Daphne Chan

A Canadian online survey to evaluate awareness and treatment satisfaction in individuals with moderate to severe plaque psoriasis.

Background  Psoriasis is a chronic inflammatory disease associated with comorbidities and decreased quality of life. This survey is aimed to better understand the impact of disease on Canadian patients, and to examine awareness and use of available treatment options.

A Canadian Self-Administered Online Survey to Evaluate the Impact of Moderate-to-Severe Psoriasis among Patients

Background: Few population studies of individuals living with psoriasis have been performed in Canada. Objective: The objective of this survey was to understand the severity and impact of psoriasis on the lives of Canadian patients. Methods: An online survey was conducted using a consumer panel. Eligible subjects reported a diagnosis of psoriasis and provided a self-reported level of severity. In addition, subjects had to either (a) have psoriasis covering at least 3% of their body surface area; (b) have psoriasis on a sensitive area of the body; or (c) be currently undergoing treatment for their psoriasis with systemic medication and/or phototherapy. Results: A total of 514 panelists met the inclusion criteria and completed the survey. Current moderate, severe, or very severe psoriasis was reported by 65% of respondents. Nearly all subjects (96%) had psoriasis affecting a sensitive area of the body. At the time of the survey, 18% were taking systemic medication and/or phototherapy. Comorbidities, such as obesity and high blood pressure, were highly prevalent, with 75% of respondents reporting at least one other diagnosis. Data from the SF-8 and Dermatology Life Quality Index instruments indicated that psoriasis negatively impacted quality of life. Conclusion: Moderate-to-severe psoriasis places a burden on Canadian patients, some of whom may be receiving suboptimal treatment or treatment not appropriate for the severity of their condition.

Sa1211 Assessment of Sleep Impairment in Patients With Crohn's Disease: Results From the Ustekinumab Certifi Study

Introduction To describe the extent of sleep impairment reported in CERTIFI (Ph2 evaluating UST in inducing & maintaining clinical response & remisison)using Jenkins Sleep Evaluation Questionnaire (JSEQ) & establish a clinically meaningful improvement threshold for JSEQ. Methods Pts with moderate-to-severe CD(CDAI ≥220 & ≤450) who had previously failed or were intolerant to ≥1 anti-TNF were randomised to PBO/UST induction at wk0. Primary endpt was clinical response (≥100-pt reduction in CDAI from BL) at wk6. Sleep impairment assessed using JSEQ (total score 0–20; higher scores indicate greater sleep impairment) at BL&wk6. Relationships between BL sleep impairment, clinical disease activity (CDAI), & HRQoL impact(IBDQ) evaluated using Pearson correlation. Clinically meaningful improvement threshold of JSEQ was established with the anchor-based [clinical response by reduction in CDAI of ≥70-pt or clinically meaningful improvement (≥16-pt) in IBDQ] & distribution-based (change by one-half of the standard deviation [SD] of BL JSEQ score) methods. Prop of pts who achieved clinically meaningful improvements in JSEQ at wk6 was determined & compared. Results At BL,both grps(n = 526) experienced similar degree of moderate sleep impairment, with JSEQ scores (mean±SD) of 11.0 ± 4.30(PBO)&11.0 ± 4.59(UST),resp. About 60% were “waking up feeling tired and worn out”; about 30–35% of pts had trouble falling asleep, staying asleep,& woke up several times during the night for 15–30 days in the previous month. At BL, JSEQ was correlated with CDAI (r = 0.19, p 2 or > 3 points from BL JSEQ score at wk6) were derived. More pts who received UST induction achieved both thresholds at wk6(Table). Conclusion Pts experience significant sleep problems as measured by JSEQ; magnitude of impairment correlates with disease activity. Both anchor- &distribution-based methods derive similar thresholds representative of clinically meaningful improvements in JSEQ. UST induction resulted in a greater proportion of pts achieving clinically meaningful improvements in sleep impairments. Disclosure of Interest C. Gasink Employee of: Janssen R&D, LLC, D. Chan Employee of: Janssen R&D, LLC, L.-L. Gao Employee of: Janssen R&D, LLC, B. Schenkel Employee of: Janssen Scientific Affairs, LLC, C. Han Employee of: 3. Janssen Pharmaceutical Services

Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit

Background: Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumor necrosis factor agent, in moderately-to-severely active pediatric patients with UC refractory to conventional therapy. Methods: We report a multicenter, open-label study of golimumab with a pharmacokinetics phase (week 0–14). Patients had moderately-to-severely active UC and were naive to anti-tumor necrosis factor treatment. At weeks 0 and 2, patients received golimumab induction dosed by weight (<45 kg [90/45 mg/m2]; ≥45 kg [200/100 mg]). Week 6 clinical responders continued golimumab q4w. Serum golimumab concentrations, clinical outcomes (Mayo score, PUCAI score), and adverse events are reported. Results: Thirty-five patients (71.4% pancolitis) aged 6 to 17 years had baseline median (interquartile range), age, weight, and disease duration of 15.0 (11.0–16.0) years, 50.6 (35.2–59.0) kg, and 1.2 (0.6–3.1) years, respectively. Baseline Mayo and PUCAI scores were 8.0 (6.0–9.0) and 45 (35.0–65.0), respectively. Median (interquartile range) serum golimumab concentrations were comparable to a historical reference adult UC population at weeks 2 (5.72 [3.80–9.17] &mgr;g/mL), 4 (7.61 [3.22–9.51] &mgr;g/mL), and 6 (2.64 [0.92–3.83] &mgr;g/mL). Serum golimumab concentrations were generally lower in the <45 kg than ≥45 kg weight subgroup. At week 6, 60%, 34%, and 54%, of patients achieved Mayo clinical response, PUCAI clinical remission, and mucosal healing (Mayo subscore 0/1). No clinically important safety concerns were reported. Conclusions: This open-label study demonstrates that pediatric and adult golimumab pharmacokinetics are similar. Clinical benefit and safety shows promise in biologically naive pediatric patients with UC.

Efficacy of Ustekinumab for Induction and Maintenance of Histological Healing in patient's with Crohn’s Disease

Introduction Ustekinumab (UST) has been shown to induce and maintain clinical response and remission and to produce clinically meaningful endoscopic improvement in patients with moderate-severe Crohn’s disease (CD). Effects of UST on histologic CD activity were evaluated in a substudy of the induction (UNITI-1 and 2) and maintenance (IM-UNITI) Phase 3 studies. Method Biopsies were taken at induction baseline(I-Wk0), Wk8(I-Wk8), and maintenance Wk44(M-Wk44) from 3 sites (ileum, splenic flexure, rectum) and blindly scored by an expert GI pathologist (GDH) using the Global Histology Activity Score (GHAS1). At I-Wk0, pts received a single IV dose (UST 130 mg, UST~6 mg/kg, or PBO). At I-Wk8, UST induction responders were re-randomised to subcutaneous (SC) PBO, UST 90 mg q12w or UST 90 mg q8w. Histology data from 251 substudy pts with simple endoscopic score for CD (SES-CD)≥3 at I-Wk0 were eligible for analysis. The relationship between GHAS and SES-CD was evaluated by Spearman correlation. Histologic improvements were assessed within groups (UST, PBO) and between groups (UST vs. PBO, at I-Wk0, I-Wk8 and M-Wk44). Results Regional and overall GHAS were moderately correlated with SES-CD at all timepoints (r~0.6, p Conclusion Histologic and endoscopic disease activities were moderately correlated. Consistent with previously reported results, statistically significant histologic improvements were observed in pts induced with UST, but not PBO. Trends for greater and continued histologic improvement were observed in pts who received UST 90 mg q8w maintenance. Disclosure of Interest K Li Conflict with: Janssen R and D, D Chan Conflict with: Janssen R and D, P Pollack Conflict with: Janssen R and D, D Jacobstein Conflict with: Janssen R and D, C Brodmerkel Conflict with: Janssen R and D, C Gasink Conflict with: Janssen R and D, B Feagan: None Declared, W Sandborn: None Declared, P Rutgeerts: None Declared, G De Hertogh: None Declared

P-097 A Multicenter Open-Label Study Assessing Pharmacokinetics, Efficacy, and Safety of Subcutaneous Golimumab in Pediatric Subjects with Moderately-Severely Active Ulcerative Colitis

Background:Pediatric patients with moderate-to-severe ulcerative colitis (UC) who fail 5-aminosalicylates, corticosteroids, and immunomodulators have limited alternative approved treatment options. Golimumab is a subcutaneous (SC) anti-tumor necrosis factor (anti-TNF) agent that has the potential to offer such patients a safe, effective, and convenient treatment option. Methods:This is a multicenter open-label study with a pharmacokinetic (PK) portion (week 0-14) and a study extension (weeks 14–126); we report here results through week 14. Subjects aged 2 to 17 years with moderate-to-severe UC (Mayo score 6–12, endoscopy subscore ≥2) who failed previous therapy as noted above and were naive to anti-TNF treatment were enrolled. Subjects received SC golimumab induction at week 0/2 by weight (<45 kg [90/45 mg/m2]; ≥45 kg [200/100 mg]). At week 6, Mayo clinical responders continued golimumab maintenance q4w (<45 kg [45 mg/m2]; ≥45 kg [100 mg]). Key outcome measures included PK and immunogenicity (serum golimumab concentrations, PK parameters, antibodies to golimumab), efficacy (Mayo score, Pediatric Ulcerative Colitis Activity Index (PUCAI) score), and safety (adverse events [AEs], serious AEs, AEs leading to discontinuation). Results:Thirty-five subjects enrolled and received ≥1 dose of golimumab. At baseline, the mean ± SD age, weight, and duration of disease were 13.4 ± 3.2 years (Range 6–17), 51.7 ± 22.7 kg (Range 19.7–134.0) and 2.4 ± 3.1 years (Range 0.2–16.0), respectively. Subjects had moderate-to-severe disease activity (mean ± SD: Mayo score 8.1 ± 1.8 [Range 6–12], PUCAI score 48 ± 17 [Range 15–80], CRP level 10.1 ± 23.9 mg/L [Range 0.1–116.0]). Most (71.4%) had extensive colonic involvement and 85.7% received ≥1 concomitant UC medications at baseline: corticosteroids including budesonide (37.1%), immunomodulators (57.1%), and 5-ASAs (65.7%). At weeks 2, 4, and 6, mean serum golimumab concentrations were 6.5, 6.5, and 2.6 &mgr;g/mL, respectively, which were similar to those observed in adults who received 200/100 mg induction. At week 6, 60% and 42.9% of subjects achieved clinical response (Mayo score decrease ≥30% and ≥3 points, rectal bleeding subscore decrease ≥1 or absolute subscore ⩽1) and clinical remission (Mayo score ⩽2, no individual subscore >1), respectively, and 34.3% achieved PUCAI remission (PUCAI <10). Mucosal healing as evaluated by sigmoidoscopy/colonoscopy at week 6 (Mayo endoscopy subscore ⩽1) was achieved in 54.3% of subjects and 22.9% achieved complete healing (Mayo endoscopic subscore 0). Parallel substantial reductions in objective biomarkers of inflammation (CRP, calprotectin, lactoferrin) were observed from baseline to week 6. Among Week 6 Mayo clinical responders who received q4w golimumab maintenance, 57.1% were in PUCAI remission at week 14. Through week 14, 94.3% of subjects reported ≥1 AE and 8.6% had an AE leading to discontinuation. Infections were reported in 37.1% of subjects, none were serious. Injection site reactions were reported in 17.1% of subjects, all were mild. Three subjects were positive for antibodies to golimumab. Eleven subjects (31.4%) reported 13 SAEs, including UC flare (n = 10) and one event each of abdominal pain, iron deficiency anemia, and acute pancreatitis. No opportunistic infections, malignancies or deaths were reported. Conclusions:Golimumab was generally well tolerated in this small open-label study of pediatric subjects with UC. The PK, efficacy, and safety outcomes observed were comparable with those previously reported in the golimumab adult UC phase 3 trials.