankizumab, the 3-year PsA risk was between 2- to 4-fold higher with adalimumab (hazard ratio [HR], 2.46, 95 percent confidence interval [CI], 1.97–3.08), ixekizumab (HR, 2.06, 95 percent CI, 1.54–2.76), secukinumab (HR, 2.39, 95 percent CI, 1.86–3.06), and certolizumab pegol (HR, 3.92, 95 percent CI, 2.28–6.77).
Results were similar for guselkumab and ustekinumab, with the 3-year risk estimates being higher with adalimumab (HRs, 1.42 and 1.72, respectively), infliximab (vs guselkumab only: HR, 1.46), ixekizumab (vs ustekinumab only: HR, 1.60), secukinumab (HRs, 1.55 and 1.87, respectively), certolizumab pegol (HRs, 2.19 and 1.98, respectively), and etanercept (HRs, 1.76 and 1.96, respectively).
Notably, risankizumab was associated with a lower 3-year PsA risk compared with etanercept (HR, 0.33, 95 percent CI, 0.26–0.42) and guselkumab (HR, 0.64, 95 percent CI, 0.47–0.86). A risk decrease was also observed with ixekizumab vs certolizumab pegol (HR, 0.50, 95 percent CI, 0.31–0.81).
The analysis was performed using rigorous propensity score matching. The treatment cohorts were balanced for demographics, socioeconomic factors, obesity, inflammatory bowel disease, gout, diabetes mellitus, hypertension, hyperlipidaemia, tobacco use, and alcohol-related disorders.
In light of the findings, “physicians can consider risankizumab, guselkumab, and ustekinumab as treatment options for psoriasis patients with PsA risk factors to mitigate disease progression and improve patients’ quality of life,” Schmidt concluded.
Early biologic use in youths
A separate study highlighted the importance of initiation of systemic medications that significantly lower the risk of PsA development in young people with psoriasis.
In a retrospective cohort of psoriasis patients age ≤21 years, treatment with biologics such as etanercept, ustekinumab, secukinumab, and ixekizumab was associated with around a 74-percent reduction in the risk of PsA development compared with traditional oral systemics including methotrexate, cyclosporin, and acitretin (HR, 0.263, 95 percent CI, 0.197–0.350). [AAD 2026, poster 75908]
The analysis was based on data from the TriNetX Research Platform and included 1,020 propensity score-matched young psoriasis patients each in the biologic and oral systemic groups. Those who developed PsA within 1 year of therapy initiation were excluded.
Over more than 8 years of follow-up, PsA occurred in 5.9 percent of patients in the biologic group vs 20.6 percent of those in the oral systemic group. The cumulative incidence rate was 26.1 vs 78.6 per 1,000 person-years.
The finding has important implications, given that patients “diagnosed with psoriasis at an early age experience chronic inflammation, which can significantly impact quality of life,” said lead investigator Gabriela Palma from Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, US.
“Paediatric patients affected by chronic inflammatory skin conditions face years of IL-17/IL-23 upregulation and impactful sequelae,” Palma added.
Biologics have already been shown to mitigate the risk of PsA progression in adults, and the present real-world study provides evidence of the drugs’ effectiveness in younger populations, according to Palma. [Arthritis Rheumatol 2022;74:237-243]