Real-world evidence for Ustekinumab in psoriasis: observational cohorts, registries, propensity matching, and outcomes.
Overview: what real-world evidence adds for ustekinumab
Ustekinumab, an IL-12/23p40 inhibitor, has substantial real-world evidence in moderate-to-severe psoriasis from large national registries, multinational observational cohorts, and claims-based comparative safety/effectiveness studies. Across these datasets, ustekinumab generally shows strong treatment persistence and a favorable safety profile, particularly compared with adalimumab and several older biologics. However, newer IL-23p19 inhibitors and some IL-17/IL-17A agents often show greater skin-clearance effectiveness or longer effectiveness-related drug survival, especially in biologic-experienced populations.
1. Drug survival and persistence in psoriasis registries
BADBIR: ustekinumab as a strong long-term comparator
The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) provides some of the largest real-world data. In a prospective cohort of 16,122 biologic treatment courses—adalimumab 6,607, ustekinumab 5,405, secukinumab 2,677, guselkumab 730, and ixekizumab 703—ustekinumab had high 1-year crude drug survival for effectiveness: 0.89 (95% CI, 0.88–0.89), compared with adalimumab 0.81 (95% CI, 0.80–0.82), secukinumab 0.86 (95% CI, 0.85–0.87), ixekizumab 0.86 (95% CI, 0.83–0.89), and guselkumab 0.94 (95% CI, 0.92–0.96). In adjusted models, adalimumab had poorer effectiveness-related survival than ustekinumab, with an adjusted hazard ratio of 2.37 (95% CI, 2.03–2.76), whereas guselkumab had better survival than ustekinumab, adjusted HR 0.13 (95% CI, 0.03–0.56) (Yiu et al., 2022).
For safety-related persistence in the same BADBIR analysis, ustekinumab also performed well: 1-year crude safety survival was 0.94 (95% CI, 0.94–0.95), similar to secukinumab 0.94 and close to guselkumab 0.96. Adalimumab and ixekizumab had lower adjusted safety survival versus ustekinumab, with adjusted HRs of 1.66 (95% CI, 1.46–1.89) and 1.52 (95% CI, 1.13–2.03), respectively (Yiu et al., 2022).
Newer BADBIR analysis: IL-23p19 agents surpass ustekinumab for effectiveness survival
A later BADBIR cohort including 19,034 treatment courses—adalimumab 6,815, ustekinumab 5,639, secukinumab 3,051, ixekizumab 1,072, brodalumab 367, guselkumab 1,258, and risankizumab 832—found the highest adjusted 2-year survival times for effectiveness with guselkumab and risankizumab, both 1.93 years. Ustekinumab remained strong for safety, with adjusted safety survival 1.92 years (IQR 1.91–1.93), similar to guselkumab 1.92 and slightly below risankizumab 1.94 (Motedayen Aval et al., 2024). This positions ustekinumab as a durable and safe reference biologic, but no longer the top performer for effectiveness persistence in the IL-23 era.
DERMBIO: ustekinumab excels in biologic-naïve patients
The Danish DERMBIO registry analyzed 4,438 unique patients with psoriasis; 61.2% were male, mean age was 45.0 years, and 23.4% had psoriatic arthritis. Among biologic-naïve treatment series, ustekinumab showed superior 5-year persistence: standardized discontinuation risk was 0.37 (95% CI, 0.33–0.41), significantly lower than adalimumab 0.51 (95% CI, 0.49–0.54) and secukinumab 0.54 (95% CI, 0.48–0.60). Among biologic-experienced patients, however, ustekinumab’s 2-year discontinuation risk was 0.39 (95% CI, 0.36–0.43), while bimekizumab 0.27, guselkumab 0.29, and risankizumab 0.25 had significantly lower discontinuation risks (Schwarz et al., 2027).
2. Comparative effectiveness: PASI outcomes and durability
The international prospective non-interventional PSoHO study followed patients with moderate-to-severe psoriasis over 36 months and compared biologic classes using PASI90, PASI100, and durability. Analyses adjusted for baseline confounders using frequentist model averaging and for time-varying confounding using marginal structural models. At 24 months, ixekizumab showed higher response rates than ustekinumab: adjusted odds ratios were 2.3 for PASI100 and 2.5 for PASI90 versus ustekinumab. Ixekizumab also showed higher durability of PASI100 and PASI90 compared with ustekinumab, with adjusted odds ratios across comparators ranging from 1.7–4.3 for PASI100 and 1.6–4.2 for PASI90, while appearing similar to risankizumab (Pinter et al., 2025).
These findings align with randomized-trial network meta-analyses showing that newer biologics generally achieve higher short-term skin clearance than ustekinumab. For example, one network meta-analysis ranked ustekinumab below IL-17 inhibitors for PASI75 likelihood, with relative risk versus placebo 14.0 for ustekinumab compared with 15.4 for secukinumab, 17.3 for brodalumab, and 17.9 for ixekizumab (Loos et al., 2017). Although these are trial-derived, they contextualize why real-world clearance and durability may favor newer IL-17/IL-23 agents.
3. Safety: serious infections and adverse events
Propensity-weighted serious infection study
A large multi-database cohort compared hospitalization for serious infection among 123,383 patients with psoriasis or psoriatic arthritis initiating biologics or apremilast. During 117,744 person-years, there were 1,514 serious infections, crude incidence 1.29 per 100 person-years. Propensity score fine stratification and weighting were used for confounding control. Ustekinumab initiators had relatively low serious infection rates, 0.59–0.95 per 100 person-years across databases. Compared with ustekinumab, serious infection risk was higher for adalimumab, HR 1.66 (95% CI, 1.34–2.06); etanercept, HR 1.39 (95% CI, 1.01–1.90); infliximab, HR 2.92 (95% CI, 1.80–4.72); ixekizumab, HR 2.98 (95% CI, 1.20–7.41); and secukinumab, HR 1.84 (95% CI, 1.24–2.72). Certolizumab was not significantly different, HR 1.09 (95% CI, 0.68–1.75) (Jin et al., 2021).
BIOBADADERM: lower overall adverse event rates than adalimumab
The Spanish BIOBADADERM prospective registry included 4,212 patients, 7,590 treatment cycles, and 17,284 patient-years. Using propensity scores to reduce selection bias and adalimumab as the reference, ustekinumab had a significantly lower risk of all adverse events, adjusted incidence rate ratio 0.73 (95% CI, 0.65–0.82; p ≤ 0.002), compared with adalimumab’s all-adverse-event incidence of 614 per 1,000 patient-years (Olivares-Guerrero et al., 2024).
4. Effect modifiers: psoriatic arthritis, comorbidity, obesity, and biomarkers
A BADBIR retrospective observational study of 9,057 patients receiving ustekinumab or conventional systemic therapies found that patients with concomitant psoriatic arthritis had greater comorbidity burden, including hypertension, diabetes, obesity, depression, and work disability. Psoriatic arthritis was associated with shorter ustekinumab persistence, HR 1.98; depression also shortened persistence, HR 1.21, while male sex was associated with longer persistence, HR for male sex 0.72. Quality of life was negatively affected by both depression and PsA (Tillett et al., 2022).
The Western Japan Psoriasis Registry, including 1,003 patients, similarly found poorer drug survival across systemic interventions in biologic-experienced, obese, and PsA subgroups, with no major safety signals (Yanase et al., 2022).
Biomarker data from BADBIR/BSTOP suggest HLA-C06:02 positivity may predict better ustekinumab persistence. Among 3,094 patients with HLA data, HLA-C06:02-positive patients were less likely to discontinue ustekinumab for ineffectiveness, adjusted HR 0.56 (95% CI, 0.42–0.75) (Alabas et al., 2023).
Conclusion
Real-world evidence supports ustekinumab as a durable, well-tolerated biologic with favorable safety, especially regarding serious infections and adverse-event discontinuation. In biologic-naïve patients, registry data show excellent persistence versus adalimumab and secukinumab. However, newer IL-23p19 inhibitors—guselkumab and risankizumab—and some IL-17 agents often outperform ustekinumab for PASI90/PASI100 achievement or effectiveness-related drug survival. Patient factors matter: psoriatic arthritis, obesity, depression, prior biologic exposure, and HLA-C*06:02 status can modify outcomes. Thus, ustekinumab remains a strong real-world option, particularly when long-term tolerability and infection risk are central, but may be less competitive when maximal skin clearance is the primary goal.