PSoHo cohort study – an interim assessment

In clinical trial programs, certain subgroups of patients are excluded based on the respective inclusion criteria. Register studies provide additional data from everyday practice. To date, there have been few direct real-world comparisons of the efficacy of different biologics in patients with moderate to severe psoriasis. The international cohort study Psoriasis Study of Health Outcomes (PSoHO) was designed against this background. This is an ongoing study, with evaluations of partial samples currently available.

Although randomized controlled clinical trials (RCTs) are considered the gold standard for assessing the efficacy and safety of potential therapies, real-world data is also needed to reflect the heterogeneous patient population in everyday practice [2]. The PSoHo cohort study included patients from 23 countries who had been diagnosed with moderate to severe psoriasis at least 6 months before baseline and who either started biologic therapy or switched to another biologic agent as part of routine clinical care [5]. Patients were grouped into a cohort that received anti-IL-17A antibodies (ixekizumab, secukinumab) and a cohort that was treated with other biologics (brodalumab, adalimumab, certolizumab pegol, etanercept, infliximab, ustekinumab, guselkumab, risankizumab and tildrakizumab).

Subgroup-specific efficacy comparisons at week 12

In a publication published in the journal Advances in Therapy 2023 , analyses of a subsample of the PSoHo data set are reported. In total, data from 1981 psoriasis patients included in the PSoHo cohort were analyzed (Table 1) [2].

The patient data were grouped into seven clinically relevant demographic and disease-related characteristics according to a priori defined criteria [2]:

• Gender (male, female)
• Age (
• Body mass index (≤30 or >30 ^kg/m2)
• Ethnicity (white skin color or Asian origin)
• Psoriasis disease duration (<15 or ≥15 years)
• Comorbid psoriatic arthritis
• Previous biologics therapies

Across these subgroups, efficacy was compared between the anti-IL-17A cohort (ixekizumab, secukinumab) versus ustekinumab, adalimumab, guselkumab, risankizumab. Treatment groups or biologics cohorts with fewer than 100 patients were not included [2]. In addition to the proportion of patients who achieved Psoriasis Area and Severity Index (PASI) 90 and/or static Physician Global Assessment (sPGA) 0/1, the subgroup-specific PASI100 and PASI90 response rates at week 12 were calculated.

PsA subgroup: comparatively high response rates to anti-IL-17-Ak

As shown in Table 2 , patients in the anti-IL-17A cohort were significantly more likely to reach the primary endpoint (sPGA 0/1 and/or PASI90) at week 12 compared to the other biologics cohorts [2]. This also applies to the other subgroups, with the exception of the ethnicity category. With regard to the subgroup of patients with comorbid psoriatic arthritis (PsA), the anti-IL-17A-Ak showed a 4-fold and 3-fold increased probability for PASI100 and PASI90, respectively. This indicates that psoriasis patients with joint involvement particularly benefit from treatment with IL-17A inhibitors. With regard to the other subgroups, any differences across all clinical outcome parameters were far less striking. For example, there were no significant gender-related differences in efficacy, which is consistent with a Spanish registry study [6]. Various biologics also showed similar efficacy between the age groups of <65- and ≥65-year-olds in the present subgroup analysis, although the proportion of patients aged ≥65 was relatively low [2]. The study situation is heterogeneous regarding the extent to which age influences the treatment effects of biologic therapy for psoriasis [7,8].

The question of how a BMI >30 ^kg/m2 influences the efficacy of biologics is also controversially discussed in the specialist literature. In the present PSoHo subsample, treatment with secukinumab or ixekizumab proved to be similarly effective to risankizumab in obese patients. The findings are also inconsistent regarding the extent to which a longer duration of illness influences clinical outcomes [7,9,10]. In the previous subsample, it had no major influence on the response rates whether the duration of the disease was less or more than 15 years. Patients with a longer duration of disease have often already undergone several biologic therapies and other systemic treatments [3]. The treatment of biologics-experienced patients remains a challenge [2]. It has been shown that the treatment discontinuation rate tends to be higher than in biologics-naïve patients [2,4,10].

Literature:

1. Masson RM, et al: Users of biologics in clinical practice: would they be eligible for phase III clinical studies? Cohort Study in the French Psoriasis Registry PSOBIOTEQ. JEADV 2020; 34: 293-300.
2. Lynde C, et al: Comparative Effectiveness of Biologics Across Subgroups of Patients with Moderate-to-Severe Plaque Psoriasis: Results at Week 12 from the PSoHO Study in a Real-World Setting. Adv Ther 2023; 40(3): 869-886.
3. Papp KA, et al: Impact of previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE-2 and AMAGINE-3. BJD 2018; 179: 320-328.
4. Ger T-Y, et al: Effectiveness and safety of secukinumab for psoriasis in real-world practice: analysis of subgroups stratified by prior biologic failure or reimbursement. Therap Adv Chronic Dis 2019; 10:2040622319843756.
5. Pinter A, et al: Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an International observational psoriasis study of health outcomes (PSoHO). JEADV 2022; 36: 2087-2100.
6. Hernández-Fernández CP, et al: Effect of sex in systemic psoriasis therapy: differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort. Acta Derm Venereol 2021;101:adv00354.
7. Crowley JJ, et al: Efficacy of risankizumab versus secukinumab in patients with moderate-to-severe psoriasis: subgroup analysis from the IMMerge study. Dermatol Ther 2022; 12: 561-575.
8. Blauvelt A, et al: Efficacy of guselkumab versus secukinumab in subpopulations of pa-tients with moderate-to-severe plaque psoriasis: results from the ECLIPSE study. J Dermatol Treat 2021;33(4): 2317-2324.
9. Papp KA, et al: Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 2) Lancet 2008; 371: 1675-1684.
10. Torres T, et al: Drug survival of IL-12/23, IL-17 and IL-23 inhibitors for psoriasis treatment: a retrospective multi-country, multicentric cohort study. Am J Clin Dermatol 2021; 22: 567-579.

DERMATOLOGY PRACTICE 2023; 33(5): 46-47