Category Archives: Gastroenterology

IBD Shorts: Pediatric Cost Savings with Biosimilars and Multiple Biosimilar Switch Data

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GA Morris et al. Inflamm Bowel Dis 2022; 28: 531-538. Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money

Key findings:

  • Biosimilar utilization initiation increased from a baseline of 1% in June 2019 to 96% by February 2021 among eligible patients; 20% of all patients (n-98) had insurance which preferred originator product
  • Estimated cost savings over the project duration were nearly $381,000 (average sales price) over the 20 month study

My take: The introduction of biosimilars have resulted in huge cost savings. In addition, for infliximab, the originator product price has also dropped substantially (more than 60% in some locations)

J Hanzel et al. Inflamm Bowel Dis 2022; 28: 495-501. Open Access: Multiple Switches From the Originator Infliximab to Biosimilars Is Effective and Safe in Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study 

Methods: This was a prospective multicenter cohort study of adult IBD patients (n=176) who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3).

Key findings:

  • At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively.
  • There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups.

My take: This study did not identify detrimental effects from multiple successive switching and switching between biosimilars of IFX. Longer followup and more clinical experience will be needed to confirm these findings.

Guselkumab: Expanding the GALAXI of Treatments for Crohn’s Disease

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WJ Sandborn et al. Gastroenterol 2022; 162: 1650-1664. Open Access: Guselkumab for the Treatment of Crohn’s Disease: Induction Results From the Phase 2 GALAXI-1 Study

Background: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis.

Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients with moderate to severe Crohn’s disease 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. n=309 with ~50% having disease refractory to prior biologics

Key findings:

  • At week 12, significantly greater reductions in Crohn’s Disease Activity Index from baseline (least squares means: 200 mg: –160.4, 600 mg: –138.9, and 1200 mg: –144.9 vs placebo: –36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo
  • Improvement compared to placebo was evident as early as week 4
  • Safety event rates were generally similar across treatment groups

My take: This is an exciting time for practitioners taking care of patients as there are an increasing number of pharmacologic and dietary treatments for inflammatory bowel disease. With guselkumab, there may be an overlapping mechanism with ustekinumab which targets IL-12/23.

Related blog post: Emerging Data on Risankizumab for Crohn’s Disease

ENTERPRISE Study: Vedolizumab for Perianal Fistulizing Crohn’s Disease

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DA Schwartz et al. Clin Gastroenterol Hepatol 2022; 20: 1059-1067. Open Access: Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease: ENTERPRISE Study

Methods: “Patients with moderately to severely active CD and 1–3 active perianal fistulae (identified on magnetic resonance imaging [MRI]) received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ + wk10)… Enrollment was stopped prematurely because of recruitment challenges”

Key findings:

  • “Rapid and sustained fistula closure was observed; 53.6% (VDZ, 64.3%; VDZ + wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ + wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30”
  • “MRI healing, defined as the disappearance of T2 hyperintensity signal and absence of gadolinium contrast enhancement,3 was not reached in this study…gadolinium contrast enhancement showed improvement at week 30…MRI studies have shown that internal fistulae healing lags behind clinical remission by a median of 12 months”
Figure 1
Figure 2 B

The study findings are limited by relatively small size and lack of control group (eg. placebo or seton/antibiotic group). However, the rate of response in this study is significantly higher than placebo studies which have shown “~1 in 6” who experienced fistula closure.

My take: Vedolizumab is another option for treating Crohn’s disease with perianal fistula. Both regimens in this study were associated with response, though the additional 10-week dose (in one group) did not improve outcomes.

Related blog posts:

Tweetorial: Refractory Gastroparesis

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Tweetorial from “The Emoroid Digest”(posted 5/2/22):

Related blog posts:

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.

How To Achieve Helicobacter Pylori Cure Rates of >95%

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Related to yesterday’s blog, here is an SNL commercial for the “Koohl” toilet (also with Benedict Cumberbatch) in 2016: SNL Koohl Toilet

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DY Graham, SF Moss. Am J Gastroenterol 2022. 117: 524-528. Antimicrobial Susceptibility Testing for Helicobacter pylori Is Now Widely Available: When, How, Why

Key points:

  • Susceptibility testing for H pylori is widely available in the U.S. and should help optimize treatments to get success rates >95%. Testing is now available for the most common treatment antibiotics: amoxicillin, metronidazole, tetracycline, levofloxacin, clarithromycin, and rifabutin.
  • Handling/shipping specimens properly is important with susceptibility testing
  • The authors recommend a PPI which is minimally-affected by CYP2C19 metabolism, namely rabeprazole or esomeprazole.
  • Provide careful instructions to patient/family regarding treatment

Susceptibility Testing Labs (see Table 1):

  • Quest: Our Quest representative indicated code: 36994 (H. pylori culture with reflex to susceptibility). Preferred Specimen: 3 mm Gastric/Antral or Duodenal biopsy collected in Brucella broth or Trypticase Soy Broth (TSB) with 10-20% glycerol
  • LabCorp: Helicobacter pylori Culture Test Code Test Code 180885
  • ARUP: Helicobacter pylori Culture Test Code 2006686
  • Culture (Catalog HELIS) or Stool PCR testing (Catalog HPFRP) can be done by Mayo Clinic
  • Reflex stool testing as well as PCR gastric testing from formalin is available through by American Molecular laboratories

A treatment algorithm is listed:

  • In the absence of highly effective empiric treatment or after treatment failure, the authors recommend susceptibility testing.
  • If clarithromycin susceptible, then a 14-day clarithromycin triple therapy course is recommended
  • If clarithromycin resistant but metronidazole susceptible, then 14-day metronidazole triple therapy
  • If resistant to both clarithromycin and metronidazole, then either a 14-day bismuth quadruple therapy, or a rifabutin triple therapy are preferred. However, if H pylori organisms are levofloxacin susceptible, then 14-day levofloxacin triple therapy may be a good option.
  • The authors recommend quinolone therapy only in the setting of susceptibility testing due to the FDA warnings about long-term adverse effects.

My take: Perhaps H pylori susceptibility testing availability needs to be a quality metric for hospitals and endoscopy centers.


Related blog posts:

SERENE Study: Does a Higher Induction Dose of Adalimumab Help for Crohn’s Disease?

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GR D’Haens et al. Gastroenterol 2022; DOI:https://doi.org/10.1053/j.gastro.2022.01.044. Open Access: Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results

Methods: In this phase 3, randomized, double-blind, multicenter trial, eligible adults were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Endoscopic results were interpreted by a central reviewer.

Key Findings:

  • Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462).
  • There was a high proportion of patients (>70%) who achieved corticosteroid-free clinical remission after an early corticosteroid taper beginning at week 4
  • Week 56 efficacy was similar between clinically-adjusted (CA) and therapeutic drug monitoring (TDM).  28% of patients in the CA group and 39% of TDM had their dose escalated.
  • Safety profiles were comparable between dosing regimens.

In the discussion, the authors wade into the topic of TDM for adalimumab:

“Results from the exploratory SERENE CD study suggesting there is no clinical benefit of a proactive TDM strategy over a CA strategy for optimizing adalimumab maintenance dosing align with the results from previous studies evaluating TDM of anti–tumor necrosis factor therapies in adult patients with inflammatory bowel disease. In the TAXIT study, proactive TDM was not superior to CA dose optimization for achieving remission at 1 year in patients with CD or ulcerative colitis.24 Similarly, in the TAILORIX study of patients with CD, proactive TDM failed to improve clinical and endoscopic remission rates over a CA approach.25 In contrast, proactive TDM led to a higher clinical remission rate than did reactive TDM among pediatric patients with CD in the PAILOT trial, but this trial was nonblinded and lacked endoscopic assessments.26“

My take: This study shows that standard induction performed as well as higher dose induction in adults with Crohn’s disease. Also, this study found that TDM did not improve response at 56 weeks in adults. Due to differences in body size and metabolism, the exact role for TDM in pediatric patients needs further study.

Related blog posts:

HIR =high dose induction regimen, SIR =standard induction regimen

Upadacitinib Receives FDA Approval to Treat Adults with Ulcerative Colitis

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Pharmaceutical Technology (3/17/22): FDA grants approval to AbbVie’s Rinvoq for ulcerative colitis treatment

An excerpt:

The US Food and Drug Administration (FDA) has granted approval to AbbVie’s Rinvoq (upadacitinib) to treat adult patients with moderate-to-severe active ulcerative colitis (UC).

A selective inhibitor of Janus kinase (JAK), Rinvoq is indicated to treat UC patients who had reduced response or are not tolerant to one or more tumour necrosis factor (TNF) blockers.

Per David Rubin: This treatment is a once a day oral pill. In adults, induction consists of 45 mg daily for 8 weeks, then 15 mg or 30 mg for maintenance treatment.

Related blog post: Emerging IBD Treatment: Selective Jak Inhibitor, Upadacitinib 

Shem Creek, SC at dusk

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.

Two Studies for Eosinophiles

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ES Dellon et al. Clin Gastroenterol Hepatol 2022; 20: 535-545. Open Access: Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab

Key findings:

  • GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis—an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD.
  • Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases.

The 2nd article’s abstract was posted on this blog in July 2020 (Phase 3 Trial of Budesonide for Eosinophilic Esophagitis). Here is the published citation and graphical abstract:

I Hirano et al. Clin Gastroenterol Hepatol 2022; 20: 525-534. Open Access: Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial

Internet Survey: Lots of People Have Rumination

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A Josefsson et al. Gastroenterol 2022; 162: 731-742. Open Access: Global Prevalence and Impact of Rumination Syndrome

Key findings:

  • Using internet surveys from 26 countries (54,127 subjects), the authors identified an overall prevalence of rumination syndrome of 3.1% (Rome IV criteria)
  • Factors independently associated with rumination syndrome were depression (odds ratio [OR], 1.46), anxiety (OR, 1.8), body mass index (OR, 1.04), and female sex (OR, 1.19)
  • Limitations: this was “an Internet survey with self-reported symptoms. In clinical practice, investigations, including endoscopy and esophageal manometry, are often carried out, so we cannot completely exclude that some subjects had other conditions, misclassified as rumination syndrome” (especially reflux)
  • As noted in the commentary (pgs 696-697), the prevalance drops to 0.122% in those with daily symptoms, which is common in tertiary referral centers, the prevalence drops to 0.122%

My take: Rumination syndrome is common and likely underdiagnosed.

Related blog posts:

New Therapy for Crohn’s Disease: Mirikizumab

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Because our office is one of the centers participating in a mirikizumab study for adolescents, I was particularly interested in seeing the published results of a phase 2 study in 191 adults.

BE Sands et al. Gastroenterol 2022; 162: 495-508. Open Access: Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn’s Disease

Summary Video Link (worth a watch!): Summary of Mirikizumab Study (4:25 minutes)

Background: “Mirikizumab (LY3074828) is a humanized immunoglobulin G4 (IgG4)–variant monoclonal antibody that binds specifically to the p19 subunit of IL23 and has demonstrated efficacy in psoriasis and ulcerative colitis, and is currently in phase 3 testing for psoriasis, ulcerative colitis, and CD. We evaluated the efficacy and safety of mirikizumab for the treatment of patients with moderately-to-severely active CD”

Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12.

**approximately two thirds of participants had received biologic therapy and approximately half of all patients in this trial having experienced at least 1 biologic failure

Key findings:

  • At Week 12, endoscopic response was significantly higher for all mirikizumab groups compared with placebo (PBO) (200 mg: 25.8%, P = .079; 600 mg: 37.5%, P = .003; 1000 mg: 43.8%, P < .001; PBO: 10.9 %). 
  • Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C (combined IV groups) and SC (subcutaneous) groups , respectively. See 4th and 6th slides below which show that those with response at 12 weeks continued with response at 52 weeks.
In the Non-Randomized group which included non-improvers and placebo, they received
the highest dose, 1000 mg. A significant number of non-improvers responded at week 52.

My take: In this study of adults, with moderate to severe Crohn’s disease, Mirikizumab showed good efficacy and safety at both 12 weeks and 52 weeks. Because about half of the participants were biologic failures, this indicates that this agent shows promise in those with refractory disease.