Introduction

Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis (UC). Approximately 30% of patients (pts) were clinical nonresponders after 10 wk of OZA treatment in the phase 3 True North (TN) study (NCT02435992), but ~50% of these OZA nonresponders achieved symptomatic response after 5–10 wk of additional OZA treatment during the open-label extension (OLE) study (NCT02531126).

Aims & Methods

This analysis evaluated the impact of TN baseline (BL) endoscopic disease activity on the durability of OZA response in Week (W) 10 OZA clinical nonresponders after extended induction during the OLE up to 4 years (OLE W190). Pts were categorized by BL Mayo endoscopy subscore (MES) as moderate (MES=2) or severe (MES=3). Symptomatic, clinical, and mucosal efficacy were assessed through OLE W190 using observed case (OC) and nonresponder imputation (NRI) analyses.

Results

Of the 226 W10 OZA clinical nonresponders who entered the OLE, 67 had moderate and 159 had severe endoscopic disease at BL. Pt characteristics were generally similar between groups, but more pts with severe vs moderate endoscopic activity had prior immunomodulator (52.8% vs 34.3%), anti–tumor necrosis factor (TNF; 45.9% vs 25.4%), or non–anti-TNF biologic (36.5% vs 19.4%) exposure. Some symptomatic response was observed in OZA W10 clinical nonresponders from BL to W10/OLE entry, which was greater in pts with moderate disease and further improved with extended OZA exposure by OLE W5 (moderate: 36.9% at W10 and 66.2% by OLE W5; severe: 23.8% at W10 and 47.9% by OLE W5). Similar patterns were observed with symptomatic remission but overall rates were lower (moderate: 6.2% at W10 and 26.2% by OLE W5; severe: 1.3% at W10 and 13.0% by OLE W5). Symptomatic response and remission rates after OLE W5 were generally similar in moderate and severe endoscopic activity groups, and rates were maintained throughout the OLE. Likewise, clinical and mucosal efficacy were durable and rates were generally similar between subgroups through OLE W190 (Table). Notably, higher endoscopic improvement rates were achieved through OLE W190 in pts with BL moderate endoscopic activity despite ~50% of these pts progressing to severe by TN W10. Similar data trends were observed in the NRI analysis.

Conclusion

Delayed response to OZA was observed in pts who did not achieve clinical response after 10 wk of OZA therapy, regardless of BL endoscopic activity. W10 nonresponders with moderate endoscopic activity responded faster with additional OZA exposure, whereas those with severe endoscopic activity needed longer exposure to OZA to achieve similar efficacy rates that were durable with continuous OZA exposure. These results suggest that some pts may require a longer induction on OZA but ultimately maintain durable OZA response.

Disclosure

Acknowledgment: This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Traci Stuve, MA, and Julie Ko, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.
PI: received lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts, and Warner Chilcott; received financial support for research from Celltrion, MSD, Pfizer, and Takeda; received advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Hospira, Janssen, MSD, Pfizer, Pharmacosmos, Prometheus Biosciences, Roche, Samsung Bioepis, Sandoz, Takeda, TopiVert, VH2, Vifor, and Warner Chilcott.
RKC: consulted for AbbVie, Bristol Myers Squibb, Fresenius Kabi, Fzata, Janssen, Magellan Health, Option Care, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, Sebela, and Takeda; scientific co-director of the CorEvitas Registry and executive committee member of the IBD Education Group; received financial support for research from Janssen.
TR: served on advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Genentech, Intercept Health, Janssen, Merck, Pfizer, and Takeda; speaker for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda.
AS: declares no competing financial or nonfinancial interests.
PH: consultant and speaker for Boston Scientific, FujiFilm, MedWork, and Viatris.
SC: consultant for AbbVie, Bristol Myers Squibb, Janssen, and Pfizer.
ST, HW, MTO, and AJ: employees and/or shareholders of Bristol Myers Squibb.
DCW: received research funding from AbbVie, Amgen, Arena/Pfizer, Celgene/Bristol Myers Squibb, Genentech, and Janssen; lectured for AbbVie, Bristol Myers Squibb, Janssen, and Takeda; consulted for AbbVie, Arena/Pfizer, Celgene/Bristol Myers Squibb, Eli Lilly, Janssen, and Takeda.

Introduction

Subcutaneous infliximab (IFX-SC) is available in France since February 2021. Beyond pivotal studies enabling marketing authorization, real-world data are needed to assess usage, efficacy and safety of IFX-SC. The aim of RIPOSTE study is to evaluate the real-world use of IFX-SC in France. We present here results from data extracted between 2021 and 2023.

Aims & Methods

This study is based on data from the French administrative health databases (SNDS). All patients with at least one IFX-SC or intravenous (IV) delivery between February 1, 2021 and December 31, 2023, were included, regardless of indication. Diagnoses of Crohn's disease (CD) and ulcerative colitis (UC) were based on published algorithms¹. Four patient groups were defined: (1) IFX-IV incident user (no administration of IFX-IV during look-back period); (2) IFX-IV prevalent user (at least one administration of IV IFX during look-back period); (3) IFX-SC initiation group (patients who received less than 3 infusions of IFX-IV before initiating IFX-SC); (4) IFX-SC switch group (patients who had received at least 3 infusions of IFX-IV before initiating IFX-SC). Patients were followed from the 1^st IFX infusion until IFX discontinuation, initiation of another advanced therapy, death, or December 31, 2023. Discontinuation of infliximab was defined as no new delivery within 3 months of the end of estimated exposure. Persistence of IFX-SC was assessed by the Kaplan-Meier method. Concomitant exposure of immunosuppressant (IS) and the occurrence of serious adverse events were assessed.

Results

A total of 55,230 patients received at least one IFX delivery between February 1, 2021, and December 31, 2023, including 36,778 treated only with IFX-IV and 18,452 with IFX-SC. Among patients treated by IFX-SC, 10,566 (57.3%) had CD, including 2,356 (22.3%) in initiation , and 4,393 (23.8%) had UC, including 1086 (24.7%) in initiation . Switch population involved 8210 CD patients (61.5%) and 33017 UC patients (24.8%). Mean age at cohort entry was 39.82 years (SD, 14.63) in CD and 43.36 years (SD, 15.80) in UC, with 51.14% and 55.03% of women, respectively. IS was combined with initiated IFX-SC in 65.75 % of CD and 59.48% of UC patients. More than 25% of IFX-SC initiated patients did not receive any IFX-IV while 68.2% received 2 IFX-IV infusions. In IFX-SC population, 10.22% of CD and 29.5% of UC patients were concomitantly diagnosed with ankylosing spondylitis (AS). In CD, the 23-month persistence rate was 55% for IFX-IV incident users, while rates were higher in patients treated with IFX-SC, 64% (initiation) and 73% (switch group) (p<0.001). In UC, the 23-month persistence rates were higher in both IFX-SC groups (initiator: 58%; switch: 74%) compared to IFX-IV incident users (44%) (p<0.001) (Table1). Regarding safety, cumulative incidence rate of severe infections at 12 months was numerically higher in IFX-IV group compared to IFX-SC (6% vs 2% in UC; 5% vs 3% in CD).

Table 1: Persistence rate (%) between IFX-SC and IFX-IV for IBD patients

Conclusion

Based on data from the entire French population, IBD patients who switched from IFX-IV to IFX-SC may benefit from a better persistence. Further analyses including propensity score matching to control for residual confounding are ongoing.

References

1. Kirchgesner J, Lemaitre M, Rudnichi A, et al. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014. Aliment Pharmacol Ther 2017;45:37–49.

Disclosure

Funding : Celltrion Healthcare France

Introduction

Ulcerative colitis (UC) is associated with symptoms that may considerably impair patients’ health-related quality of life (HRQoL). Long-term treatment goals established in STRIDE-II include the recuperation of HRQoL in patients with active UC.¹ This post-hoc analysis evaluated the impact of Risankizumab (RZB) as induction and maintenance therapy on normalisation of HRQoL in patients with moderate to severe UC.

Aims & Methods

This study evaluated data from two double-blind, Phase 3 trials, INSPIRE (induction: NCT03398148) and COMMAND (maintenance: NCT03398135). During induction, patients were randomised 2:1 to receive intravenous (IV) RZB 1200 mg or placebo (PBO) at Weeks 0, 4, and 8. Those with a clinical response based on Adapted Mayo score were randomised 1:1:1 to subcutaneous (SC) RZB 180 mg, RZB 360 mg, or PBO (RZB withdrawal) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving normalisation of individual HRQoL outcomes, per literature-based normative value threshold, was assessed at baseline and Weeks 12 and 52: FACIT-Fatigue score; IBDQ score; WPAI-UC (overall work impairment, work time missed, impairment while working, activity impairment); SF-36 PCS; SF-36 MCS; EQ-5D-5L VAS; and EQ-5D-5L index. A composite endpoint was determined to evaluate patients achieving normalisation of all HRQoL outcomes. Adjusted treatment differences between RZB and PBO were analysed using Mantel-Haenszel common rate difference. P values were calculated using Cochran-Mantel-Haenszel test and adjusted for strata.

Results

At Week 12, for RZB 1200 mg IV (n=650) vs PBO (n=325), more patients achieved normalisation of each individual HRQoL outcome (p<=0.01) (Table 1). For RZB SC 180 mg (n=179) and 360 mg (n=186), more patients achieved normalisation of FACIT-fatigue, IBDQ, and SF-36 PCS vs PBO at Week 52 (p<=0.05). More patients also achieved normalisation of all WPAI-UC scores with RZB 180 mg SC vs PBO (p<=0.05), excluding overall work impairment. For SF-36 MCS and both EQ-5D-5L scores, more patients achieved normalisation with RZB 180 mg SC vs PBO (p<=0.05), but not with RZB 360 mg SC. Normalisation of the composite HRQoL score was achieved by more patients with all doses of RZB vs PBO at Weeks 12 (RZB 1200 mg: 12.5%; PBO: 4.9%) and 52 (RZB 360 mg: 20.4%; RZB 180 mg: 21.2%; PBO: 10.9%) (p<=0.05).
Table 1. Proportion of patients with UC achieving normalisation of HRQoL outcomes after treatment

Conclusion

RZB shows greater normalisation of HRQoL compared to PBO, with results seen early during induction and subsequently continued through maintenance. These results indicate that the long-term treatment goal of HRQoL normalisation in patients with moderately to severely active UC may be achievable with RZB.

References

1. Turner D, et al. Gastroenterology. 2021;160:1570–83.

Disclosure

Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.
Parambir Dulai received research support and/or consulting for AbbVie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genetench/Roche, Geneoscopy, Janssen, Pfizer, Takeda.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.
Satoshi Tanida received speaker fees from Kissei, Mitsubishi Tanabe Pharma, Jimro, AbbVie, and Janssen.
Irina Blumenstein has received consultancy honoraria from AbbVie Deutschland, Amgen GmbH, Bristol Myers Squibb, Janssen Cilag GmbH, Fresenius Kabi Deutschland, Pharmacosmos GmbH, Pfizer GmbH, Shire Deutschland GmbH, and Takeda Pharma GmbH; and received honoraria from AbbVie Deutschland, Biogen GmbH, DGVS, Dr. Falk Pharma GmbH, Endoakademie, Ferring Arzneimittel, Fraunhofer, Fresenius Kabi Deutschland, Kompetenznetz Darmerkrankungen, MSD Sharp Dome, Mylan GmbH, Pfizer GmbH, Janssen Cilag GmbH, Shire Deutschland GmbH, and Takeda Pharma GmbH.
Remo Panaccione has received consulting fees, speaker fees, research/educational support from, and/or advisory board member for AbbVie, Abbott, Alimentiv (formerly Robarts), Amgen, Arena, AZ, BI, BMS, Celgene, Celltrion, Cosmos, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead, GSK, Janssen, Lilly, Merck, Mylan, Oppilan, Pandion, Pfizer, Progenity, Protagonist, Roche, Satisfai, Sandoz, Schering-Plough, Shire, Sublimity, Theravance, Takeda, and UCB.
Yuri Sanchez Gonzalez, Dolly Sharma, Nidhi Shukla, Valencia Remple, Jasmina Kalabic, and Patrick M Hechtare full-time employees of AbbVie and may hold AbbVie stock and/or stock options.
Funding statement: Financial support for the study was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content. No honoraria or payments were made for authorship. Medical writing services provided by Kay Hallam, MSc, of Fishawack Facilitate, Ltd, part of Avalere Health and funded by AbbVie.