Combination Targeted Therapy Shows Comparable Infection Risk to Standard Treatment in PsA

Adult patients with psoriatic arthritis (PsA) treated with combination targeted therapy (CTT) have a risk of infection similar to those receiving standard treatment, according to findings published in JAMA Dermatology.¹

Although a variety of therapies with different mechanisms are available for PsA, up to half of patients fail to achieve remission with initial or subsequent monotherapy. This has led to interest in combining 2 or more agents with different mechanisms of action to treat PsA.

Evidence from other diseases regarding this method has been mixed. In rheumatoid arthritis, CTT provided little additional efficacy but was linked to higher rates of serious infections. In contrast, recent studies in inflammatory bowel disease demonstrated more promising outcomes with comparable safety profiles.²

However, for PsA, data on real-world CTT use and safety are limited.¹ To address this gap, the investigators analyzed relevant data from the IBM MarketScan Commercial Claims Database, spanning 2015 to 2024, characterizing the prevalence of CTT and the risk of infections in patients with PsA treated with this method.

The researchers identified adults with PsA by using a validated claims algorithm. They then divided them into 2 groups: patients receiving standard therapy and those receiving CTT. Patients in the standard therapy cohort were matched 2:1 with those in the CTT cohort.

The study included 82,399 eligible individuals. Of these, 53,025 (64.4%) had at least 3 consecutive months of medication fill data for any PsA medication, and 542 (1.0%) received 2 or more targeted therapy classes. The 6-month cohorts included 39,101 patients on standard therapy and 200 patients on CTT. The most common CTT regimens combined a tumor necrosis factor (TNF)–α inhibitor and apremilast (34.8%-37.3%) or an IL-17 inhibitor and apremilast (27.1%-28.8%).

Rates of serious infection among patients receiving 3, 4, and 6 months of CTT were 7.38, 7.92, and 15.00 per 1000 patients, respectively. After adjusting for age, sex, therapy duration, and Charlson Comorbidity Index (CCI) score, no significant differences were found compared with standard therapy at 3 (adjusted relative risk [aRR], 0.44; 95% CI, 0.17-1.17), 4 (aRR, 0.51; 95% CI, 0.17-1.58), or 6 (aRR, 1.02; 95% CI, 0.33-3.11) months.

Propensity score (PS) matching yielded similar results, with no significant differences in serious infection risk at 3 (RR, 0.53; 95% CI, 0.17-1.63), 4 (RR, 0.75; 95% CI, 0.20-2.81), or 6 (RR, 1.50; 95% CI, 0.34-6.65) months.

Opportunistic infection risk was also comparable between groups. At 3, 4, and 6 months of CTT, incidence rates were 1.85, 0, and 0 per 1000 patients. After adjustments, there were no significant differences at 3 (aRR, 1.02; 95% CI, 0.14-7.29), 4 (aRR, not applicable), or 6 (aRR, not applicable) months in individuals receiving CTT vs standard therapy treatment. Additionally, PS matching showed no differences in opportunistic infection risk at 3 (RR, 1.00; 95% CI, 0.09-11.02), 4 (RR, not applicable), or 6 (RR, not applicable) months.

The researchers acknowledged several limitations. Although the sample size was larger than that of similar studies, they highlighted the small sizes of the CTT cohorts. Additionally, most CTT regimens included apremilast, which may limit the generalizability of their findings to other drug combinations. Nonetheless, they expressed confidence in their results and underscored the need for further research.

“This study found no significant difference between the incidence of serious bacterial and opportunistic infections requiring hospitalization compared with standard therapy, suggesting that combination targeted therapy may not be associated with significantly increased infection risk, but further larger studies are needed,” the authors wrote.

References

1. Wu A, Zhang A, Guo Y, et al. Comparative risk of infection and prevalence of combination targeted therapy in psoriatic arthritis. JAMA Dermatol. Published online August 20, 2025. doi:10.1001/jamadermatol.2025.2980
2. Feagan BG, Sands BE, Sandborn WJ, et al. Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial. Lancet Gastroenterol Hepatol. 2023;8(4):307-320. doi:10.1016/S2468-1253(22)00427-7