Tag Archives: Ulcerative colitis

Understanding the Economic Burden of Inflammatory Bowel Disease

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J Burisch et al. Clin Gastroenterol Hepatol 2025; 23: 386-395. Open Access! The Cost of Inflammatory Bowel Disease Care: How to Make it Sustainable

This article is a terrific review of care cost drivers in inflammatory bowel disease (IBD) but it does not actually have useful information on how to make the costs of care sustainable.

Key points:

  • The most recent data from the United States (U.S.) estimated that the prevalence of IBD
    was 0.7% of the population, representing 2.39 million individuals living with IBD…the annual cost of IBD in the U.S. approximates $50 billion
  • All studies demonstrated a shift over time from costs associated with hospitalizations to costs of medications
  • The costs of prescription drugs for IBD vary significantly worldwide… A particular outlier among high-income countries is the U.S., where manufacturers set prices freely. The lack of
    nationwide price regulation, coupled with the fragmentation of the U.S. health care system and prolonged market exclusivity periods, result in U.S. drug prices that exceed, on average, international prices by several-fold…Even when insurers are successful at negotiating discounts, patients seldom benefit, as costsharing paid at the point-of-sale is based on the full, non-discounted price
  • Using a “top-down” clinical paradigm, guidelines suggest starting biologic medications early to induce remission of moderate-to-severe IBD, thereby reducing risk of complications, surgeries, and hospitalizations and improving quality of life.55,58 A randomized controlled
    trial demonstrated a clear benefit in steroid-free and surgery-free remission among patients randomized to top-down vs step-up care (79% vs 15%; P < .0001) [PROFILE study]

In terms of improving cost sustainability, here is what the authors propose “Strategies for cost reduction in the clinical treatment of IBD”:

My take: This article highlights the cost drivers in IBD but does not identify a path that appears to help address affordability.

This article is one of 11 articles in special issue discussing the future of IBD care.

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Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization

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JD Lewis et al. Clinical Gastroenterology and Hepatology. 2024; Volume 22, Issue 12, 2475 – 2486.e14. Open Access ! Provider Specialization in Inflammatory Bowel Diseases: Quality of Care and Outcomes

Methods:  This was a retrospective cohort of newly diagnosed patients with IBD using data from Optum’s deidentified Clinformatics Data Mart Database (2000–2020). The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers.

Key findings:

  • In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn’s disease (P < .05 for all comparisons)
  • In children, none of the associations between provider focus and process or outcome measures were significant. Although not statistically significant among children, the OR for mesalamine use was 0.64, suggesting a similar association as that seen among adults
Time to first dispensing of a biologic therapy in (A) children and (B) adults

My take: This study indicates significant treatment disparities between IBD-focused care providers and providers without an IBD focus in the care for adults, but not in the care of children. This could be related to improved collaboration among pediatric care providers, better training, and parental involvement.

In addition, this study focused on patients with newly-diagnosed disease. Treatment is more complicated in patients who have not responded to initial treatments; as such, IBD-focused providers may be more important in this population.

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Comparing Infliximab, Adalimumab, and Vedolizumab in Adults and Children with Ulcerative Colitis

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O Atia et al. Infammatory Bowel Diseases, 2025, 31, 617–624. Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN

This was a nationwide Israeli study with 15,111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years. The dataset includes ~98% of the Israeli population; “the accuracy of medication data is high, as the Israeli health care system provides medications almost free of charge through the HMOs, and the electronic dispensing of drugs contributes to reliable and precise data.”

Key findings:

  • After 5 years of treatment, 43% of the patients with UC sustained their first biologic
  • The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively)
  • Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively) or combotherapy (78%/56% vs 91%/58%, respectively)
  • Durability of infliximab at 1 yr and 5 yrs was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; , P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%)
  • The durability rate was similar for vedolizumab monotherapy at 1 yr and 5 yrs (77%/56%) compared with adalimumab monotherapy (69%/52%), and infliximab monotherapy (73%/55% vs 62%/44%). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%), respectively;

My take: When looking at the durability plots, the three main biologics in this study, infliximab, adalimumab and vedolizumab, performed similarly. Whether therapeutic drug monitoring would influence theses results is not clear. It is interesting that a recent study in the pediatric population found that combination therapy was important for adalimumab and not infliximab (see: Why Do Children Taking Adalimumab Benefit from Methotrexate Dual Therapy?)

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Also, from AGA Today (3/20/25): FDA Approves Guselkumab To Treat Patients With Crohn’s Disease

HCPlive (3/20, Campbell) reports the FDA on Thursday announced the approval of “guselkumab (Tremfya) for the treatment of adults with moderately to severely active Crohn disease.” The announcement from Johnson and Johnson claims the “approval is based on data from multiple phase 3 trials, including the GALAXI trials, which found guselkumab outperformed ustekinumab (Stelara) for multiple endoscopic endpoints. The agent now boasts indications for moderately to severely active Crohn disease and moderately to severely active ulcerative colitis (UC).” This is the fourth indication for guselkumab in the US

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

HLA-DRB1*01:03: Biomarker for Severe Ulcerative Colitis

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MV Vestergaard et al. . JAMA. Published online October 15, 2024. doi:10.1001/jama.2024.20429. HLA-DRB1*01:03 and Severe Ulcerative
Colitis

Background: This study aimed to identify biomarkers by conducting a Danish nationwide genome-wide association study (GWAS) on severe vs less severe ulcerative colitis.

Methods: Severe ulcerative colitis: Patients with severe ulcerative colitis were defined as having at least 1 major ulcerative colitis–related operation, at least 2 ulcerative colitis–related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis

The authors utilized two source populations

  1. The Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) neonatal blood spot cohort (NBS) includes individuals born in Denmark and diagnosed with ulcerative colitis from 1981 to 2022
  2. The North Denmark Biobank study is a population-based cohort of patients from Northern Denmark with inflammatory bowel disease from 1978 to 2020 (NorDIBD)

The combined cohort included 4491 patients (4153 from NBS and 338 from NorDIBD) with a mean (SD) age at diagnosis of 23.3 (8.4) years; 53% of patients were female and 27% had severe disease.

Key findings:

  • The association with HLA-DRB1*01:03 (Figure 1) had an OR of 6.38 for major operation, OR of 5.24 for at least 2 hospitalizations, and OR of 2.30 for use of at least 5000 mg
    of systemic corticosteroids in carriers vs noncarriers
  • Carriage of HLA-DRB1*01:03 allele was 2.8% in these cohorts
  • Limiation: Danish cohort -may not be applicable to other populations

My take: HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Antibiotics and IBD Risk: A Systematic Review

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R Duan et al. Clin Gastroenterol Hepatol 2025; 23: 45-58. Open Access! Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis

Twenty-eight studies involving 153,027 patients with IBD were included.

Key findings:

  • Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29–1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08–1.68). ‘
  • This association existed for both Crohn’s disease and ulcerative colitis, as well as in children and adults for prescription-based studies. 

Some of the limitations:

  1. There was statistical heterogeneity was high in the primary analysis, possibly because of inconsistencies in study design
  2. Most studies included a clear lag time, yet an inadequate lag time still creates the possibility of reverse causality.
  3. The authors could not disentangle the risk of antibiotics from the risk of infection in leading to the development of IBD.
Nonlinear dose-response relationship between antibiotic exposure and risk of new-onset IBD (solid black line and short dash black line represent estimated ORs and corresponding 95% CIs of nonlinear relationship)

My take: This is another study showing an association between antibiotic use and new-onset IBD. While this study does not prove causation, it is another reason for good antibiotic stewardship.

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Pivotal Study: Guselkumab Efficacy in Ulcerative Colitis (QUASAR study)

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DT Rubin et al. Lancet 2024; 405: 33-49. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies

Background: “Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64.”

Methods:  “Two phase 3, randomised, double-blind, placebo-controlled studies (QUASAR phase 3 induction and maintenance) included randomised and treated adults with moderately to severely active ulcerative colitis (induction baseline modified Mayo score from 5 to 9) with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy.”

“The induction study primary population included 701 patients (guselkumab 200 mg given intravenously 60% [421 patients]; placebo 40% [280 patients]). The maintenance study primary population included 568 guselkumab induction responders randomly assigned to receive guselkumab 200 mg given subcutaneously every 4 weeks (190 [33%] patients) or 100 mg every 8 weeks (188 [33%] patients) or placebo (guselkumab withdrawal 190 [33%] patients).”

Key findings:

  • INDUCTION DATA AT 12 WEEKS:
At induction week 12
At induction week 12
Induction symptomatic endpoints -response noted in majority of guselkumab-treated patients by 4 weeks

MAINTENANCE DATA AT 44 WEEKS

Results and Discussion points:

  • “Symptomatic improvement was observed as early as induction week 1 (first assessed timepoint)”
  • “Greater reductions in C-reactive protein and faecal calprotectin concentrations with guselkumab induction compared with placebo were observed as early as induction week 4 (first assessed timepoint)”
  • “Guselkumab efficacy was shown in both biologic naive and JAK inhibitor-naive patients, and in patients with a history of inadequate response or intolerance to biologics or JAK inhibitors”
  • “Overall, 34% (129 of 378) of patients in the guselkumab groups achieved endoscopic
    remission     at maintenance week 44. Among the 180 patients in the guselkumab groups in clinical remission at maintenance week 44, 124 (69%) of 180 were in endoscopic remission”
  • “Symptomatic remission and deep symptomatic remission achieved with guselkumab induction was generally maintained to maintenance week 44 with guselkumab relative to placebo”
  • “The incidences of anti-guselkumab antibodies and NAbs were low in both the induction and maintenance studies…titres were low and did not affect serum concentration, efficacy, or safety”
  • “Head-to-head comparison data with other IL-23 antagonists are currently not available”
  • “Safety results were consistent with the known and favourable safety profile of guselkumab in its approved indications. Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation generally did not occur more frequently in patients treated with guselkumab versus placebo-treated patients”
  • Limitation: The primary analysis population for the maintenance study included only guselkumab induction responders following 12 weeks of intravenous treatment

My take: Overall, this is a pivotal study showing that guselkumab is an effective agent for moderately to severely active ulcerative colitis in those with and without prior treatments. More head-to-head studies are needed to determine the optimal positioning of therapies for UC. Currently, AGA guidelines (AGA Living Guideline for Moderate-to-Severe Ulcerative Colitis –The Good and The Bad) suggest that guselkumab should be considered in the top tier of medications used in patients naive to biologics/advanced therapies and in the second tier for those with prior biologic treatments.

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Efficacy of Anthocyanin-Rich Extract in Ulcerative Colitis

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L Beidermann et al. Nutrients. 2024;16(23):4197. Open Access! Efficacy and Safety of Anthocyanin-Rich Extract in Patients with Ulcerative Colitis: A Randomized Controlled Trial

First of all: Bilberries are similar to blueberries, but have red inner flesh rather than white flesh.

Background: The authors note that some small studies have shown that anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, has been effective for ulcerative colitis (UC)

“ACs have been associated with many protective biological effects, including anti-oxidative, anti-carcinogenic, antimicrobial, and anti-inflammatory properties [17,20,21]. Due to their phenolic structure, ACs exhibit an anti-oxidative capacity in vivo as they scavenge reactive oxygen species (ROS) [20,22], also a classical effect of 5-ASA [23]. After ingestion, ACs largely bypass absorption in the upper gastrointestinal tract, reaching the colon intact, where they are metabolized by microbiota through deglycosylation and further degraded into vanillic, protocatechuic, p-coumaric, gallic, and syringic acids (i.e., phenolic acids) [24]. ACs interrupt the pro-inflammatory signaling and are inhibitors of 5-lipoxygenase, a key enzyme implicated in the arachidonic acid pathway for the biosynthesis of active leukotrienes.”

Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Due to COVID-19’s effect on study enrollment, only 34 patients were randomized and only Eighteen ACRE and eight placebo patients could be analyzed (per protocol set)

Key finding:

  • Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo).
  • Fecal calprotectin (FC) dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035).

The authors state that the placebo group had an unusually high response and that improved FC with ACRE patients indicates efficacy in UC.

Figure 2
Figure 3

My take: This is a negative study (despite the secondary finding of improved FC at some timepoints). Importantly, the study did not demonstrate any harms in the ACRE group. It did help me understand more about bilberries!

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Efficacy of Mirikizumab in Ulcerative Colitis: LUCENT-3 Study Results

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BESands, et al.  Inflammatory Bowel Diseases, 2024. 30: 2024 2245–2258. Open Access! 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

In this LUCENT-3 study, the authors examined response at 2 years among patients who had response to treatment at 1 year; patients received 200 mg mirikizumab every 4 weeks. The authors stratified patients by induction response and by previous biologic exposure.

Key findings (from Figure 4):

HEMR= histologic-endoscopic mucosal remission
  • No new safety signals were identified, and the discontinuation rate due to adverse events was 2.8%

My take: It is good to see extended data for mirkizumab. Head-to-head trials, though, are needed to better determine which therapies are most effective.

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