Tag Archives: de-escalation

IBD Update -December 2020

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DHW Little et al. Am J Gastroenterol 2020;115:1768–1774. Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review (Thanks to Ben Gold for this reference)

In this systematic review, a total of 995 adult patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial.

Key findings:

  • Biologic dose de-escalation was associated with relapse rates as high as 50% at 1 year. Overall, clinical relapse occurred in 0%–54% of patients who dose de-escalated biologic therapy (17 studies).
  • Lower rates of relapse (10%–25%) were reported in studies involving patients with endoscopic and/or histologic remission
  • These results are in agreement with a previous meta-analysis, which found a 1-year risk of relapse after discontinuation of anti-TNF therapy of 36% in CD and 28% in UC ( Gisbert JP, et al.. Am J Gastroenterol 2016;111:632–47).

My take: This study shows that dose de-escalation of biologic therapy in IBD
seems to be associated with high rates of clinical relapse

C Chapuis-Biron et al. Am J Gastroenterol 2020;115:1812–1820. Ustekinumab for Perianal Crohn’s Disease: The BioLAP Multicenter Study From the GETAID (Thanks to Ben Gold for this reference too)

In this national multicenter retrospective cohort study in 207 adult patients with either active or inactive perianal Crohn’s disease (pCD) who received ustekinumab (2017-2018). The majority had received multiple biologics (~85% had at least 2 anti-TNF agents, 28% had received vedolizumab) and prior anal surgeries (mean 2.8).

Methods: Success of ustekinumab was defined by (i) clinical success at 6 months of treatment assessed by the physicians’ judgment, with (ii) no need for dedicated medical treatment for perianal lesions (antibiotics and/or topics) nor (iii) unscheduled surgical treatment. For perianal disease evaluation, clinical success was defined in the study protocol, by the absence of draining pus for fistulas, and no anal ulcers

Key findings:

  •  In patients with active pCD, success was reached in 57/148 (38.5%) patients.
  • Among patients with setons at initiation, 29/88 (33%) had a successful removal.
  • In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively.
  • The absence of ustekinumab optimization was associated with upper odds of success (OR 2.74). “We can suppose in our present study that optimization of treatment was needed in severe refractory patients with no or insufficient response to ustekinumab. Thus, in these nonresponders, success was not achieved despite optimization.”

My take (partly borrowed from authors): “This large multicenter dedicated study adds
substantial evidence to the growing literature on ustekinumab effectiveness in refractory CD.” For pCD, optimization of ustekinumab has a low likelihood of improving response.

Related blog posts -De-escalation:

Related blog posts -Ustekinumab/Crohn’s Disease:

Expert Guidance on Inflammatory Bowel Disease (Part 3)

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A recent issue of Clinical Gastroenterology and Hepatology focused solely on the clinical features and management of inflammatory bowel disease. Even for those with expertise in IBD, there is a lot of useful information and concise reviews of what is known.

Here are some of my notes from this issue (part 3):

RP Hirten et al. Clinical Gastroenterol Hepatol: 2020; 18: 1336-45. A User’s Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease

This article emphasizes the need for assessment of bowel disease activity before attempting de-escalation and provides a list of risk factors for flare-up off therapy.

Some of the Risk factors for Disease Flare with De-escalation:

  • Disease activity/abnormal biomarkers (CRP, WBC, Hemoglobin, Calprotectin)
  • Perianal disease
  • Penetrating disease
  • Extensive disease involvement
  • Abnormal bowel wall thickening on MRE
  • Young age at diagnosis
  • Short treatment duration
  • Prior surgeries

Key points:

  • In individuals on combination therapy, dropping immunomodulator therapy (but not biologic therapy) did NOT increase the short term risk of a flare up in a recent Cochrane review.  However, this did impact anti-TNF kinetics and lowers anti-TNF troughs.
  • With regard to stopping biologics, among patients in deep remission, the authors advise counseling patients (CD and UC) that stopping biologic agents results in a “40-50% relapse over the following 2 years that will further increase over time.”
  • Careful followup is recommended if a patient elects to stop biologic therapy. “CD and UC are progressive relapsing conditions…and approximately 80% of subjects” require re-initiation of biologic therapy with 7 years.”
  • “Repeat colonoscopy or imaging should be performed if a significant change in symptoms occurs or abnormal biomarkers are detected.”
  • In patients who resume infliximab, the authors advocate for an initial induction of 0, 4, and 8 weeks.  The presence of antidrug antibodies at week 2 “precludes drug administration and alternative agent should be started.”

Related blog posts:

M Kaur et al Clinical Gastroenterol Hepatol 2020; 18: 1346-55. Inpatient Management of Inflammatory Bowel Disease-Related Complications

This article reviews the approach to acute severe ulcerative colitis which has been discussed recently on this blog post and offers management recommendations for complications related to Crohn’s disease including abscesses, strictures/bowel obstruction.  With regard to abscess management, the authors note that medical therapy is more likely to be effective in those with a first-time abscess, spontaneous origin, right lower quadrant location, and smaller abscess size (<3 cm).  Stricture with upstream dilatation of bowel, multi-loculated abscesses and steroid use are features that make therapy less likely to be successful.

Related blog posts -ASUC:

Abscess-related blog posts:

EL Barnes et al Clinical Gastroenterol Hepatol 2020; 18: 1356-66. Perioperative and Postoperative Management of Patients With Crohn’s Disease and Ulcerative Colitis

This article reviews risk factors for disease recurrence after surgery, presurgical management (eg. minimize steroids, improve nutrition, do not delay surgery based on preoperative biologic exposure), postoperative strategies and management of pouchitis.

  • In those at high risk for postoperative disease recurrence, the authors advocate anti-TNF therapy plus an immunomodulator with colonoscopy at 6-12 months. In those at low risk, many are placed on no medications and have a colonoscopy at 6 months postoperatively.
  • The section on pouchitis lists alternatives to metronidazole and ciprofloxacin if these lose efficacy.  This includes amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, doxycycline and vancomycin.
  • Related blog post: What’s Going on With Pouchitis?

S Singh et al Clinical Gastroenterol Hepatol 2020; 18: 1367-80. Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric

A Levine et al Clinical Gastroenterol Hepatol 2020; 18: 1381-92. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases

  • The authors recommend more vegetables and fruits with CD (but low insoluble fiber if stricture present)
  • “Prudent to reduce intake of red and processed meat” with UC
  • “Prudent to increase dietary omega-3 fatty acids” from marine fish but not from dietary supplements with UC
  • ‘Prudent to use a low FODMAP diet for patients with persistent symptoms for CD and UC despite resolution of inflammation’

M Collins et al Clinical Gastroenterol Hepatol 2020; 18: 1393-1403.Management of Patients With Immune Checkpoint Inhibitor-Induced Enterocolitis: A Systematic Review

This study reviews colitis induced by immune checkpoint inhibitors which are similar to young patients with inherent CTLA4b deficiency.

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.

Reducing Inappropriate Proton Pump Inhibitor Usage & U.S. Children with COVID-19

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D Lin et atl. Clin Gastroenterol Hepatol 2020; 18: 763-6.  In a retrospective chart review, the authors examined pharmacy data from patients in the Harris Health System (Harris county -Houston, TX) which had more than 1.9 million outpatient clinic visits in 2017.

In January 2018, multiple efforts were made to try to reduce inappropriate proton pump inhibitor (PPI) usage.  This included grand rounds and system-wide emails to providers.  In addition, a suggested tapering algorithm (order in EPIC) was given to reduce the likelihood of rebound acid hypersecretion which could undermine the goal of stopping PPI.

Key points:

  • Taper: When ready to taper, start with “a PPI every other day for 2 weeks, followed by a PPI every 4 days for 2 additional weeks before discontinuation.”
  • De-escalation: Before educational intervention, in 2017, there were 66,261 unique PPI prescriptions. After educational intervention, in 2018, there were 55,322 unique PPI prescriptions (16.5% decrease). This equates to ~800,000 fewer capsules or pills dispensed in 1 calendar year
  • The most “important driver” for de-escalation was the initiation of the discussion by the ambulatory primary care provider
  • The authors recommend clinic followup within a month after starting de-escalation and gastroenterology evaluation for patients with severe symptoms or those refractory to PPI treatment

My take: This study indicates that 1 in 6 PPI users were able to de-escalate off treatment.  Physician initiative is crucial to improve appropriate medication use.

Related blog posts:

Recent study from JAMA Pediatrics (5/11/20) -Full text: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units

Of the 48 children with COVID-19 admitted to participating PICUs (14 hospitals)… Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation….At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively.

NY Times Summary of Study: Details of U.S. Children Severely Affected by Coronavirus

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