Prior Inadequate Response Research Articles

S575 Dupilumab Efficacy in Children With Eosinophilic Esophagitis and Prior Use of or Prior Inadequate Response, Intolerance, or Contraindication to Swallowed Topical Corticosteroids: Results From the Phase 3 EoE KIDS Study

S575 Dupilumab Efficacy in Children With Eosinophilic Esophagitis and Prior Use of or Prior Inadequate Response, Intolerance, or Contraindication to Swallowed Topical Corticosteroids: Results From the Phase 3 EoE KIDS Study

578. DUPILUMAB EFFICACY IN EOSINOPHILIC OESOPHAGITIS PATIENTS TREATED WITH PRIOR THERAPY AND INADEQUATE RESPONSE, INTOLERANCE, OR CONTRAINDICATION TO SWALLOWED TOPICAL CORTICOSTEROIDS

Abstract Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, <15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and <15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.

Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52-Week Results From Two Phase 3 Studies.

The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline. We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation. Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab. Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX.

Response rates to second-line treatment with daratumumab bortezomib dexamethasone (DVD) in relapsed/refractory light chain amyloidosis (AL) after initial Bortezomib-based regime.

Bortezomib is regularly used as frontline therapy for systemic AL amyloidosis. We assess the efficacy of second-line daratumumab-bortezomib-dexamethasone (DVD) in AL amyloidosis in bortezomib-exposed patients. A total of 116 patients treated with second-line DVD were identified from a prospective observational study of newly diagnosed AL amyloidosis (ALchemy). DVD was initiated in both the relapsed setting or where there was an inadequate response defined as very good partial response (VGPR) or VGPR with organ progression/lack of organ improvement. A complete response (CR)/VGPR to second-line DVD was achieved in 81 (69.8%) patients. A CR/VGPR was achieved in 67 (79.7%) in those who achieved a VGPR/CR to first line versus 14/32 (43.8%) in those who did not. Where DVD was initiated due to an inadequate response to first line (vs. at relapse), the median event-free survival (EFS) was 18 vs. 34 months (p = 0.002). If a CR/VGPR was achieved to DVD, the 2-year EFS was still lower in those with prior inadequate response 54% vs. 66% (p = 0.062). DVD is an efficacious second-line treatment in systemic AL amyloidosis in a bortezomib-exposed population. However, the response to DVD is poorer in those with an inadequate response to first-line bortezomib.

A Dutch cost-effectiveness analysis of fremanezumab versus best supportive care in patients with chronic migraine and inadequate response to prior preventive therapy

BackgroundChronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model.MethodsThe base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2–4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted.ResultsOver a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses.ConclusionIn comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.

EMERGE Study: An Open-label Evaluation of the Efficacy and Safety of AXS-07 (MoSEIC™ meloxicam-rizatriptan) for Migraine in Adults with Prior Inadequate Response to an Oral CGRP Inhibitor (P6-12.006)

EMERGE Study: An Open-label Evaluation of the Efficacy and Safety of AXS-07 (MoSEIC™ meloxicam-rizatriptan) for Migraine in Adults with Prior Inadequate Response to an Oral CGRP Inhibitor (P6-12.006)

Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL

ObjectivesTo assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors.MethodsPatients completing the 16-week phase III double-blind,...

P1040 Comparative effectiveness of upadacitinib versus ustekinumab in patients with moderately to severely active Crohn’s disease: a matching-adjusted indirect comparison

Abstract Background Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL 12/23 antagonist, are effective treatments for moderately to severely active Crohn’s Disease (CD). In the absence of head-to-head data, a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) was conducted to indirectly compare efficacy of UPA vs UST. Methods Individual patient (pt)-level data from phase 3 UPA trials and published data from phase 3 UST trials were used. For induction, pts received UPA 45mg daily or PBO for 12 weeks or UST ~6mg/kg IV or PBO IV at week 0 with 8-week follow-up. For maintenance, UPA clinical responders were re-randomized to UPA 15mg, 30mg, or PBO daily for 52 weeks. UST clinical responders were re-randomized to 90mg SC (every 8 or 12 weeks) or PBO SC for 44 weeks. UPA pts had baseline (BL) CD Activity Index (CDAI) 220-450; those with prior UST or vedolizumab exposure were excluded. Treatment effect modifiers, including BL mean CDAI, Simple Endoscopic Score for CD (SES-CD), median C-reactive protein, prior biologic(s) failure, and disease location, from UPA data were weighted to match the UST population. Outcomes assessed were CDAI response (≥100-point decrease or CDAI <150), CDAI remission (CDAI <150), endoscopic response (SES-CD ≥50% decrease), and SES-CD ≤2. Separate MAICs were conducted for induction and maintenance; data reported for induction clinical outcomes are stratified by prior inadequate response to tumor necrosis factor inhibitors (TNFi-IR). Results A greater proportion of UPA- vs UST-treated pts achieved endoscopic response (difference 26.3%, P<0.001) and SES-CD ≤2 (difference 9.9%, P<0.05) at the end of induction. In TNF-IR patients, a greater proportion of UPA- vs UST-treated pts achieved CDAI response at the end of induction (difference 18.2%, P<0.05) and at the end of Week 8 (difference 26.0%, P<0.001). CDAI remission rates were also higher at end of Week 8 for UPA- vs UST-treated pts (difference 13.3%, P<0.05). Rates of achieving CDAI response and remission were similar between UPA- and UST-treated pts at the end of induction and Week 8 among bio-naïve pts. Following maintenance treatment, similar rates of SES-CD ≤2, endoscopic response, and CDAI remission were obtained in the total population of UPA and UST-treated pts. Conclusion Pts with moderately to severely active CD treated with UPA achieved higher rates of endoscopic (total population) and clinical (TNFi-IR population) outcomes during induction compared to UST-treated pts. Outcomes at the end of maintenance were similar for UPA and UST, however, results should be interpreted with caution due to low sample size.

Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study

ObjectiveTo assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical...

Efficacy and safety of tofacitinib in patients with rheumatoid arthritis by previous treatment: post hoc analysis of phase II/III trials

BackgroundThis study sought to evaluate the efficacy and safety of tofacitinib in patients with rheumatoid arthritis with distinct treatment histories.MethodsPooled phase II/III trial data from patients who received tofacitinib 5 or 10 mg twice daily or placebo, as monotherapy or with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), were analyzed post hoc. Separate evaluations were conducted for populations with a prior inadequate response (IR) to: 1) non-methotrexate (MTX) csDMARDs only (non-MTX csDMARD-IR; n = 537); 2) MTX (MTX-IR; n = 3113); and 3) biologic (b)DMARDs (bDMARD-IR; n = 782). Efficacy outcomes included rates of response (American College of Rheumatology 20/50/70% response criteria) and remission (Disease Activity Score in 28 joints derived from 4 measures, erythrocyte sedimentation rate [DAS28-4(ESR)] < 2.6) at month 3, and changes from baseline in DAS28-4(ESR) and Health Assessment Questionnaire–Disability Index scores. Safety was assessed up to month 24.ResultsAt month 3, efficacy was generally improved with tofacitinib (both doses) vs placebo in each population. Generally, efficacy outcomes with tofacitinib were numerically more favorable in non-MTX csDMARD-IR vs MTX-IR or bDMARD-IR patients. Over 24 months, crude incidence rates for adverse events (AEs), serious AEs, and discontinuations due to AEs were generally numerically lower in non-MTX csDMARD-IR and MTX-IR vs bDMARD-IR populations; rates for AEs of special interest were generally similar across populations.ConclusionsTofacitinib provided clinical benefit across patients with rheumatoid arthritis with a range of prior treatment experience but may have greater efficacy and an improved benefit/risk profile in those with fewer prior treatments.Trial registrationNCT00147498/NCT00413660/NCT00550446/NCT00603512/NCT00687193/NCT00976599/NCT01359150/NCT00847613/NCT00814307/NCT00853385/NCT00960440/NCT01039688/NCT00856544.

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study

The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n= 101; 400 mg, n= 107; placebo, n= 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety wassimilar among guselkumab and placebo groups. Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. gov number: NCT04033445.

Filgotinib Modulates Inflammation-Associated Peripheral Blood Protein Biomarkers in Adults with Active Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate.

Our aim was to evaluate protein biomarker changes related to the administration of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) with inadequate response to methotrexate. Plasma and serum samples were collected from patients enrolled in FINCH 1 (NCT02889796), a Phase 3 trial. Patients with stable backgrounds of methotrexate were randomly assigned once-daily oral filgotinib 200 or 100mg, subcutaneous adalimumab 40mg every 2weeks (W), or placebo. Up to 35 biomarkers were analyzed at baseline, W4, and W12 with enzyme-linked immunosorbent assays and chemiluminescence and electrochemiluminescence assays. At baseline, four distinct biomarker clusters were identified. The strongest intragroup correlations were in bone-cartilage resorption/inflammation and JAK/signal transducer and activator of transcription (STAT) signaling activity. At baseline, significant positive correlations were identified for cytokines with patient-reported pain and with patient measures of fatigue. Filgotinib reduced levels of cytokines associated with inflammation and cell migration as early as W4 and through W12. Compared to adalimumab, filgotinib induced significant reductions in bone-related turnover biomarkers, N-telopeptide of type 1 collagen and C-telopeptide 1, as well as biomarkers associated with baseline disease activity. No baseline predictors of therapeutic response to filgotinib were identified. Filgotinib reduced peripheral protein biomarkers associated with JAK/STAT signaling, inflammatory signaling, immune cell migration, and bone resorption as soon as W4 in FINCH 1. Effects were dose-dependent and consistent with the clinical efficacy of filgotinib observed in FINCH 1. The changes in peripheral biomarkers associated with filgotinib treatment in methotrexate-experienced patients are consistent with changes observed in both methotrexate-naïve and biologic disease-modifying antirheumatic drug-experienced RA populations. These data demonstrate dose-dependent effects of preferential JAK1 inhibition by filgotinib on peripheral blood protein biomarkers in methotrexate-experienced patients with RA. ClinicalTrials.gov, NCT02889796.

The impact of C-reactive protein levels on the effectiveness of upadacitinib in patients with rheumatoid arthritis: a 12-month prospective, non-interventional German study.

We investigated whether the effectiveness of upadacitinib in rheumatoid arthritis (RA) treatment is affected by baseline CRP levels in a real-world setting. UPwArds was a prospective, non-interventional study. Patients had moderate-to-severe RA and an inadequate response or intolerance to ≥1 disease-modifying anti-rheumatic drug (DMARD). The primary endpoint was clinical remission (Clinical Disease Activity Index [CDAI] ≤2.8) at 6 months. Secondary endpoints at 12 months included clinical remission and low disease activity assessed by CDAI and Simple Disease Activity Index criteria, DAS28-CRP <2.6/≤3.2, and patient-reported outcomes. The impact of baseline CRP levels (normal vs. above the upper limit of normal [ULN]) on primary and secondary endpoints was evaluated. The effect of concomitant MTX and prior inadequate response to biologic or targeted synthetic DMARDs (b/tsDMARD-IR) on the effectiveness of upadacitinib was also assessed. Safety was evaluated through 12 months. 518 patients were included in the effectiveness analyses. At 6 months, 24.4% of patients achieved the primary endpoint (CDAI ≤2.8). At 12 months, similar proportions of patients with normal CRP and CRP above the ULN at baseline achieved CDAI ≤2.8 (27.3% and 29.1%) and other key secondary endpoints. The effectiveness of upadacitinib was comparable with and without concomitant MTX and in b/tsDMARD-naive and b/tsDMARD-IR patients. The safety results were consistent with the known safety profile of upadacitinib; no new safety signals were identified. Upadacitinib therapy was effective for RA in a real-world setting. Baseline CRP levels had no significant impact on the effectiveness of upadacitinib.

Biologic Therapy in Inflammatory Bowel Disease - Results from a Single Tertiary Care Center in North Macedonia.

Medical therapies used for Inflammatory Bowel Disease (IBD) include conventional (e.g. 5-aminosalicylates, steroids, immunomodulators) and biologic (e.g. inhibitors of tumor necrosis factor - alpha, integrin inhibitors, interleukin inhibitors) medications. Biologics, due to their high cost, were unfortunately not covered by the public health insurance system in North Macedonia until 2019 and, therefore, not widely utilized for our IBD patients. In 2019, the University Clinic of Gastroenterology and Hepatology in Skopje developed a biologic therapy supply, provided by the National Health Insurance Fund, making this therapy available for a larger number of patients. This report presents the initial results of our prospective, single tertiary-care center study on the effects of biologic therapy in patients with IBD in North Macedonia. The study is focused on the evaluation of clinical outcomes after anti-tumor necrosis factor alpha (anti TNF-alpha) therapy in IBD patients with prior inadequate response to conventional medications.

Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort.

Ixekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting. This retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized. Among the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was -1.2 (5.5) and -1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points. Treatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.

P134 Efficacy of Upadacitinib on Psoriatic Arthritis with Axial Involvement Defined by Investigator Assessment and PRO-Based Criteria: Results from two Phase 3 Studies

P134 Efficacy of Upadacitinib on Psoriatic Arthritis with Axial Involvement Defined by Investigator Assessment and PRO-Based Criteria: Results from two Phase 3 Studies

P189 Bimekizumab in patients with psoriatic arthritis with prior inadequate response to TNF inhibitors: improvements of PsARC over 16 weeks in the Phase 3 BE COMPLETE trial

Abstract Background/Aims Bimekizumab (BKZ) is a humanised monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A and has demonstrated clinical effectiveness in both joint and skin outcomes in patients with active psoriatic arthritis (PsA). Psoriatic Arthritis Response Criteria (PsARC) is used routinely for drug reimbursement in clinical practice in the UK. We report PsARC response rates along with HRQoL estimates at week (wk) 16 in TNF inadequate responder (TNFi-IR) patients with active PsA from the phase 3, 16-wk BE COMPLETE trial (NCT03896581). Methods BE COMPLETE is a randomised, multicentre, double-blind, placebo (PBO)-controlled, parallel group study. Patients who had an inadequate response or intolerance to treatment with 1 or 2 TNFis were randomised (2:1) to BKZ 160 mg every 4 wks (Q4W) or PBO for 16 wk. We report response rates for PsARC at wk 16, and the association of PsARC responders with HRQoL-related outcomes for the randomised set. Data are reported as non-responder imputation (NRI) and observed cases. Results 400 patients were randomised at baseline (BKZ: 267; PBO: 133). Baseline characteristics were comparable between groups (mean age: 50.5 yrs; BMI: 29.8 kg/m2; disease duration: 9.5 yrs and 47.5% were male). At wk 16, PsARC response (NRI) was achieved by 85.4% with BKZ and 30.8% with PBO (Table). Numerically greater improvements in physical functioning and fatigue measure were achieved from baseline among PsARC responders compared to non-responders (Table). Over 16 wks, safety was in line with previous BKZ studies and no new safety signals were observed. Conclusion In patients with prior TNFi-IR with active PsA, BKZ treatment demonstrated a greater improvement in musculoskeletal symptoms at wk 16 compared to PBO. Patients with PsARC response had numerically greater improvements in HRQoL and improvements in fatigue measures. No new safety signals were observed. Disclosure P. Sharma: Other; PS has received conference sponsorship Amgen 2015 for National Osteoporosis Conference; Janssen Advisory Board board Nov 22. D.R. Jadon: Other; DRJ received research/education grants/honoraria: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Fresenius Kabi, Gilead, GSK, Healthcare Celltrion, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. D. McGonagle: Grants/research support; DM has received research grants/research support from AbbVie, Celgene, Janssen, Merck, and Pfizer. Other; DM has recevied honoraria or consultation fees and has been paid as a speaker for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer, and UCB Pharma. B. Ink: Shareholder/stock ownership; BI is a shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. D. Assudani: Shareholder/stock ownership; Employee and shareholder of UCB Pharma. V. Taieb: Other; VT is employee of UCB Pharma. L.C. Coates: Consultancies; LCC has worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; LCC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma.

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

Objectives To assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).Methods In this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP)) &lt;3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.Results In 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p&lt;0.01 for both comparisons). Achievement of DAS28 (CRP) &lt;3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patientreported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.Conclusions Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNFi-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.

P493 QUASAR Induction Study 1 Cumulative Response to Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis

Abstract Background Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission at Week (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Methods Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore ≥2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV→GUS 200mg IV; GUS 200mg IV→GUS 200mg SC; GUS 400mg IV→GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure 1). Matching IV or SC PBO was administered to maintain the blind. Results Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. At Wk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6% (29/105) of patients randomized to PBO IV (both p&amp;lt;0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV→200mg SC group and 50.0% (19/38) in the GUS 400mg IV→200mg SC group achieved clinical response at Wk 24. Clinical response at Wk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV→GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar to Wk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified.

P854 Race and ethnicity in ulcerative colitis clinical trial enrolment: a post hoc analysis of patient demographics and clinical characteristics from GEMINI 1, VARSITY, and VISIBLE 1

Abstract Background The incidence of inflammatory bowel disease (IBD) has risen among Black individuals and Hispanic or Latino individuals in the USA in recent decades; however, these patients are underrepresented in clinical trials of IBD therapies. We aimed to perform a post hoc analysis of the baseline demographics and clinical characteristics in three phase 3 clinical trials of vedolizumab for ulcerative colitis (UC) to identify differences between racial and ethnic groups. Methods The baseline demographics and clinical characteristics of patients with UC who were enrolled in GEMINI 1, VARSITY, and VISIBLE 1 were pooled and stratified by race and ethnicity, which were self-reported. The inclusion criteria for these trials included adult patients with moderately to severely active UC who had a prior inadequate treatment response, loss of response, or intolerance to conventional therapies or anti-tumour necrosis factor α treatment. Data were analysed using descriptive statistics, with mean or median values calculated for continuous variables, and the number and proportion of patients reported for categorical variables. T-tests and exact tests were used to compare continuous and categorical variables, respectively, between Black and White patients and between Hispanic or Latino patients and those who were not Hispanic or Latino. Results We included 1,358 patients, of whom 1,171 (86.2%) were White, 148 (10.9%) were Asian, 14 (1.0%) were Black, and 25 (1.8%) were of multiple or unspecified racial groups (Table 1). Black patients had significantly higher mean weight (87.9 kg vs 74.8 kg, p &amp;lt; 0.01) and body mass index (30.5 kg/m2 vs 25.2 kg/m2, p &amp;lt; 0.01), but lower albumin (38.5 g/L vs 41.2 g/L, p &amp;lt; 0.05) and haemoglobin levels (115.5 g/L vs 126.1 g/L, p &amp;lt; 0.05) than White patients (Table 1). Ethnicity data were recorded for 465 patients (34.2%). Hispanic or Latino patients were shorter in height (166.6 cm vs 171.0 cm, p &amp;lt; 0.01) and had shorter mean disease duration (4.6 years vs 7.6 years, p &amp;lt; 0.01) than those who were not Hispanic or Latino (Table 2). A non-significant, but numerically greater proportion of Hispanic or Latino patients had pancolitis than those who were not Hispanic or Latino (50.0% vs 35.8%). Conclusion In this post hoc analysis of vedolizumab clinical trials, Black patients and Hispanic or Latino patients with UC had differences in certain demographic and disease characteristics versus White patients and patients who were not Hispanic or Latino, respectively. These differences may have implications for therapy. Thus, inclusion of a more diverse patient population that reflects the demographics of the general population is warranted to adequately ascertain drug efficacy across racial and ethnic groups.