Highlights in IBD from Two 2019 Meetings: American College of Gastroenterology and United European Gastroenterology Week

Gastroenterology & Hepatology. December 2019 – Volume 15, Issue 12, Supplement 5

Excerpts from William Sandborn Commentary which are at the end of this supplement along with references:

Vedolizumab

In the VARSITY study (An Efficacy and Safety Study of Vedolizumab Intravenous [IV] Compared to Adalimumab Subcutaneous [SC] in Participants With Ulcerative Colitis), 769 patients with ulcerative colitis were randomized to a year of therapy with either adalimumab at the US Food and Drug Administration (FDA)-approved dose or vedolizumab at the FDA-approved dose…This shows that the idea that vedolizumab (and anti-integrin therapy) is slower-acting than anti-TNF therapy is not correct, and that both of these classes of drugs can work fairly quickly in a number of patients.

Dr Brian Bressler and colleagues looked at the effectiveness of anti-TNF therapy in the real world when used second line after failing first-line biologic therapy with vedolizumab…The study conducted by Dr Bressler and colleagues, which included both Crohn’s disease patients and ulcerative colitis patients, found that the results were fairly similar whether patients received first-line biologic therapy with an anti-TNF agent or whether patients received first-line therapy with vedolizumab… It is generally thought that vedolizumab is a safer therapy than anti-TNF therapy, so with the finding from this study, a reasonable treatment approach could be to start with vedolizumab and see if it works

Dr Christina Chambers and colleagues identified outcomes for pregnancy in 223 women, 53 of whom received vedolizumab. The researchers found that there were no major structural birth defects reported in the vedolizumab group, compared to 5.7% and 5.3% in the disease-matched group and healthy control group, respectively. Thus, there seemed to be no signal for an increased malformation risk in patients who were undergoing treatment with vedolizumab and became pregnant.

Adalimumab

The SERENE trials are a set of head-to-head trials, one for ulcerative colitis and one for Crohn’s disease, comparing standard-dose adalimumab to a more intensive induction regimen of adalimumab…

For both ulcerative colitis and Crohn’s disease, the SERENE trials showed that the current FDA-approved dosing regimen is effective and that more intensive induction therapy does not improve outcomes over time. Thus, there is no utility in giving high induction doses. 

Tofacitinib

Over 1000 patients who had been treated with tofacitinib were examined…during induction and maintenance of the placebo-controlled portion of the tofacitinib clinical trials, there were a total of 5 deep vein thrombosis and pulmonary emboli events. All 5 occurred in patients who were receiving placebo; none of these events occurred in patients who were receiving tofacitinib…[And] There was a total of 5 deep vein thrombosis and pulmonary emboli events during this long-term extension…Looking at the ulcerative colitis clinical trial data that I presented, it is somewhat reassuring that we did not see the same elevation in risk for deep vein thrombosis and pulmonary emboli that was seen in the high-risk rheumatoid arthritis patient population.

Mont Royal (Montreal)

IBD Updates November 2019

M Lowenberg et al. Gastroenterol 2019; 157: 997-1006. This LOVE-CD study, a prospective study with 110 patients with active Crohn’s disease, found that treatment with vedolizumab resulted in 29% and 31% corticosteroid-free clinical remission at weeks 26 and 52 respectively (CDAI <150).  Endoscopic remission, based on intent-to-treat analysis, was 33% and 36% at weeks 26 and 52.  Serum vedolizumab levels above 10 mg/L at week 22 were associated with endoscopic remission at week 26.

S Danese et al. Gastroenterol 2019; 157: 1007-18.  This VERSIFY trial, a phase 3b, open-label, single-group study of 101 patients with Crohn’s disease, found that treatment with vedolizumab resulted in 11.9% and 17.9%  endoscopic remission at week 26 and 52 respectively. Remission by MRE was 21.9% and 38.1% at those respective time points. No notable safety issues were reported.

N Khan et al. Clin Gastroenterol 2019; 17: 2262-8. Using a retrospective cohort of 54,919 patients with IBD followed by the VA System (2000-2018), the authors identified 467 patients with incident squamous cell cancer (SCC); median age ~70 years.  11 patients with SCC died from related-complications.  In this group, 8 had been exposed to thiopurines.   Thus, exposure to thiopurines increased mortality related to SCC compared to those exposed to mesalamine therapy, though the absolute risk among the entire cohort was less than 1 in 5000.  My take: Long-term use of thiopurines should be paired with dermatology evaluation and good skin care.

Pics from Mechandise Mart Light Show, Chicago

#NASPGHAN19 Selected Abstracts (Part 2)

Link to full NASPGHAN 2019 Abstracts.

Here are some more abstracts/notes that I found interesting at this year’s NASPGHAN meeting.

A study (poster below) from Cincinnati found that a vedolizumab level ≥34.8 mcg/mL at week 6 (prior to 3rd infusion) predicted clinical response at 6 months

Related blog posts:

The poster below reported a high frequency of eosinophilic disorders in children who have undergone intestinal transplantation. Related blog post: Eosinophilic disease in children with intestinal failure

This study from Boston indicates that acid suppression was not associated with improved outcomes in infants with laryngomalacia (eg. lower supraglottoplasy rates or lower aspiration rates.

Related blog posts:

The study below showed that “less than half of children who started the low FODMAP diet were able to complete the elimination phase.” This indicates the need for careful dietary counseling when attempting this therapy.

Related blog posts:

The abstract below showed that the dietary intake of children with inflammatory bowel disease, who were not receiving enteral nutrition therapy, was similar to healthy control children.

The next two studies provide some pediatric experience with tofacitinib in teenagers with inflammatory bowel disease (14-18 years of age).  The first poster had 12 children and reported a 67% clinical response rate (cohort with 5 with CD, 5 with UC, and 2 with IC).  The second poster had 4 of 6 with a clinical response and 3 in remission.

Related blog posts -Tofacitinib:

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.

#NASPGHAN19 Postgraduate Course (Part 5)

Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course.  There may be errors in omission or transcription on my part.

Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)

– Intestinal Inflammation Session

192 David T. Rubin, MD, University of Chicago Positioning the new IBD therapies: Merging experience with evidence

Some key points:

  • Ustekinumab escalation can increase response. Optimization in CD patients with loss of response led to recapture of response in 69% of patients
  • Tofacitinib –given black warning, will likely be used in more refractory patients
  • May be able retry a previous therapy (Chicago protocol in slide below)

As an aside, while Dr. Rubin is an excellent speaker, my view is that there are so many terrific pediatric IBD specialists, I would favor having a pediatric IBD specialist give this talk at our postgraduate course.  (Some might argue that adult IBD specialists would have more experience with emerging therapies.)

204 Anne Griffiths, MD, FRCPC, Hospital for Sick Children Immunosuppressive therapy in IBD: Can we de-escalate therapy?

  • High rate of relapse when biologic therapy is stopped.  Use of an immunomodulator may reduce the relapse rate when stopping an anti-TNF agent

215 Stacy Kahn, MD, Boston Children’s Hospital When it is not IBD … rare forms of intestinal inflammation

  • For patients with milder microscopic colitis, antidiarrheal agents can be given.  For more severe disease, budesonide is effective.

223 Edaire Cheng, MD, UT Southwestern Medical Center  Eosinophilic inflammation beyond the esophagus

 

Disclaimer: NASPGHAN/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. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society 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. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.

Vedolizumab versus Adalimumab for Ulcerative Colitis (part 2)

A previous blog post (Vedolizumab More Effective Than Adalimumb for Ulcerative Colitis) highlighted a preliminary report on the “VARSITY” study. The full report has now been published (BE Sands et al NEJM 2019; 381: 1215-26) and a little nuance is needed.

This double-blind, double-dummy randomized trial included 769 patients who underwent randomization to receive at least one dose of one of the study medications.

Key findings:

  • At week 52, clinical remission was higher in the vedolizumab group: 31.3% compared to 22.5% for adalimumab
  • Endoscopic improvement was better for vedolizumab: 39.7% compared to 27.7%
  • Corticosteroid-free remission was better for adalimumab: 21.8% compared to 12.6% for vedolizumab

Limitations:

  • dose escalation was not allowed during the study –this limitation likely favors vedolizumab compared to adalimumab
  • previous exposure to an anti-TNF agent was allowed in up to 25% of patients

My take:  In two of three key measures, vedolizumab outperformed adalimumab.  This study provides a rationale for vedolizumab to be considered a first-line agent.  That being said, in my clinical experience, infliximab is a much more frequently used anti-TNF agent in moderate-to-severe ulcerative colitis.  So a head-to-head study with infliximab would be of interest.

The image below shows histologic remission differences at week 52

 

Related posts:

IBD Articles -Briefly Noted

A Dige et al. Gastroenterol 2019; 156: 2208-16. This study evaluated the efficacy of freshly collected autologous adipose tissue injection for healing of perianal fistulas in Crohn’s disease.  The overall healing rate was 57% and the treatment had a good safety profile.

HK Somineni et al. Gastroenterol 2019; 156: 2254-65. The researchers found that DNA methylation patterns (from ~850,000 sites) in blood samples from pediatric patients with Crohn’s disease  (n=164) were associated with inflammation and resolved with treatment of inflammation; thus, the changes in DNA methylation are less likely to be a causative agent in disease development or progression and more likely a biomarker of inflammation.

OB Kelly et al. Inflamm Bowel Dis 2019; 25: 1066-71. Among 316 patients who underwent A/P CT scan for any reason, 49 (16%) had evidence of sacroilitis, indicating this is underdiagnosed in patients with IBD.

BG Feagan et al. Inflamm Bowel Dis 2019; 25: 1028-35. In a post hoc analysis of GEMINI 1 trial (n=769 patients: 149 placebo, 620 vedolizumab), a randomized placebo-controlled trial of vedolizumab for ulcerative coliis, compared to placebo ~40% more patients receiving a full induction of vedolizumab had a sustained clinical remission after 52 weeks of therapy.  Of patients in clinical remission at week 14, 66.5% achieved a sustained clinical remission at week 52 compared with 267% of placebo-treated patients based on partial Mayo score..  Sustained clinical remission was based on partial Mayo score and rectal bleeding subscore..