Introduction

We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naïve and bio-exposed ulcerative colitis (UC) patients in a real-world setting.

Aims & Methods

Retrospective, Canadian multicenter cohort study. Standardized data collection was performed on consecutive adult UC outpatients treated with ustekinumab in 4 large IBD centers. The primary outcomes were clinical remission and endoscopic remission. Key secondary outcomes included composite clinical and endoscopic response, safety, and persistence. A multivariable Cox proportional hazards model was used to explore associations between baseline factors and endpoints. For multivariable model selection, backwards elimination was used with a threshold P < 0.05.

Results

A total of 198 patients were included, of whom 47.5% were female and 85.9% under 65 years. The majority had severe endoscopic activity at baseline (47.5%, n=87) and were bio-exposed (88.8%, n=176; 33%, n=66 prior failure of 3 or more biologics. Patients were followed for a median of 12.8 (IQR 8.2 to 22.1) months after induction. Clinical remission rates were 43.7% (69/198), 43.8% (56/128), and 62.4% (58/93) at 3, 6 and 12 months respectively. Endoscopic remission rates were 11.3% (7/62), 24.7% (23/93), and 23.4% (11/43) at 3, 6 and 12 months respectively. Bio-naive patients were more likely to achieve clinical and endoscopic remission compared to bio-exposed (HR=1.71, 95% CI: 1.02–2.88, and HR=7.33, 95% CI: 2.15–25.01, respectively). Adverse events were reported in 14.1% (18/198), with colectomies exclusively observed in bio-exposed individuals (8.6%; 17/198).

Conclusion

In a highly refractory and largely bio exposed population more than half of patients with UC treated with ustekinumab achieved clinical remission and one-third achieved endoscopic remission. Prior biologic exposure was independently associated with clinical and endoscopic remission. Safety profile was consistent with interleukin (IL)-12-23 blockade.

Disclosure

VS, AN, KES, AZ, LG have no conflict of interest
NN has been a speaker or advisor for Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Fresenius Kabi, Innomar, Iterative Scopes, Bristol Myers Squibb, Viatris and Ferring
TB has received consulting or speaker fees for Abbvie, Alimentiv, Amgen, Bristol Myers Squibb, Ferring, Janssen, Merck, Pfizer, Roche, Sandoz, Takeda, Gilead, Viatris, Fresenius, Kabi
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Ferring, Janssen, Takeda, and Pfizer; research support from Ferring, Pfizer
VJ consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.

Introduction

Ustekinumab, an interleukin (IL) 12/23 inhibitor is a biologic used to treat inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Clinical and real-world evidence has demonstrated its ability to provide a clinically meaningful response and remission among patients; however, the economic impact of its use may not be favourable from the payer perspective. The objective of this targeted literature review was to understand the economic impact of ustekinumab reference product in the treatment of patients with IBD.

Aims & Methods

A literature search was conducted in MEDLINE for economic publications that evaluate the economic impact of ustekinumab or include ustekinumab within their analyses. Search terms included “budget impact model”, “budget impact analysis”, “cost-utility”, “cost-effect”, “ulcerative colitis”, “Crohn’s disease” and “ustekinumab” from database inception until Feb 8^th, 2024. Only studies published in English were eligible for inclusion.

Results

A total of 30 hits were screened for inclusion, yielding 12 relevant studies that discussed economic implications of ustekinumab. Five articles were conducted from the US payer perspective, two from the Japanese payer perspective, and one each from the Canadian, Swedish, Polish, French, and German perspectives. The economic models included budget impact models (n = 2), cost-effectiveness models (n = 8), and cost per responder/remitter analyses (n = 2). Five studies used a CD patient population, six studies focused on UC, and one study included a mixed population of CD and UC. In CD studies, two found ustekinumab was cost-effective: these studies were conducted from the perspective of Polish and Swedish payers in CD patients who failed anti-TNF therapy. Both studies used a Markov based model to assess cost-effectiveness of treatments. In the remaining CD studies, ustekinumab was associated with the highest cost per responder/remitter (Japanese payer perspective) and was dominated by other treatments in cost-effectiveness analyses (US payer perspective). The studies conducted in the UC patient population also found that, although clinically effective, ustekinumab was dominated (based on the incremental cost effectiveness ratio [ICER]) by other biologics included in the analyses (eg, vedolizumab and infliximab). Similar to the CD patient population, the cost per responder/remitter was highest for ustekinumab compared to five other therapies including tofacitinib and golimumab (US payer perspective). However, in two UC studies, ustekinumab was observed to be more effective than the most cost-effective treatment option (from the Japanese and US payer perspectives), highlighting that its price negatively affected its ICER. Moreover, cost-effectiveness analyses conducted by the German and Canadian perspectives, demonstrated that ustekinumab was not a cost-effective therapy at the current willingness to pay threshold (0% probability). Note, that no studies tested the possible cost-effectiveness of an ustekinumab biosimilar which would positively influence the cost associated with ustekinumab treatment.

Conclusion

This literature review demonstrated that, despite its high efficacy, ustekinumab is among the highest costing biologics available for the treatment of IBD with low probabilities of cost-effectiveness across several studies. As the economic burden for IBD is increasing globally, cost-saving therapeutic options such as biosimilars may help to provide savings that can be redistributed in a healthcare system or provide funds to expand patient access.

Disclosure

Kunal Shastri is an employee of Fresenius Kabi a manufacturer of biosimilars. Kerise Clarke, Margaret Ainslie-Garcia, Nicole Ferko are employees of EVERSANA a company who receives consulting fees from Fresenius Kabi.

Introduction

Histologic inflammation persists in up to one quarter of patients with Crohn’s Disease (CD) despite endoscopic mucosal healing. Responsiveness of histologic inflammation to treatment is an evolving outcome measure in CD. Mirikizumab (MIRI) increased histologic response (H-Res) and remission (H-Rem) relative to placebo (PBO) in the Phase 2 SERENITY trial.¹

Aims & Methods

We compared the effect of MIRI on H-Res and H-Rem at week (W)12 and W52 to PBO by composite endpoints of response (clinical response by Patient-Reported Outcome [PRO] at W12 and W52 H-Res) and of remission (clinical response by PRO at W12 and W52 H-Rem) at W52. The overall population of patients with moderately to severely active CD, patients without prior biologic failure (non-BF), and patients with prior BF were assessed, using data from the Phase 3 VIVID-1 trial (NCT03926130). Two biopsy specimens from each of 5 intestinal segments (1 ileal and 4 colonic) were obtained from the edge of the ulcers, or the most inflamed mucosa from randomized patients at screening, W12, and W52. Criteria for H-Res were the absence of epithelial neutrophils and epithelial damage, erosions, and ulceration or ≥50% decrease in either the sum of the 5 segments of Robarts Histopathology Index or the Global Histologic Disease Activity Score. H-Rem was defined as complete absence of mucosal neutrophils (in epithelium and lamina propria), and no epithelial damage, erosions, and ulcers; these criteria had to be met in all biopsy specimens. Clinical response by PRO was defined as ≥30% decrease in stool frequency and/or abdominal pain with neither score worse than baseline. H-Res, H-Rem, composite H-Res, and composite H-Rem in all patients were prespecified, non-multiplicity-controlled endpoints. Analyses in non-BF and BF patients were post hoc.

Results

At W12, treatment with MIRI resulted in nominally statistically significantly higher rates of H-Res in all three patient groups analyzed (p<.001) (Table). At W12, differences between MIRI vs PBO were nominally significant in achieving H-Rem in all patients (p<.01) and in non-BF and BF patients (both p<.05). For W52 composite H-Res, differences between MIRI vs PBO were nominally statistically significant in all patient groups examined (p<.001). For W52 composite H-Rem, nominally statistically significant differences between MIRI vs PBO were observed in all patients (p<.001), in non-BF patients (p<.05), and in BF patients (p<.001).

Conclusion

Based upon strict definitions that applied to all 5 intestinal segments, MIRI achieved nominally significantly higher rates of H-Res and H-Rem compared to PBO in all patients at W12 and W52. The statistical difference was more pronounced in the BF population after 1 year of treatment.

References

1. Magro F, et al. Clin Gastroenterol Hepatol. 2023;S1542-3565(23)00948-5.

Disclosure

V. Jairath received fees or grant and/or research support and/or served as a consultant and/or speaker for: AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Metacrine, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx Biosciences, Vividion Therapeutics; F. Magro served as a speaker for: AbbVie, Arena, Biogen, Bristol Myers Squibb, Eli Lilly and Company, Falk, Ferring Pharmaceuticals, Hospira, Janssen, Laboratórios Vitoria, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, UCB, Vifor; G De Hertogh received fees for clinical trial activities with Centocor Inc; and received consultancy fees from: Eli Lilly and Company, MRM Health; B. Feagan was a consultant for: AbbVie, AbolerIS Pharma, Agomab Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport, Arena Pharmaceuticals, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celgene/BMS, Celsius Therapeutics, Connect BioPharma, Cytoki Pharma, Disc Medicine, Duality, EcoR1, Eli Lilly and Company, Equillium, Ermium Therapeutics, First Wave BioPharma, First Word Group, Galapagos NV, Galen Atlantica, Genentech/Roche, Gilead Sciences, Gossamer Pharma, GlaxoSmithKline, Hinge Bio, Hot Spot Therapeutics, InDex Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco, Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium Pharmaceuticals, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist Therapeutics, PTM Therapeutics, Q32 Bio, Rebiotix, Redx Pharma, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHsquared, Viatris, Ysios, YSOPIA Bioscience, and Zealand Pharma; was on the speaker’s bureau for: AbbVie, Janssen, and Takeda; a member of the Scientific Advisory Board, DSMB for: AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer Ingelheim, Celgene/BMS, Ecor1Capital, Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, InDex Pharma, Janssen, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, Redx Pharma, Sanofi, Takeda, Tillotts Pharma, and Teva; a stock shareholder of: Gossamer Pharma; and an employee as Senior Scientific Director of: Western University and Alimentiv; N. Harpaz served as an advisory board member and/or consultant for: AbbVie, Bristol Meyers Squibb, Eli Lilly and Company, PathAI Inc; T. Hisamatsu received lecture fees from: AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceutical K.K., JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda; has received honoraria as an advisory board member or consultant for: AbbVie, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Pfizer, Takeda; and has received pharmaceutical/research grants from: AbbVie, Alfresa Pharma, Daiichi Sankyo, EA Pharma, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nichi-lko Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Zeria Pharmaceutical; G. D’Haens has been an advisor for: AbbVie, AgomAb Therapeutics, AstraZeneca, Avaxia Biologics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Eli Lilly and Company, Exeliom Biosciences, Galapagos NV, GlaxoSmithKline, Immunic Therapeutics, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, ProciseDx, ProDigest, Progenity, Samsung Bioepis, Sanofi, Takeda, Tillotts Pharma AG, Ventyx; and received speaker’s fees from: AbbVie, Johnson & Johnson, Takeda, Pfizer, Tillotts Pharma AG; R. Pai received consulting fees from: Alimentiv Inc, Allergan, BRACCO. Z. Lin, N. Morris, M. Protic, E. Hon, C. Owen, and R. Escobar are employees and shareholders of: Eli Lilly and Company; W. Reinisch received lecture and consulting fees from and/or served as an advisory board member for: AbbVie, Actelion, Alpha Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Genentech, Grunenthal, Johnson & Johnson, Millennium, Merck, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, Salix Pharmaceuticals, Takeda, UCB Pharma, Vifor Pharma.

Introduction

Mirikizumab was approved for the treatment of Ulcerative colitis (UC) in May 2023. However, real-world data especially in biological-experienced patients, is scarce.

Aims & Methods

We aimed to determine treatment efficacy and persistence on Mirikizumab in mostly treatment-experienced UC patients.
All patients, who were treated for UC in the inflammatory bowel disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-03/23 were retrospectively analyzed. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)) as well as patient history were collected. Patients were followed-up for at least 12 weeks.

Results

Twenty-one patients with UC were included. Eighteen patients had already received at least one biological agent prior to starting Mirikizumab. Thirteen patients were exposed to ≥ 2 biological agents and even 6 patients to ≥ 4 biological agents prior to starting Mirikizumab. Two patients received Mirikizumab as a first line treatment. Eight patients were treated with Ustekinumab prior to the therapy with Mirikizumab. Ten patients received oral steroids as concomitant treatment. The median SCCAI at the start of induction was 7 (1-18). We report a reduction in clinical disease activity to 2 (0-11) at week 12 based on the preliminary data of the SCCAI. Median SCCAI and FC levels are shown in table 1.
Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 642 (14-2100). At week 12 the median FC level was 253 (21-2100) and 330 (9-2100) at week 12. Intravenous induction therapy was extended in 11 patients, with 10 patients receiving 6 infusions. Four patients were re-induced after having previously received Mirikizumab subcutaneously. One patient discontinued treatment after an extended induction due to a primary non-response. One patient reported new nodulous skin lesions after the treatment with Mirikizumab.

Conclusion

We report preliminary real-world data on the treatment with Mirikizumab. In our interim analysis Mirikizumab proves to be an effective and safe treatment in biological-experienced UC patients.

Disclosure

AK reports consulting and lecturer fees and travel grants from Takeda, Janssen-Cilag, Celgene/BMS GmBH, AbbVie, Falk Foundation and Galapagos, RL reports consulting and lecturer fees and travel grants from AbbVie, Janssen-Cilag , KF reports consulting and lecturer fees from Vifor Pharma, Immundiagnostik AG, MSD/Merck, Takeda, BMS GmbH Pharmacosmos, AbbVie, Celgene/BMS, SZ reports consultancy and speaker’s bureau fees from AbbVie, Allergan, Biomarin, Gilead, Intercept, Janssen-Cilag, MSD/Merck, Novo Nordisk, SoBi and Theratechnologies and IB reports consulting and lecturer fees from Takeda, AbbVie, Amgen, Biogen, Janssen-Cilag, Celgene/BMS GmBH, Celltrion, Falk Foundation, Fresenius Kabi, Galapagos, Lilly, Pharmacosmos and Pfizer, KS reports consulting fees and clinical studies from Abbvie, BMS, Cymabay, Chemomab, Calliditas, Falk, Ipsen, Jannsen-Cilag, Gilead, GDK, MSD, Roche, VIR, MSD, AD none

Introduction

Symptomatic, endoscopic, and histological remission simultaneously, known as disease clearance (DC), has been proposed as an aspirational target in ulcerative colitis (UC). [1, 2] Mirikizumab (miri), an anti-IL-23p19 antibody, has demonstrated strong efficacy as shown by single and combined clinical endpoints in LUCENT Phase 3 trials. [3-5] This analysis evaluated the impact of miri on DC during LUCENT-1 (NCT03518086), LUCENT-2 (NCT03524092) and long-term LUCENT-3 (NCT03519945) trials and the association between DC and other clinical and patient-reported outcomes (PROs).

Aims & Methods

DC is defined as symptomatic remission [Mayo stool frequency (SF)=0, 1 with a ≥1 point decrease from baseline + rectal bleeding (RB)=0], and histologic-endoscopic mucosal remission [HEMR: Mayo endoscopic remission (ER: endoscopy subscore of 0 or 1, excluding friability) + Geboes score ≤2B.0]. PROs of interest included Fatigue NRS, IBDQ remission, SF-36, WPAI:UC, PGRS, and PGRC (see table footer). Clinical outcomes include clinical remission, corticosteroid-free remission, ER, HEMR, bowel urgency (BU) remission, SF remission, and RB remission. [2,5] The proportion of patients achieving DC was assessed at W12, W52, and W104. Treatment comparisons were made using a CMH test adjusting for randomization factors. Associations between the PROs and DC were evaluated at W12 and W52 in miri-treated patients. The associations between clinical outcomes and early achievement of DC in miri-treated patients at W12 and W52 were evaluated at W52 and W104, respectively. Non-responder imputation was used for all analyses.

Results

A significantly higher proportion of miri-treated patients achieved DC vs PBO at W12 [N=868 miri, 294 PBO] (DC: 16.0% vs 7.1%, p<0.0001) and W52 [N=365 miri, 179 PBO] (DC: 36.4% vs 19.6%, p=0.0002). Similar trends were seen for biologic failure subgroups at W12 (bio/JAKi-failed: [n=361 miri, 118 PBO; DC: 9.1% vs 5.9%]; bio&JAKi-naïve: [n=492 miri, 171 PBO; DC: 20.9% vs 7.6%]) and W52 (bio/JAKi-failed: [n=128 miri, 64 PBO; DC: 31.3% vs 12.5%]; bio&JAKi-naïve: [n=229 miri, 114 PBO; DC: 39.3% vs 23.7%]). At W104 (N=239 miri), 40.6% of patients achieved DC with 2-year treatment with miri. Specifically, 38.4% of bio/JAKi-failed (n=73) and 40.9% of bio&JAKi-naïve (n=159) patients achieved DC. Significantly greater improvement in all PROs was seen at W12 for patients who achieved DC vs those who did not at W12 in miri-treated patients. Similar associations were observed at W52, except in WPAI:UC overall work productivity (Table 1A). Patients achieving DC at W12 were more likely to achieve all clinical outcomes, except BU remission, at W52 versus those who did not achieve DC at W12. This trend was repeated in patients who achieved DC at W52 and continued to W104 (Table 1B).

Conclusion

Miri consistently demonstrated DC across induction, maintenance, and long-term studies. Over 36% of patients achieved DC after one year of miri treatment. The attainment of DC was associated with improvement in PROs in LUCENT-1 and -2. Early achievement of DC was associated with better long-term clinical outcomes.

References

1. D’Amico, F., et al., Disease Clearance as a New Outcome in Ulcerative Colitis: a Systematic Review and Expert Consensus. Inflammatory Bowel Diseases, 2023.
2. Ramos, L., J. Teo-Loy, and M. Barreiro-de Acosta, Disease clearance in ulcerative colitis: Setting the therapeutic goals for future in the treatment of ulcerative colitis. Front Med (Lausanne), 2022. 9: p. 1102420.
3. D'Haens, G., et al., Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med, 2023. 388(26): p. 2444-2455.
4. Sands, B.E., et al., Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study. Inflamm Bowel Dis, 2024.
5. Magro, F., et al., Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. Journal of Crohn's and Colitis, 2023. 17(9): p. 1457-1470.

Disclosure

J-F. Colombel reports research grants from AbbVie, Janssen, and Takeda; payment for lectures from AbbVie, Allergan, Amgen, Ferring, Shire, and Takeda; consulting fees from AbbVie, Amgen, Anaptys Bio, Arena, BMS, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galmed, Genentech, GlaxoSmithKline, Janssen, Kaleido, Imedex, Immunic, Iterative Scopes, Landos, Merck, Microba, Novartis, Otsuka Pharmaceutical, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, and Vifor; and holds stock options in Intestinal Biotech Development.
T. Kobayashi served as an advisory board member, consultant, or speaker for AbbVie, Activaid, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda and Zeria Pharmaceutical and has received research funding from AbbVie, Alfresa Pharma, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda and Zeria Pharmaceutical. research grants from Abbvie GK, Activaid, Alfresa Pharma Corporation, Bristol-Myers Squibb Eli Lilly Ferring Pharmaceuticals Japan K.K., Gilead Sciences, Inc., JMDC Inc., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., received scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co., Ltd Zeria Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., and belonged to study group sponsorship by Alfresa Pharma Corporation, JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd. ZeriaPharmaceutical Co., Ltd. And received advisory/consultancy fees from Abbie GK, Activaid, Celltrion Healthcare, EA Pharma Co., Ltd., Eli Lilly, Ferring Pharmaceuticals Japan K.K., Gilead Sciences, Janssen Pharmaceutical K.K., KISSEI Pharmaceutical Co., Ltd, itsubishi Tanabe Pharma Corporation, Pfizer Japan Inc, Takeda Pharmaceutical Co., Ltd.
J. Wu, B. Zhu, I. Redondo, and R. Moses are employees of Eli Lilly.
V. Jairath reports consulting / advisory board for AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker for AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
C. Siegel reports consulting for AbbVie Inc, Bristol Myers Squibb, Fresnius Kabi, Eli Lilly and Company, Janssen Pharmaceuticals, Napo Pharmaceuticals Inc, Pfizer Inc, ProciseDx, Prometheus, Takeda Pharmaceutical Company, and Trellus Health Inc; being a speaker for continuing medical education activities for AbbVie Inc, Janssen Pharmaceuticals, Pfizer Inc, and Takeda Pharmaceutical Company; and receiving grant support from AbbVie Inc, Janssen Pharmaceuticals, Pfizer Inc, and Takeda Pharmaceutical Company.
B. Siegmund received research grants from Pfizer and Arena; consulting fees from AbbVie, Abivax, Arena, Bristol Myers Squibb, Boehringer, CED Service, Celgene, CT Scout, Endpoint Health, Falk, Forga Software, Galapagos, Janssen, Lilly, Materia Prima, Pfizer, Takeda, Pharma Insight, Predictimmune, and PsiCro; speaker honoraria from AbbVie, Bristol Myers Squibb, CED Service, Chiesi, Falk, Ferring, Gilead, Janssen, Lilly, Materia Prima, Takeda, and Pfizer; and is President of the European Crohn's and Colitis Organisation.
F. Magro has served as a speaker and received honoraria from: AbbVie, Biogen, Falk, Ferring, Hospira, Laboratórios Vitória, Merck Sharp & Dohme, and Vifor.

Clinical Case Summary

A 22-year-old female without comorbidities presented with epigastric and lower retroesternal chest pain, nausea and vomiting since 3 days that didn't response to oral medication. Patient denied dysphagia or odinophagia. Assessed in the emergency, treated with intravenous (IV) medications and discharged with prescription. Next day, the pain increased and vomited 15 times. Patient was admitted as a case of acute gastritis on intravenous proton pump inhibitors (PPIs) and metoclopramide. Routine laboratory and upper abdominal ultrasound done without significant findings only remarkable mild hyponatremia 134 (135-145).
Physical examination looked unwell. Vitally stable 105/75 mmHg. Afebrile (36.2). Malnourished. Weight 28.7 Height 145cms BMI 14.2. Mild epigastric tenderness.
Due to refractory symptoms despite IV medication. Endoscopy was done and showed round and serpiginous ulcers in the lower third of the esophagus with yellowish exudate suggestive of infectious esophagitis Cytomegalovirus vs Herpes. Normal aspect of stomach and duodenum. Histopathology confirmed herpes simplex esophagitis.
Under the suspicion of infectious esophagitis HIV serology came negative, CMV antibodies IgM negative IgG positive. Normal immunoelectrophoresis. No previous herpes viral infection. The only risk factor identified for the patient was the malnutrition, nevertheless vitamins and proteins were normal.
With histological confirmation after 48 hours of the endoscopy she was started on Acyclovir IV 5mg/kg every 8 hours with significant improvement in the next 48 hours. Patient discharged in stable condition after re-starting oral intake and completing the oral acyclovir 400 mg every 8 hours for 10 days. Patient responded well was assessed 7 days after discharge, free of symptoms and a weight gain of 1.3 kg.
Infectious esophagitis needs to be considered in immunocompetent host. Odynophagia/dysphagia can be absent. Endoscopy findings alone isn't sufficient to make a definitive diagnosis.

References

Endoscopy and histopathology.

Introduction

Inflammatory bowel disease (IBD) is a chronic autoinflammatory disease with no known cure, characterized by chronic inflammation and ulcers in the gastrointestinal tract.[1] IBD has historically been observed in industrialized societies and is now on the rise in regions undergoing rapid industrialization.[2] Measuring and describing IBD trends are crucial due to the high disease burden, healthcare costs, and impact on quality of life. Accurate descriptions of disease patterns can inform research and public health agendas, and improve healthcare preparedness worldwide.

Aims & Methods

This report focuses on the temporal and geographical trends of IBD in terms of incidence and prevalence. Prevalence and incidence data of ulcerative colitis (UC) and Crohn’s disease (CD) are extracted from population-based studies identified through a series of systematic literature reviews. A total of 92 sources of prevalence and 174 sources of incidence were identified. We analyzed all data using DisMod-MR 2.1, a Bayesian meta-regression tool to estimate both prevalence and incidence.[3] We also conducted a decomposition analysis to evaluate the impact of population growth and aging in the prevalence changes between 1990 and 2021.

Results

In 2021, 3.84 million (95% Uncertainty level 3.29 to 4.43) people were estimated to be living with IBD globally. Of these, 1.43 million (1.16 to 1.73) were living with CD and 2.41 million (2.02 to 2.95) with UC. The global all-age prevalence of CD, UC, and IBD in 2021 were 18.1 (14.6 to 21.8), and 30.5 (25.5 to 37.3), 48.6 (41.6 to 55.9) per 100,000, respectively. The global all-age incidence of IBD increased from 3.7 (3.3 to 4.4) per 100,000 in 1990 to 4.8 (4.2 to 5.6) per 100,000 In 2021. The incidence of IBD has shown a slight increase in high-income super-region, resulting in a relatively small rise in prevalence in this region. The all-age IBD incidence rate in high-income super-region increased by 23.2% from 12.5 (11.1 to 14.3) per 100,000 in 1990 to 15.4 (13.8 to 17.4) per 100,000 in 2021, and the all-age prevalence rate in this region also increased by 25.5% from 157 (139 to 175) per 100,000 in 1990 to 197 (171 to 221) per 100,000 in 2021. In contrast, our study found that low-income regions, such as Southeast Asia, East Asia, and Oceania, experienced a much larger increase in the incidence and prevalence rates of IBD over the same period. The all-age IBD incidence rate in this region rapidly increased by 118.3% from 0.646 (0.546 to 0.783) per 100,000 to 1.41 (1.23 to 1.69) per 100,000, and the all-age IBD prevalence rate more than doubled from 5.32 (4.54 to 6.32) per 100,000 to 11.8 (9.8 to 14.0) per 100,000.

Conclusion

Overall, IBD is becoming more prevalent globally. Although incidence and prevalence of IBD in high-income countries have been relatively stable, with rising mean estimates but overlapping 95% uncertainty intervals, many lower-income countries have experienced a notable rise in both measures. This larger increase may be attributable to changes in lifestyle and diet associated with industrialization and urbanization. Population growth in low-income countries, such as sub-Saharan Africa, played a significant role in driving the increase in prevalent IBD cases, while population aging was the dominant factor in high-income countries, particularly in Europe. These findings highlight the complex interplay between socio-demographic factors and IBD prevalence and emphasize the need for tailored interventions in different regions based on their unique characteristics.

References

1. Meenakshi Bewtra, Chinyu Su, and James D. Lewis, “Trends in Hospitalization Rates for Inflammatory Bowel Disease in the United States,” Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association 5, no. 5 (May 2007): 597–601, https://doi.org/10.1016/j.cgh.2007.01.015.
2. Gilaad G. Kaplan and Siew C. Ng, “Globalisation of Inflammatory Bowel Disease: Perspectives from the Evolution of Inflammatory Bowel Disease in the UK and China,” The Lancet. Gastroenterology & Hepatology 1, no. 4 (December 2016): 307–16, https://doi.org/10.1016/S2468-1253(16)30077-2.
3. Theo Vos et al., “Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019,” The Lancet 396, no. 10258 (October 2020): 1204–22, https://doi.org/10.1016/S0140-6736(20)30925-9.