ABSTRACT Background The Psoriasis Area and Severity Index (PASI), a composite measure of plaque psoriasis disease severity, is commonly used to determine treatment eligibility and response, but is time consuming for every‐day clinical use. The Gulliver‐Gestalt‐Psoriasis Area Severity Estimate (G2‐PASE) was developed to approximate PASI scores using Physician Global Assessment (PGA) and body surface area (BSA) measures. Objectives To determine the reliability and validity of G2‐PASE compared to PASI using data from a multi‐center, Canadian cohort of patients with plaque psoriasis. Methods Canadian patients with a history of moderate to severe plaque psoriasis enrolled in the first cohort of the Psoriasis Longitudinal Assessment and Registry (PSOLAR 1; a global, prospective, longitudinal, disease‐based registry) were included. The G2‐PASE for each patient was calculated by applying baseline PGA and BSA values available from PSOLAR patient data at enrollment. The correlation and reliability of G2‐PASE compared to PASI for each patient at enrollment was then assessed. A similar analysis was conducted to test the reproducibility of results previously published by a participating PSOLAR clinical trial site. Results Of the 1896 Canadian patients in PSOLAR 1, 1803 had PASI data and were included in this analysis. The average baseline PASI score was 5.52 (SD 6.44, range 0.00–64.30), and the mean calculated G2‐PASE score was 8.37 (SD 7.51, range 0.00–45.00). The Pearson's correlation coefficient was 0.83 (p < 0.0001), indicating very strong and significant correlation between PASI and G2‐PASE scores. The standardized Cronbach coefficient alpha was 0.91. Results from the Canadian PSOLAR cohort are similar to those of patients enrolled at the New Lab Clinical Research Inc. site and complement findings previously reported from this site. Conclusions This study validates G2‐PASE as a reliable measure of plaque psoriasis severity when compared to PASI among a large cohort of patients with predominantly moderate to severe disease.

OBJECTIVE:To evaluate the efficacy and safety of guselkumab, an interleukin-23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) and inadequate response (inadequate efficacy and/or intolerance) to one prior tumor necrosis factor (TNF) inhibitor. METHODS:In SOLSTICE (phase 3b, randomized, multicenter, double-blind, placebo-controlled study), enrolled adults with active PsA (three or more swollen joints; three or more tender joints; C-reactive protein ≥ 0.3 mg/dL) and inadequate response to one prior TNF inhibitor were randomized to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then Q8W, or placebo with crossover to guselkumab Q4W at week 24. The primary endpoint was ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50, ACR70, Investigator's Global Assessment of psoriasis (IGA) score of 0 or 1 with ≥2-grade improvement, ≥90% improvement in Psoriasis Area and Severity Index (PASI90), and minimal disease activity (MDA) at week 24 and were analyzed by intention-to-treat. RESULTS:Analyses included 451 randomized participants (Q4W n = 150; Q8W n = 151; placebo n = 150). At week 24, significantly greater proportions of guselkumab (Q4W/Q8W)-treated participants versus placebo-treated participants, respectively, achieved ACR20 (primary endpoint: 58.6%/62.2% vs 34.8%), ACR50 (31.4%/32.1% vs 12.2%), ACR70 (17.5%/17.3% vs 2.0%), IGA 0/1 response (50.0%/57.3% vs 17.4%), PASI90 (49.4%/45.5% vs 12.0%), and MDA (18.8%/23.9% vs 5.4%) (all P < 0.001). Through week 24, 46.7%, 53.6%, and 48.3% of participants receiving guselkumab Q4W, guselkumab Q8W, and placebo, respectively, had one or more adverse event. One death occurred (myocardial infarction). CONCLUSION:Comparable efficacy was observed with both guselkumab regimens in participants with active PsA and inadequate response to one prior TNF inhibitor; safety findings were consistent with the known profile of guselkumab in patients with psoriatic disease.

Introduction The Psoriasis Longitudinal Assessment and Registry (PSOLAR; NCT00508547) is a large, international, prospective, longitudinal, disease-based registry that enrolled patients with psoriasis (PsO) who were receiving, or were candidates for, systemic therapy. The aims of the Registry are to assess the long-term safety and improve understanding of real-world biologic use in patients with PsO. Objective The objective of this analysis is to describe real-world effectiveness of guselkumab in patients with psoriasis. Methods Disease characteristics, absolute Psoriasis Area and Severity Index (PASI) score, percentage of body surface area (BSA) involvement, and change from baseline in PASI score and BSA through two years are reported for patients with PsO treated with guselkumab (GUS). Some patients initiated GUS ahead of enrolment in the registry. Results As of 12 July 2024, 2198 patients who initiated GUS prior to, or at, enrolment were included with a mean (standard deviation [SD]) duration of follow-up of 3.02 (1.08) years. Of these, 1184 (53.9%) were from North America, 672 (30.6%) were from Europe and 342 (15.6%) were from the Asia-Pacific region. Through 2 years of treatment, 244 (11.1%) patients withdrew from the registry, with the most common reason for withdrawal being patient choice (n=96, 39.3%) and 48 (19.7%) patients being lost to follow-up. Most patients had plaque PsO (2140, 97.4%) with a mean (SD) baseline PASI score of 6.0 (7.02) and a mean (SD) BSA involvement of 8.9% (12.72%). At baseline, 427 (21.1%) patients had a PASI score of 0, 188 (9.3%) had PASI >0–<1, 199 (9.8%) had PASI ≥1–<2, 160 (7.9%) had PASI ≥2–<3, 231 (11.4%) had PASI ≥3–<5 and 816 (40.4%) had PASI ≥5. Approximately 1 in 4 GUS patients had a PASI score of >10 (n=496; 24.5%). At Month 6, the mean (SD) change from baseline in PASI score was −4.5 (7.06) and the mean (SD) change from baseline in %BSA was −6.6 (12.41), corresponding to a mean (SD) absolute PASI score of 1.6 (3.10) and a mean (SD) BSA of 2.3% (5.81%), respectively. Improvements were maintained through 1 year of therapy; at Month 12, the mean (SD) change from baseline in PASI score was −4.4 (6.96) and in %BSA was −6.8 (12.26), corresponding to mean (SD) absolute PASI score of 1.5 (2.74) and a mean (SD) BSA of 1.9% (4.79%). Improvements were maintained through 2 years of treatment, with a mean (SD) absolute PASI score of 1.5 (3.13) and a mean (SD) BSA of 2.1% (6.08%), respectively. Conclusion: Patients in this large real-world registry experienced improvements in PsO severity while receiving treatment with GUS. Improvements were maintained through 2 years of treatment, supporting the use of GUS as a highly effective long-term option for patients with PsO.

Abstract Background Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. Methods The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator’s Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel–Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. Discussion Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Introduction/Objective: Data are limited on the safety of biologics in patients with a history of malignancy. We report malignancy rates in PSOLAR stratified by prior or no history of malignancy before registry entry.

Introduction/Objective: PSOLAR is a large, prospective, international, longitudinal registry evaluating long-term safety and clinical outcomes for patients eligible to receive systemic therapy for psoriasis. In 2018, PSOLAR expanded enrollment to include patients receiving guselkumab (an interleukin [IL]-23p19 subunit inhibitor) or an IL-17 inhibitor (IL-17i).

BACKGROUND:The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy.OBJECTIVES:To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR.METHODS:Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics.RESULTS:There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%).CONCLUSION:The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.

To assess changes in the Patient-Reported Outcomes Measurement Information System (PROMIS®) outcomes related to social, mental, and physical well-being after approximately 1 year of intravenous (IV) golimumab or infliximab treatment in patients with rheumatoid arthritis (RA) using real-world evidence from AWARE.AWARE was a prospective, noninterventional, multicenter, observational, U.S.-based phase 4 study of 1270 RA patients who initiated treatment with IV golimumab or infliximab. PROMIS-29 and PROMIS short form (SF) Fatigue 7a and Pain Interference 6b questionnaires were administered at baseline and infusions 2, 5, and 8 (approximately weeks 4, 28, and 52 for IV golimumab and weeks 2, 22, and 46 for infliximab). Mean changes from baseline in all PROMIS-29 domains and respective SFs and response rates for achieving ≥ 3, ≥ 5, or ≥ 10-point improvements were determined.Among all patients, baseline mean ± SD PROMIS T-scores were consistent between treatment groups and indicated worse physical function (38.2 ± 6.8 IV golimumab, 38.0 ± 6.9 infliximab), more pain interference (63.0 ± 7.6 IV golimumab, 63.9 ± 7.8 infliximab), and greater fatigue (58.4 ± 9.9 IV golimumab, 59.4 ± 10.0 infliximab) in these patients vs the general U.S. population (T-score = 50). Through the 8th infusion of either treatment, IV golimumab- and infliximab-treated patients achieved meaningful improvements (≥ 3-point improvement in T-scores) in all PROMIS-29 domains and respective SFs, and the proportions of patients with ≥ 3, ≥ 5, or ≥ 10-point improvements in T-scores increased from infusion 2 through infusion 8.RA patients treated with IV golimumab or infliximab achieved comparable improvements across social, mental, and physical well-being PROMIS measures. Additionally, PROMIS detected meaningful clinical changes in patient-reported outcomes in both treatment groups.NCT02728934.

Abstract Background Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients. Methods AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year. Results Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (− 10.2 ± 14.2 and − 10.8 ± 13.8) and golimumab without MTX (− 9.6 ± 12.9 and − 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively. Conclusions Mean change in CDAI score in the golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. Trial registration: clinicaltrials.gov NCT02728934 05/04/2016.

Introduction: The POWER study evaluated efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs placebo on a background of continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients (pts) with secondary loss of response (LoR) to standard q8w UST maintenance therapy. This subgroup analysis reports primary and major secondary endpoints up to week (W)16 in pts with/without a history of inadequate response or intolerance to prior biologics. Methods: Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR was defined as CD Activity Index (CDAI) score of ≥220 and ≤450, plus either elevated C-reactive protein (CRP; >3mg/L), fecal calprotectin (fCal; >250mg/kg), or endoscopy performed ≤3 months before W0 with evidence of active CD. At W0 randomized pts received ∼6mg/kg IV UST/SC placebo (IV arm) or IV placebo/SC UST 90mg (SC arm) followed by 90mg SC UST at W8/16. Clinical/biomarker assessments occurred at W0/8/16. Primary endpoint: W16 clinical response (CRes; decrease of ≥100 points from W0 or CDAI < 150). Secondary endpoints: CRes; clinical remission (CRem); normalization of CRP and/or fCal at W8/16. Results: The full analysis set comprised 215 pts at W0 (SC, n=107; IV, n=108). At W16, 86.0% (SC) and 92.6% (IV) of pts completed treatment. Most pts (SC, 92.5%; IV, 88.9%) had a history of inadequate response/intolerance to prior biologics. At W16, while CRes did not statistically differentiate between arms, secondary outcomes indicated a difference in the IV vs SC arm. In this analysis, differences were seen in bionaïve pts and those with inadequate response/intolerance to < 3 biologics. A numerically greater proportion of pts achieved CRes in the IV vs SC arms in all groups except pts with ≥3 prior biologics, with a nominal difference in pts with 1 prior biologic (P=0.043; Table 1). A similar trend was observed for pts achieving W16 CRem, albeit the nominal threshold was not reached. A numerically greater proportion of pts in the IV vs SC arm achieved normalization of CRP and/or fCal at W16, except those with ≥3 prior biologics, and with a nominal difference in pts with 1 prior biologic (P< 0.001). Conclusion: POWER is the first trial to assess the efficacy and safety of UST IV re-induction in pts with secondary LoR. This analysis suggests that both naïve pts and those with prior inadequate response or intolerance to biologics may benefit from UST re-induction therapy. Table 1. - Primary and major secondary endpoints at W8 and W16 for patients with or without a history of inadequate response or intolerance to prior biologic(s) (Full analysis set) Overall population No history of prior biologic* inadequate response or intolerance History of inadequate response or intolerance to 1 prior biologic* History of inadequate response or intolerance to 2 prior biologics* History of inadequate response or intolerance to ≥3 prior biologics* UST SC n=107 UST IVn=108 UST SCn=8 UST IVn=12 UST SCn=37 UST IVn=33 UST SCn=35 UST IVn=35 UST SCn=27 UST IVn=28 Clinical response†‡ at W16 (primary endpoint) 40 (37.4) 53 (49.1)Δ 11.5 (-1.5; 24.5) P=0.089 1 (12.5) 5 (41.7)Δ 29.2 P=0.325 15 (40.5) 21 (63.6)Δ 24.4 (2.0; 46.8) P=0.043 13 (37.1) 18 (51.4)Δ 16.2 (-6.2; 38.7) P=0.177 11 (40.7) 9 (32.1)Δ -8.4 (-33.2; 16.3) P=0.535 Clinical remission‡§ at W16 29 (27.1) 36 (33.3)Δ 5.9 (-6.0; 17.8) P=0.338 0 4 (33.3)Δ 33.3 P=0.117 12 (32.4) 15 (45.5)Δ 11.8 (-9.9; 33.4) P=0.313 8 (22.9) 12 (34.3)Δ 10.6 (-10.7; 31.9) P=0.334 9 (33.3) 5 (17.9)Δ -11.0 (-33.3; 11.2) P=0.359 Patients with normalized CRP and/or fCall‡ ||¶** at W16 14/94 (14.9) 31/93 (33.3)Δ 18.5 (6.8; 30.2) P=0.004 1/8 (12.5) 2/8 (25.0)Δ 12.5 P=1.00 2/31 (6.5) 12/28 (42.9)Δ 37.6 (17.9; 57.4) P< 0.001 6/30 (20.0) 12/32 (37.5)Δ 17.8 (-3.1; 38.7) P=0.131 5/25 (20.0) 5/25 (20.0)Δ 3.8 (-18.8; 26.4) P=0.743 Clinical response†‡ at W8 48 (44.9) 56 (51.9)Δ 7.1 (-6.0; 20.2) P=0.300 3 (37.5) 4 (33.3)Δ -4.2 P=1.00 21 (56.8) 20 (60.6)Δ 4.7 (-18.4; 27.7) P=0.696 12 (34.3) 19 (54.3)Δ 22.0 (-0.2; 44.3) P=0.067 12 (44.4) 13 (46.4)Δ -2.7 (-29.1; 23.6) P=0.844 Clinical remission‡§ at W8 31 (29.0) 38 (35.2)Δ 6.4 (-5.8; 18.6) P=0.314 3 (37.5) 4 (33.3)Δ -4.2 P=1.00 15 (40.5) 14 (42.4)Δ -0.2 (-22.3; 21.8) P=0.985 6 (17.1) 14 (40.0)Δ 21.5 (1.3; 41.6) P=0.049 7 (25.9) 6 (21.4)Δ -2.0 (-24.3; 20.2) P=0.864 Data are presented as n (%) Δ (95% CI) P-value P<0.05 was the threshold for significance; P-values should be considered nominal as primary endpoint was not met.*Tumor necrosis factor inhibitors or vedolizumab.†Clinical response is defined as a decrease of ≥100 points from W0 or CDAI score of <150 points.‡Patients who had insufficient data at the designated analysis timepoint or a prohibited CD-related surgery, prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be caused by worsening CD prior to the designated analysis timepoint were not considered to have achieved the endpoint.§Clinical remission is defined as CDAI <150 points.||Abnormal CRP is defined as CRP value >3 mg/L and abnormal fCal concentrations is defined as >250 µg/g.¶Normalized CRP is defined as CRP value ≤3 mg/L and normalized fCal concentrations is defined as ≤250 µg/g. When either the CRP or fCal value is abnormal at baseline and the value of the same parameter normalizes at W16, patients are considered to be normalized at the designated analysis timepoint.**Patients who had insufficient data at the designated analysis timepoint had their last value carried forward.Δ, difference; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; fCal, fecal calprotectin; IV, intravenous; SC, subcutaneous; UST, ustekinumab; W, week.

Introduction: The 36-week (W) POWER trial evaluated the efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients with secondary loss of response (LoR) to standard UST maintenance therapy. Here, we report subgroup analysis of the primary endpoint by baseline characteristics. Methods: Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR has been previously defined1. At baseline (W0), randomized patients received ∼6mg/kg IV UST/SC placebo (IV arm) or IV placebo/SC UST 90mg (SC arm), followed by SC UST 90mg dosing at W8/16. Descriptive statistics were used to summarize baseline characteristics. Clinical assessments occurred at W0/8/16. Primary endpoint: clinical response (CRes; decrease of ≥100 points from W0 in CD activity index [CDAI] or CDAI < 150) at W16. Odds ratios (ORs), confidence intervals (CIs) and P-values were estimated with a logistic regression model. Results: The full analysis set comprised 215 patients at W0 (SC, n=107; IV, n=108). At W16, 86.0% (SC) and 92.6% (IV) of patients completed treatment. At W16, 37.4% (SC) and 49.1% (IV) of patients achieved CRes (P=0.089). Of all baseline characteristics, disease location and duration, inflammatory biomarkers and prior biologic failures were of particular interest (Table 1). A greater proportion of patients from the IV vs SC arm achieved CRes at W16 (OR 3.6; 95%CI 1.6–8.1; P=0.002) of those with ileum and colon involvement. Patients with disease duration of < 5 years in the IV (n=22) vs SC (n=20) arm were more likely to achieve W16 CRes (OR 4.5; 95%CI 1.2–17.4; P=0.029). A greater proportion of patients in the IV vs SC arm with elevated baseline C-reactive protein (OR 2.1; 95%CI 1.1–4.0; P=0.029) or fecal calprotectin (OR 2.0; 95%CI 1.0–4.0; P=0.045) achieved W16 CRes as did patients with 1 prior biologic failure (OR 2.8; 95%CI 1.0–7.6; P=0.042). Conclusion: POWER assessed the efficacy and safety of UST IV re-induction in patients with LoR during UST maintenance therapy. This analysis suggests that patients with fewer prior biologic exposures and shorter disease duration but a higher disease burden at baseline including greater disease extent involving ileum and colon, or elevated inflammatory biomarkers, are more likely to benefit from UST IV re-induction therapy. 1. S.W. Schreiber, et al. J Crohns Colitis. 2023;17(Suppl 1):571 (Abstract P436). Table 1. - Proportion of patients who achieved clinical response*† at Week 16 by baseline characteristics (Full analysis set). As the primary endpoint was not met, all P-values should be considered nominal Baseline and clinical disease characteristics UST SC (n=107), n/N (%) UST IV (n=108), n/N (%) OR‡ (95%CI); P-value Age (median years) ≤40 22/62 (35.5) 28/52 (53.8) 2.1 (1.0; 4.4); P=0.060 >40 18/45 (40.0) 25/56 (44.6) 1.3 (0.6; 2.8); P=0.58 CDAI Score ≤300 24/68 (35.3) 30/68 (44.1) 1.4 (0.7; 2.9); P=0.312 >300 16/39 (41.0) 23/40 (57.5) 2.0 (0.8; 4.8); P=0.138 Prior CD-related surgery history Total or subtotal colectomy 4/9 (44.4) 7/17 (41.2) NE Partial bowel resection 12/28 (42.9) 21/39 (53.8) 1.5 (0.5; 4.0); P=0.472 Current draining fistula 2/10 (20.0) 4/11 (36.4) NE Prior perianal surgery 4/21 (19.0) 14/23 (60.9) 5.8 (1.5; 23.3); P=0.013 Involved gastrointestinal areas Ileum only 13/28 (46.4) 10/29 (34.5) 0.6 (0.2; 2.0); P=0.434 Colon only 11/22 (50.0) 10/24 (41.7) 0.7 (0.2; 2.3); P=0.505 Ileum and colon 16/55 (29.1) 33/55 (60.0) 3.6 (1.6; 8.1); P=0.002 Disease duration (years) < 5 5/20 (25.0) 13/22 (59.1) 4.5 (1.2; 17.4); P=0.029 ≥5 35/87 (40.2) 40/86 (46.5) 1.3 (0.7; 2.4); P=0.395 Prior failed biologics 0 1/8 (12.5) 5/12 (41.7) NE 1 15/37 (40.5) 21/33 (63.6) 2.8 (1.0; 7.6); P=0.042 2 13/35 (37.1) 18/35 (51.4) 2.0 (0.7; 5.3); P=0.173 3 10/25 (40.0) 6/23 (26.1) 0.6 (0.2, 2.0); P=0.363 4 1/2 (50.0) 3/5 (60.0) NE Baseline biomarker levels CRP ≤3 mg/L 12/32 (37.5) 10/29 (34.5) 0.9 (0.3; 2.5); P=0.780 CRP >3 mg/L 28/75 (37.3) 43/79 (54.4) 2.1 (1.1; 4.0); P=0.029 fCal ≤250 mg/kg 16/32 (50.0) 18/35 (51.4) 1.1 (0.4; 2.8); P=0.920 fCal >250 mg/kg 24/75 (32.0) 35/73 (47.9) 2.0 (1.0; 4.0); P=0.045 *Clinical response is defined as a decrease of ≥100 points from Week 0 or CDAI score of < 150 points.†Patients who had insufficient data at the designated analysis timepoint or a prohibited CD-related surgery, prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be caused by worsening CD prior to the designated analysis timepoint were not considered to have achieved clinical response, regardless of their CDAI score.‡OR, 95%CI for OR, and P-values were based on logistic regression.CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; fCal, fecal calprotectin; IV, intravenous; NE, not evaluated; OR, odds ratio; SC, subcutaneous; UST, ustekinumab.

Introduction: The POWER study evaluated efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients (pts) with secondary loss of response (LoR) to standard UST maintenance therapy. Here, we present Week (W) 16 pharmacokinetics, exposure–response relationships, and immunogenicity analysis. Methods: Adult pts with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR was defined as CD Activity Index (CDAI) score ≥220–≤450, plus elevated C-reactive protein ( >3mg/L)/fecal calprotectin ( >250mg/kg), or endoscopy performed ≤3 months before baseline (W0) with active CD. At W0, randomized pts received ∼6mg/kg IV UST, or SC UST 90mg, followed by SC UST 90mg dosing at W8/16. Clinical assessments occurred at W0/8/16. Serum samples evaluated UST concentration (conc) and anti-drug antibodies (ADAs) at W0/8/16 using validated assays. Clinical response (CRes) and endoscopic remission (ERem) were evaluated based on CDAI and centrally read endoscopy, respectively, at W0/8/16. Efficacy outcomes were analyzed by W0 trough conc groups (undetectable, 0.17–< 0.8, 0.8–< 1.3, and ≥1.3µg/mL) and conc quartile groups (QGs) at W16 using a proprietary immunoassay. Results: Serum UST conc data were obtained from 215 pts (SC, n=107; IV, n=108) with ≥1 blood sample collected. Similar at W0, median serum UST concs at W0 (1-hour post-dose)/8/16 were higher in the IV vs SC arm (Table 1). Based on W16 trough concs, 63.9% (69/108) of pts were in the ≥1.3µg/mL group in the IV arm, vs 41.1% (44/107) in the SC arm. The proportion of pts with W16 CRes in the ≥1.3µg/mL group was similar between arms; more pts were in W16 ERem in the IV vs SC arm. By W16 quartile analysis, CRes was numerically higher in the IV vs SC arm in QG1 and 4. More IV arm pts achieved ERem in QG4 vs QG1; a small number of pts in SC arm achieved ERem independent of QGs. Incidence of UST ADAs through W16 was low (SC, n=2; IV, n=0; 0.93% overall). Conclusion: Although, IV re-induction resulted in higher serum concs and proportions of pts with high (≥1.3µg/mL) trough conc at W16; there did not appear to be an exposure-response relationship for CRes. However, quartile analysis showed a relationship between increased exposure in the IV arm and differences in ERem. This observation is consistent with the notion that pts with secondary LoR may benefit from single-dose re-induction. Table 1. - Summary of serum UST concentrations and the proportion of patients in clinical response and endoscopic remission at W16 by UST trough concentrations and trough concentration quartile groups at W16 (full analysis set) Serum concentrations µg/mL (median, IQR) SC arm (N=107) IV arm (N=108) W0 pre-dose 1.26 (0.58; 2.53) 1.30 (0.62; 2.79) W0 post-dose* 1.47 (0.70; 2.62) 105.62 (82.94; 128.13) W8 1.38 (0.85; 2.61) 8.45 (4.25; 10.49) W16 1.41 (0.81; 2.17) 2.99 (1.20; 4.78) W16 outcomes by UST trough concentrations at W16 (µg/mL), n/N (%) Undetectable 0.17–< 0.8 0.8–< 1.3 ≥1.3 Undetectable 0.17–< 0.8 0.8–< 1.3 ≥1.3 Clinical response†‡ at W16 0/1 5/18 (27.8) 8/16 (50.0) 24/44 (54.5) 0/2 8/15 (53.3) 3/7 (42.9) 39/69 (56.5) Endoscopic remission‡§|| at W16 0/1 0/9 1/7 (14.3) /24 (8.3) 0/1 1/6 (16.7) 0/4 10/42 (23.8) W16 outcomes by UST trough concentration quartile groups¶ at W16, n/N (%) QG1 (≤q1) QG2 ( >q1 and ≤q2) QG3 ( >q2 and ≤q3) QG4 ( >q3) QG1 (≤q1) QG2 ( >q1 and ≤q2) QG3 ( >q2 and ≤q3) QG4 ( >q3) Clinical response†‡ by QG 5/20 (25.0) 11/20 (55.0) 12/20 (60.0) 9/19 (47.4) 11/24 (45.8) 11/23 (47.8) 13/23 (56.5) 15/23 (65.2) Endoscopic remission‡§|| by QG 0/10 1/11 (9.1) 0/9 2/11 (18.2) 1/11 (9.1) 2/10 (20.0) 3/14 (21.4) 5/18 (27.8 *The post-dose sample was collected within 24 hours of UST administration.†Clinical response is defined by CDAI <150 or decrease of ≥100 points from W0.‡Patients who had insufficient data to calculate CDAI or SES-CD, a prohibited CD-related surgery, prohibited concomitant medication changes, or discontinued study agent due to lack of efficacy or due to an adverse event indicated to be of worsening CD prior to the designated analysis timepoint are considered not to be in clinical response or endoscopic remission.§Endoscopic remission is defined as an SES-CD score ≤3 or SES-CD=0 for patients who enter the study with an SES-CD=3.||Endoscopy was an optional procedure in the study; only 58 (SC arm) and 59 (IV arm) patients were included in the endoscopic analysis.¶Quartiles are based on patients in each treatment group: SC arm, q1=0.81 µg/mL, q2=1.41 µg/mL, q3=2.17 µg/mL; IV arm, q1=1.20 µg/mL, q2=2.99 µg/mL, q3=4.78 µg/mL. CD, Crohn’s Disease; CDAI, Crohn’s Disease Activity Index; IQR, interquartile range; IV, intravenous; q, quartile; QG, quartile group; SC, subcutaneous; SES-CD; Simple Endoscopic Score in Crohn’s Disease; UST, ustekinumab; W, week.

Abstract Background After successful induction, a subset of patients with Crohn’s disease (CD) experience a secondary loss of response (LoR) to ustekinumab (UST) maintenance therapy. Dose intensification may assist in regaining response. The phase 3b randomised, double-blind, multicentre POWER study evaluated efficacy and safety of a single intravenous (IV) re-induction UST dose vs continued UST subcutaneous (SC) treatment in CD patients with LoR to standard UST every 8 weeks (q8w) maintenance therapy. Methods Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and subsequently experienced LoR were included. LoR for inclusion was defined as CDAI score of ≥220 and ≤450, in addition to elevated CRP (>3mg/L), fCal (>250mg/kg) or endoscopy performed ≤3 months before W0 with evidence of active CD (≥1 ulcerations in the ileum and/or colon). At baseline (W0), randomised patients received either ~6mg/kg IV UST/SC placebo (IV arm), or IV placebo/SC UST 90mg (SC arm), followed by SC UST 90mg dosing in both groups at W8/16. Clinical and biomarker assessments were made at W0/8/16 and optional ileocolonoscopy at W0/16. Primary endpoint: clinical response (CRes; decrease of ≥100 points from W0/CDAI <150) at W16. Additional outcome measures included clinical, biomarker, endoscopic and quality of life endpoints assessed at W8/16. Results The analysis set comprised 215 patients at W0 (IV, n=108; SC, n=107). At W16, 92.6% and 86.0% completed treatment from IV and SC arms, respectively. In both arms (IV, 58.3%; SC, 57.9%) most patients experienced ≥2 biologic failures before initiating UST (Table 1). At W16, 49.1% in the IV arm and 37.4% in the SC arm achieved CRes (p=0.089). Percentages of patients with normalisation of fCal, normalisation of CRP and/or fCal, endoscopic remission and improvement, and improvement in IBDQ score were greater in the IV vs SC arm (Table 2). At W16, similar proportions of patients had ≥1 adverse event (AE) (IV, 60.2%; SC, 61.7%) and serious AEs (IV, 5.6%; SC, 5.6%). The proportions of patients with infections were similar between arms (IV, 23.1%; SC, 21.5%), with only 1 serious infection in each arm. Conclusion POWER is the first randomised, controlled, double-blind trial to assess the efficacy and safety of UST IV re-induction in patients with LoR during UST maintenance therapy. The CDAI-based primary endpoint at W16 was not met. However, patients in this heavily pre-treated population who received IV re-induction showed clinically meaningful improvements at W16 compared with those receiving SC, particularly for objective endpoints, including inflammatory biomarkers and endoscopic outcomes.

Psoriasis is a chronic inflammatory disease affecting 3% of the US population (Armstrong et al., 2021). The negative effect of psoriasis on health-related QOL is similar to that of other serious chronic diseases (Rapp et al., 1999). Data on the QOL burden of psoriasis among non-White populations are limited. This study evaluated racial/ethnic differences in the effect of psoriasis on health-related QOL, as measured by the Dermatology Life Quality Index (DLQI), among North American patients with psoriasis enrolled in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Background: Patterns of psoriasis characteristics by sex are not fully understood. Objective: Evaluate patient characteristics by sex at enrollment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: Two PSOLAR cohorts were evaluated by sex: patients who were biologic-naïve (n = 3329) and patients who were systemic therapy-naïve (n = 1290) at entry. Baseline demographic and disease characteristics, medical history, social activity, and lifestyle risk factors were collected for all patients and were compared between males and females using an independent samples t-test for continuous variables and chi-square tests for categorical variables. Results: In both cohorts, disease duration was similar for males and females; however, disease severity based on baseline Physician Global Assessment and body surface area of psoriasis was greater in males versus females ( P < .05). Baseline Dermatology Life Quality Index scores were higher for biologic-naïve females than for males ( P = .008). In both cohorts, females were significantly more likely than males to have a history of anxiety, depression, and cancer excluding nonmelanoma skin cancer, to have received systemic steroid therapy, and to have health insurance; males were significantly more likely than females to have a history of cardiovascular disease, smoking, and alcohol consumption, and to work full time. Conclusions: Based on patient data obtained at entry into PSOLAR, significant differences in psoriasis disease characteristics, and medical, family, and social history-related variables were observed between males and females. Among systemic therapy-naïve patients, there was a greater negative impact on quality of life for females compared with males, despite generally lower objective disease severity for females.