P0851 Real-world analysis of risankizumab and upadacitinib treatment persistence according to disease location in patients with Crohn’s disease: Data from the CREdIT Registry

P1004 Efficacy and safety of risankizumab among patients in China with Ulcerative Colitis: A post hoc sub analysis of the randomized phase 2b/3 INSPIRE study

DOP085 Baseline predictors and clinical outcomes of risankizumab dose optimization: a real-world multicenter retrospective study

DOP055 Efficacy and Safety Up to 3 Years of Risankizumab Maintenance Treatment in Patients With Moderately to Severely Active Ulcerative Colitis: Interim Results from Phase 3 COMMAND Open-Label Extension Study

P0765 Serum risankizumab levels are associated with biochemical remission in Crohn’s disease

P0791 Real-World One-year Effectiveness of Risankizumab in Crohn’s Disease: Clinical, Biochemical and Ultrasound responses. A single-centre, observational, retrospective study.

P0283 Assessment of the ultrasound response to risankizumab at weeks 12 and 52 in patients with Crohn’s disease. A single centre, observational, retrospective study.

Introduction & Objectives: This analysis aimed to assess the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 244 of the KEEPsAKE 2 trial. Materials & Methods: KEEPsAKE 2 is an ongoing, multicenter, phase 3 clinical trial in patients with active PsA and previous intolerance or inadequate response to 1 or 2 biological therapies (Bio-IR) and/or ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Patients were randomized 1:1 to receive RZB 150 mg or placebo (PBO) for a 24-week double-blind period. By week 28, all patients were switched to open-label RZB and administered the study drug every 12 weeks thereafter. Safety and efficacy were assessed in all patients who received ≥ 1 dose of RZB. Statistical analyses included nonresponder imputation incorporating multiple imputation (NRI-MI) for binary endpoints and multiple mixed response model (MMRM) for continuous endpoints. Safety assessments based on treatment-emergent adverse events (TEAEs) are summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [E/100PYs]). Results: Patients on open-label RZB maintained similar efficacy results at week 244 as those reported previously at weeks 24, 52, 100, 148, and 196. At week 244, 49.6% of patients initially randomized to RZB and 42.9% of patients who switched from PBO to RZB (PBO/RZB) achieved ACR20; 30.4% on RZB and 28.3% on PBO/RZB achieved ACR50; 19.2% on RZB and 15.5% on PBO/RZB achieved ACR70; 29.9% on RZB and 27.4% on PBO/RZB achieved minimal disease activity (MDA). Among patients with baseline psoriasis severity affecting ≥ 3% body surface area, 61.8% on RZB and 52.1% on PBO/RZB achieved a 90% improvement in psoriasis area severity index (PASI90). Among patients with enthesitis or dactylitis at baseline, 45.6% on RZB and 42.4% on PBO/RZB achieved resolution of enthesitis (Leeds Enthesitis Index = 0), and 70.0% on RZB and 47.4% on PBO/RZB achieved resolution of dactylitis (Leeds Dactylitis Index = 0). For patients with a baseline HAQ-DI score ≥ 0.35, clinically meaningful improvements occurred in 33.2% on RZB and 32.1% on PBO/RZB. Week 244 safety assessments were consistent with those from the 24-week placebo-controlled study and through the open-label extension period: overall TEAEs (165.8 E/100PYs), serious TEAEs (9.7 E/100PYs), and any TEAE leading to discontinuation of RZB (1.5 E/100PYs). Conclusion: Long-term treatment with RZB demonstrates durable efficacy and a consistent safety profile through 244 weeks for adult patients with active PsA and inadequate response to biological therapies and/or csDMARD(s).

Background/Purpose: Risankizumab (RZB) is an approved, optimized inhibitor of IL-23 for treating adults with moderate-to-severe plaque psoriasis (PsO), psoriatic arthritis (PsA), Crohn’s disease and ulcerative colitis. VALUE is a post-marketing observational study (PMOS) assessing the durability of response of RZB in real world practice. In this post hoc analysis, we report the interim drug survival of RZB and other biologic therapies (OtherBios) in a subgroup of patients with PsO and concomitant PsA. Methods: VALUE (NCT03982394) is a multi-country, prospective PMOS. This post hoc analysis includes data from the subset of patients with PsO who were also diagnosed with concomitant PsA by a rheumatologist. Drug survival, defined as patients staying on the biologic they initiated at study enrollment, was assessed using the proportion of patients with treatment substance changes, and the cumulative probability of treatment changes. Treatment results were compared as RZB vs OtherBios at 25 months and RZB vs TNFα inhibitor (TNFi) vs IL-17i at 25 months. Results are reported from an interim database lock on 09 December 2024. All enrolled patients who received at least one dose of study medication were included in this treatment substance change analysis. Propensity score matching (PSM) with a 1:1 ratio using greedy algorithm and exact match for biologic-naive/biologic-experienced status was used to account for group imbalances. Nominal P values are reported. Results: This interim analysis included 255 (RZB) and 207 (OtherBios) patients diagnosed with PsO and concomitant PsA. Patients treated with RZB were older (53.5 years vs 49.3 years, P < 0.05) and had more severe skin disease as assessed by baseline psoriasis area and severity index (RZB vs OtherBios), (15.0 vs 13.1, P < 0.05), and body surface area (24.0% vs 19.1%, P < 0.05) than patients treated with OtherBios. Differences were balanced in the PSM set and results from PSM set are shown below. Patients receiving RZB were significantly less likely to require a treatment substance change than those receiving OtherBios (12.6% vs 30.3%, P <0.05) at month 25 of treatment. The probability of treatment substance change (95% CI) at month 25 based on the Kaplan-Meier curve for time to first treatment substance change was 0.11 (0.06, 0.17) for patients receiving RZB vs 0.31 (0.23, 0.41) for patients receiving OtherBios (P < 0.05). In assessing drug survival by mechanism of action (RZB as reference vs TNFi vs IL-17i) at 25 months, patients receiving RZB were less likely to require a treatment substance change (12.6% vs. 43.8% vs 26.4%, P <0.05). The probability of treatment substance change (95% CI) at month 25 based on the Kaplan-Meier curve for time to first treatment change was 0.11 (0.06, 0.19) in the RZB group, 0.44 (0.28, 0.63) in the TNFi group, and 0.28 (0.18, 0.44) in the IL-17i group (P < 0.05). Conclusion: Patients with PsO and concomitant PsA who were treated with RZB in real-world practice had higher drug survival and were less likely to require treatment changes compared to patients receiving OtherBios including TNFi and IL-17i.

Introduction Psoriasis (PsO) is a chronic immune-mediated disease that presents as thick and scaly skin plaques. Several biologics and oral treatments are available for the treatment of PsO, but variations across efficacy, safety, and treatment endpoints can make treatment optimization challenging for physicians in the absence of head-to-head comparisons. Risankizumab (RZB), an IL-23 inhibitor, and deucravacitinib (DEU), a tyrosine kinase 2 inhibitor, are both approved for the treatment of moderate-to-severe PsO. This study is evaluating the safety and efficacy of RZB vs DEU for the treatment of patients with moderate PsO without prior biologic treatment. Methods IMMpactful is a phase 4 (NCT06333860), global, multicenter, randomized, open-label, efficacy assessor-blinded, active comparator study examining the effect of RZB vs DEU in adult patients with moderate PsO. Patients (≥ 18 years) eligible for systemic treatment with no prior biologic exposure, with body surface area 10%-≤15%, psoriasis area and severity index (PASI) ≥ 12, and static physician global assessment (sPGA) of 3 (moderate) were enrolled. The 52-week treatment period was split into 2 periods. In period A (weeks 0–16), patients were randomized (1:2) to subcutaneous (SC) injection of RZB 150 mg on Day 1 and Week 4 or oral DEU 6 mg daily (QD), respectively. In period B (weeks 16–52), patients continued RZB every 12 weeks, and patients initially randomized to DEU were re-randomized 1:1 to RZB 150 mg SC or oral DEU 6 mg QD and stratified by PASI 90 response (nonresponder, responder). In period A, the coprimary endpoints were achievement of ≥ 90% improvement in PASI (PASI 90) and achievement of sPGA 0 or 1 (sPGA 0/1) with at least a 2-grade improvement from baseline. Ranked secondary endpoints for period A included the achievement of PASI 100, and sPGA 0 with at least a 2-grade improvement from baseline at Week 16. Results from period A are presented. Nonresponder imputation incorporating multiple imputations was used to handle missing data. Results Of the 393 enrolled patients, 131 (mean age [SD]: 47.3 [14.1] years) were randomized to RZB, and 262 (mean age [SD]: 44.8 [13.8] years) were randomized to DEU. Baseline disease characteristics were similar. A significantly higher proportion of patients treated with RZB achieved PASI 90 (57.3% vs 22.9%, P < .0001), sPGA 0/1 (80.2% vs 39.7%, P < .0001), PASI 100 (27.5% vs 6.5%, P < .0001), and sPGA 0 (27.5% vs. 6.9%, P < .0001) compared with patients treated with DEU. The proportion of patients with treatment-emergent adverse events was 33.6% (RZB) and 42.9% (DEU). The proportion of patients with adverse events related to study drug was 6.1% (RZB) and 15.3% (DEU). One serious adverse event of joint injury was reported by a patient receiving RZB, deemed unrelated to the study drug. There were no deaths reported. Conclusion Treatment with RZB provided greater clinical response compared with DEU in adults with moderate PsO, and safety results were consistent with the known safety profile of RZB and DEU. These results support the opportunity to elevate treatment outcomes in biologic naïve patients with moderate PsO.

Introduction & Objectives: Risankizumab (RZB) is a humanized immunoglobulin G1 monoclonal antibody that inhibits interleukin-23 (IL-23) by targeting its p19 subunit. This post hoc analysis evaluated the maintenance of clinical responses after approximately 5 years of RZB treatment in patients enrolled in the ongoing phase 3 KEEPsAKE 1 and KEEPsAKE 2 clinical trials. Materials & Methods: Eligibility for enrollment required patients to have active PsA and inadequate response or intolerance to ≥ 1 conventional synthetic disease modifying antirheumatic drug (csDMARD) for KEEPsAKE 1 (NCT03675308), or inadequate response or intolerance to 1 or 2 biologic DMARDs and/or ≥ 1 csDMARD for KEEPsAKE 2 (NCT03671148). In both studies, patients were initially randomized 1:1 to receive RZB 150 mg or placebo for a 24-week double-blind period and received open-label RZB thereafter. Maintenance of response analyses were based on patients who were responders at week 24 for each endpoint. Assessments included improvement of ≥ 20%/50%/70% in PsA symptoms using the American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥ 90% in Psoriasis Area and Severity Index (PASI90; in patients with ≥ 3% body surface area affected by psoriasis at baseline), clinically meaningful reduction in pain≥ 10 mm on a visual analog scale [VAS] in patients with > 10 mm at baseline), chievement of the MDA patient pain criteria (VAS ≤ 15 mm in patients with VAS > 15 mm at baseline), and clinically meaningful reduction in modified Bath Ankylosing Spondylitis Disease Activity Index (mBASDAI; ≥ 1.1 point-decrease in patients with a score > 1.1 at baseline). Nonresponder imputation incorporating multiple imputation (NRI-MI) was used with data missing due to COVID-19 or geopolitical conflict; all other missing data were imputed as nonresponders. Safety assessments of the overall population have been performed in previous studies. Results: The majority of patients who received RZB during the double-blind period and achieved ACR20 at week 24 maintained ACR20 at week 244 (KEEPsAKE 1: 66.7%; KEEPsAKE 2: 64.0%). Achievement of ACR50 (KEEPsAKE 1: 55.0%; KEEPsAKE 2: 56.1%) and ACR70 (KEEPsAKE 1: 52.2%; KEEPsAKE 2: 61.5%) was similarly maintained at week 244 for patients randomized to continuous RZB. Most week 24 responders maintained achievement of MDA (KEEPsAKE 1: 63.6%; KEEPsAKE 2: 64.9%) and PASI90 (KEEPsAKE 1: 71.5%; KEEPsAKE 2: 72.5%) at week 244. Clinically meaningful reductions in pain (KEEPsAKE 1: 66.1%; KEEPsAKE 2: 58.4%) and achievement of the MDA patient pain criteria (KEEPsAKE 1: 60.4%; KEEPsAKE 2: 48.8%) were maintained at week 244. Most patients maintained clinically meaningful reductions in mBASDAI score from week 24 to week 244 (pooled KEEPsAKE 1 and KEEPsAKE 2: 62.5%). Conclusion: RZB demonstrated durable long-term efficacy across multiple clinical endpoints among patients with active PsA. Among RZB-treated patients who achieved treatment response targets at week 24, those responses were maintained at week 244.

Introduction & Objectives Numerous biological therapies have become available in recent years for treating moderate-to-severe psoriasis (PsO). Studies providing real-world data directly comparing the effectiveness of these biologics are relatively scarce or limited by short observation periods. The Psoriasis Study of Health Outcomes (PSoHO) is a 36-month, non-interventional, international cohort study of patients (pts) with moderate-to-severe PsO, which enrolled 1981 pts ≥ 18 years of age from 23 countries, providing long-term data from a real-world setting needed for evidence-based care. Materials & Methods The outcomes presented are the most contemporaneous prespecified endpoints: PASI100/90 durability, defined as individual pts achieving PASI100/90 at Week 12, and maintaining PASI100/90 at months 6, 12, 18, and 24. Adjusted odds ratios with 95% confidence intervals were generated using marginal structural models (MSM), which accounted for key confounders as well as treatment switching and discontinuation. Odds ratios are presented with non-responder imputation (NRI) and as observed (non-imputed) for ixekizumab (IXE) versus secukinumab (SEC), tildrakizumab (TILD), guselkumab (GUS), risankizumab (RIS), adalimumab (ADA), and ustekinumab (UST) for the overall population and a European Medicines Agency (EMA) on-label sub-population. Results The adjusted analysis showed greater odds of durability response for IXE versus SEC, TILD, GUS, ADA, and UST, and similar odds to RIS for both the PASI90 and PASI100 durability outcomes in the overall population. The results of the EMA on-label sub-population analysis were similar, with the exception of the PASI100 durability outcome, where pts treated with IXE had significantly greater odds than those treated with RIS and were similar to those treated with SEC. Conclusion: Durability in the PSoHO study is based on rapid skin clearance and sustained therapeutic response, the primary treatment goals of many patients with PsO. It has previously been demonstrated that patients who achieve PASI100 earlier experience more days under a DLQI score of 0 or 1, emphasizing the correlation between the time taken to achieve total skin clearance and patients' quality of life. A limitation of long-term observational studies is potential bias caused by treatment switching, which can be impacted by study length, higher skin involvement, treatment costs, and access, but also by comorbid PsA, which approximately one-third of pts with PsO also suffer from. The MSM analysis was used to control for this bias. PSoHO provides real-world evidence that ixekizumab-treated pts show better PASI100/90 durability outcomes than those treated with adalimumab, ustekinumab, secukinumab, guselkumab, and tildrakizumab, while being similar to risankizumab in the overall population.

Background:Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), affects approximately 4.9 million individuals globally. Advanced therapies have significantly improved IBD management; however, maintenance doses commonly exceed labeled recommendations for optimal efficacy. This study aimed to estimate the financial impact of introducing Risankizumab (RISA) for CD and Upadacitinib (UPA) for UC treatment in Saudi Arabia (KSA), incorporating adjusted dosing practices rather than label doses alone.Methods:Cost-calculation model (CCM) was developed to estimate average monthly costs per patient, capturing complexities like induction, maintenance adjustments, discontinuation, switching, re-induction, and death. Data on adjusted dosing were collected via two expert interviews. The CCM compared scenarios “with” and “without” UPA for UC, and “with” and “without” RISA for CD, analyzing financial impacts over a 5-year horizon, from the payer’s perspective.Results:Adjusted UC treatment doses increased five-year costs by 22% compared to label doses. Introducing UPA with adjusted dosing resulted in a 6.7% higher cost versus scenarios without UPA, based on tender prices. For CD, adjusted dosing increased treatment costs by 24.5% compared to label doses. However, adding RISA with adjusted dosing slightly reduced the total drug cost by 0.35%.Conclusion:Expert interviews and detailed patient pathway modeling indicated substantial cost increases for UC and CD treatments in KSA when adjusted doses were considered. The introduction of UPA and RISA under adjusted dosing yielded minor financial differences, with potential implications for economic evaluations in other regions.

IntroductionThis study assessed the real-world effectiveness of risankizumab (RZB) and treatment satisfaction in biologic-naïve patients with psoriatic arthritis (PsA) across the USA and Europe.MethodsData were drawn from the Adelphi Real World Spondyloarthritis Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with PsA receiving RZB 150 mg subcutaneous injections in Europe (France, Germany, Italy, Spain, UK) and the US, conducted from June 2023–June 2024. Physicians reported changes in body surface area (BSA), dactylitis, enthesitis, TJC68, and SJC66 and assessments of pain and fatigue on a 0–10 scale (higher scores indicating worse outcomes) from initiation to data collection, evaluated using McNemar or t-tests (p < 0.05 considered significant). Clinically meaningful improvements were complete resolution of dactylitis, enthesitis, TJC68, and SJC66 and pain (≥ 1.0-unit) and fatigue (≥ 3.0-unit) reductions. Physician and patient satisfaction with disease control was also reported. Outcomes were analyzed for the full cohort and stratified by prescription of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) prior to the survey or at data collection vs csDMARD-naïve.ResultsOverall, 127 physicians reported on 192 patients with PsA (Europe 64%, US 36%). Mean ± SD patient age was 44.2 ± 10.7 years, and 45% were female. From RZB treatment initiation to time of data collection, resolution of dactylitis (82%) and enthesitis (90%), and improvements to TJC68 (− 3.7 ± 6.3), SJC66 (− 2.5 ± 5.1), pain (− 3.9 ± 2.4), fatigue (− 2.7 ± 2.6), and BSA (− 10 ± 10%) were observed (p < 0.001 for each) for the full cohort, with significant changes observed in both csDMARD subgroups. Patient and physician satisfaction with disease control was 95% and 98%, respectively.ConclusionBiologic-naïve patients with PsA starting RZB demonstrated significant and meaningful improvements in joint symptoms, pain, and fatigue in real-world settings. High levels of satisfaction with RZB for disease control were reported by both patients and physicians.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-025-00801-6.

Abstract Background Risankizumab (RSK) (Skyrizi®), a humanized monoclonal antibody against the p19 subunit of interleukin 23 (IL23), is used to treat Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (PsO), and psoriatic arthritis (PsA). By blocking IL23 binding to its receptor, RSK inhibits IL23-dependent cell signaling and release of proinflammatory cytokines. Therapeutic drug monitoring of biologic drugs and their antibodies can expedite clinical decision-making, improve efficacy, and may lead to reduced cost. Here, analytic performance characteristics of a new lab developed electrochemiluminescence immunoassays for RSK and anti-RSK antibody concentrations are presented. Methods We developed and validated electrochemiluminescence immunoassays for RSK and its anti-drug antibody (ADA) in accordance with FDA guidance for therapeutic protein immunogenicity testing and bioanalytical method validation. The drug assay utilizes antibodies against RSK and is designed to detect free (ADA-unbound) pharmacodynamically active RSK. The ADA assay measures total binding antibodies (including IgM and IgG) against RSK. Analytical performance including accuracy, precision, lower limit of quantitation (LLOQ), upper limit of quantitation (ULOQ), dilutional linearity, specificity, and drug tolerance (for the ADA assay) was assessed. Results The RSK dug assay has an analytical measurement range (AMR) of 0.75 – 60 µg/mL with an 80-fold maximum dilution (maximum quantifiable value of 4,800 µg/mL). Lower limit of quantitation (LLOQ) is 0.75 ug/mL where steady state RSK drug trough concentrations are reported to be around 4 - 9 µg/mL in UC and CD depending upon the dose. Within the AMR, bias for the assay is = ±7.5% and imprecision is = 9.8% CV. There is no cross-reactivity with other biologics used to treat similar diseases or with other anti-IL23 inhibitor drugs. The ADA AMR is 25 – 5,000 ng/mL with a maximum allowable dilution of 100-fold (maximum reportable concentration of 500,000 ng/mL). Assay LLOQ is 25 ng/mL. Assay bias is = 14.0% and imprecision is = 14.5% CV for samples within the AMR. Drug tolerance was confirmed by sample recovery of 80 – 120 % for samples with drug levels as high as 120 µg/mL and no cross-reactivity was detected for ADAs to other biologics. All positive ADA samples undergo a confirmatory test step where signal suppression upon the addition of high concentrations of RSK confirms the RSK-specificity of the anti-drug antibodies. Conclusion This study demonstrates the robust analytic performance of two new TDM assays to quantify RSK drug and anti-RSK antibodies. Accurate quantitation of RSK drug enables dose optimization at post-induction and maintenance time points, while this drug-specific, drug tolerant, and high resolution anti-RSK assay allows for accurate immunogenic assessment at signs of lack or loss of response. Together, these TDM assays aim to optimize the use and longevity of RSK through precise drug and immunogenicity monitoring.

Background:Crohn’s disease (CD) remains a challenging condition, especially in patients with moderate-to-severe disease. Risankizumab (RZB), an anti-IL-23p19 monoclonal antibody, has shown efficacy in clinical trials. However, real-world data (RWD) in Asian populations are limited.Objectives:To assess the effectiveness and safety of Risankizumab in Asian patients with CD.Design:Multicenter cohort study.Methods:This study enrolled adult patients with moderate-to-severe CD who received Risankizumab between September 2024 and May 2025 in Taiwan. Efficacy was assessed at weeks 4, 8, and 12 using CD Activity Index (CDAI), patient-reported outcomes-2 (PRO2), and inflammatory bowel disease (IBD)-disk scores. Safety outcomes and treatment response by prior biologic exposure, including Ustekinumab (UST), were evaluated.Results:Forty-nine patients (mean age 41.5 years, 69.4% male) were included. Clinical response rates were 53.1%, 75.5%, and 91.8% at weeks 4, 8, and 12, respectively; clinical remission was achieved in 12.2%, 22.4%, and 42.9%. PRO2 remission reached 53.5% by week 12. Both CDAI and IBD-Disk scores improved at weeks 4, 8, and 12 with statistical significance (p < 0.0001). Transmural healing was observed in 16.3% of patients at week 12. Clinical remission at week 12 was consistent regardless of prior Ustekinumab exposure (exposed 36.36% vs naïve 44.74%, p = 0.630) or biologic-naïve status (exposed 36.84% vs naïve 63.63%, p = 0.119). No severe adverse events were reported, but mild events included headache and transient liver enzyme elevation (each 2.04%).Conclusion:Risankizumab may demonstrate significant short-term efficacy and favorable safety in real-world treatment of moderate-to-severe CD in an Asian cohort. Long-term data are needed to confirm sustained outcomes and guide their optimal use across diverse CD populations.

The Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study investigating the comparative effectiveness and durability of biologic treatments for patients with moderate-to-severe psoriasis (PsO) over 36months. Patients were grouped into cohorts based on biologic class: anti-interleukin (IL)-17A/receptor A (anti-IL-17A), anti-IL-12/23, anti-IL-23 and anti-tumor necrosis factor (TNF)-α for the purpose of comparison. Additionally, the durability and effectiveness of individual biologic treatments were compared to ixekizumab (IXE). Effectiveness was assessed using Psoriasis Area and Severity Index (PASI) 90 and PASI100 response rates and durability, defined as achieving therapeutic response (PASI90/100) at week 12 and its maintenance at months 6, 12, 18 and 24. Statistical analysis included unadjusted descriptive summaries and model-based comparisons that accounted for baseline confounders using the frequentist model averaging (FMA) framework and marginal structural models (MSM) that accounted for both baseline and time-varying confounders. Results demonstrated that patients treated with anti-IL-17A biologics had significantly higher odds of achieving PASI100 and PASI90 compared to those treated with anti-IL-12/23 and anti-TNFα biologics. Specifically, at 24months, IXE showed greater PASI100 and PASI90 response rates compared to adalimumab (ADA) and ustekinumab (UST), with adjusted odds ratios of 1.9 and 2.3 for PASI100 and 2.0 and 2.5 for PASI90, respectively. IXE-treated patients also exhibited higher durability rates for PASI100 and PASI90 compared to ADA, UST, secukinumab (SEC), tildrakizumab (TILD) and guselkumab (GUS), with adjusted odds ratios (non-responder imputation [NRI]) between 1.7 and 4.3 (PASI100) and 1.6 and 4.2 (PASI90), while being similar to risankizumab (RIS). This study provides valuable real-world data on the long-term effectiveness and durability of biologic treatments for PsO, emphasizing the advantages of anti-IL-17A biologics, particularly IXE, in achieving and maintaining therapeutic responses. These findings support dermatologists in making informed decisions regarding PsO treatment strategies. The study was registered at the European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCEPP24207).

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients.

Biologic dosing frequency is a key concern among psoriasis (PsO) patients and physicians, yet dosing optimization remains a challenge. This study evaluates patient dosing preferences for IL-17 and IL-23 inhibitors, risankizumab (RZB) every 12 weeks, guselkumab (GUS) every 8 weeks, and ixekizumab (IXE) every 4 weeks, in managing PsO. This phone survey study evaluated 87 adults on RZB (n = 29), GUS (n = 35), or IXE (n = 23) from 2019 onward at two clinical sites. Patients were assessed for baseline PsO bothersome severity, current dosing frequency satisfaction, frequency of PsO flares, and preferred dosing frequency. Most patients were males (57.5%) with an average age of 54.1 years and an average treatment duration of 19.0 months. At baseline before treatment, 87% were ‘very bothered’ by their PsO. After treatment, 86% were either ‘3-somewhat’ or ‘4-very satisfied’ with their current dosing schedule, with no significant differences between each drug ( P = 0.7). Across all biologics the majority of participants (62% with RZB, 57% with GUS, and 48% with IXE) preferred maintaining their current dosing frequency. No statistically significant differences were observed in dosing frequency preference between treatment groups, suggesting dosing schedule is not a primary concern for most patients. This aligns with previous research demonstrating effective disease control is the most important factor for patient satisfaction; however, tailoring dosing regimens to individual patient needs can also strengthen long-term adherence, as demonstrated in recent studies.

A multicenter study of the real-world effectiveness and safety of risankizumab in Crohn's disease.