Tag Archives: acute severe ulcerative colitis

Treatments for “Bad” Inflammatory Bowel Disease (Part 3)

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D Tarabar et al. Inflamm Bowel Dis 2022; 28: 1549-1554. A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab

As noted previously, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Today’s post concludes several reviewed articles that focus on the problem of IBD that is not responding well to treatment.

Methods: Seventeen steroid-resistant adult UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Only 2 patients in this chort had failed infliximab therapy. The authors administered IV cyclosporine at a dose of “2 to 4 mg/kg/d IV for 7 days, titrated to a goal trough level of 300 to 400 ng/mL.” In those with a response, patients were started on oral therapy along with IV vedolizumab. During oral therapy (for 8 weeks), goal trough levels were 150 to 250 ng/mL (measured weekly).

Key findings:

  • Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab
  • At week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. 
  • At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission.
  • At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission.
  • Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively

My take: Cyclosporine is a fast-acting medication and thus appropriate as a salvage therapy in those with severe disease. Concerns for adverse effects have led most pediatric GIs to favor infliximab for refractory severe UC. However, in selected patients, it could be a useful “bridge” to slower-acting long-term treatments. It is possible (likely) that insurance issues would be less with cyclosporine than tofacitinib as a bridge therapy.

**An alternative agent to cyclosporine is tacrolimus. Hamel B, Wu M, Hamel EO, Bass DM, Park KT. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis. BMJ Open Gastroenterol. 2018;5(1):e000195 (“Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease” & 14% of U.S. Infected with COVID-19)

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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.

Island Ford National Recreational Area, Sandy Springs GA

Treatments for “Bad” Inflammatory Bowel Disease (Part 2) & Reassuring Data on Tofacitinib

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As noted yesterday, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Over the next few days, reviewed articles will focus on the problem of IBD that is not responding well to treatment. This article reports on the use of tofacitinib to avoid colectomy in children with severe ulcerative colitis.

BD Constant et al. JPGN 2022; 75: 724-730. Tofacitinib Salvage Therapy for Children Hospitalized for Corticosteroid- and Biologic-Refractory Ulcerative Colitis

This small (n=11) retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation.

Key findings:

  • Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib
  • The authors note that three patients started with TID dosing and eight received BID dosing (10 mg per dose). The higher dosing was influenced by a case control study by Bernstein et al which showed a 15% 90-day colectomy rate among adults with acute severe ulcerative colitis (ASUC), particularly those dosed at TID (Open Access: Clin Gastroenterol Hepatol 2021; 19: 2112-2120. Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study)
  • “Remission rates peaked at 12-16 weeks and decreased at 6 months…tofacitinib may …bridge to slower-acting and possibly safer long-term therapies such as ustekinumab or vedolizumab”
  • The median time to corticosteroid discontinuation was 89 days
  • No serious tofacitinib-related adverse events were observed

My take: Given the small numbers, this is clearly an area where cooperation (& ImproveCareNow) could be helpful in determining the safety and effectiveness of tofacitinib for pediatric ASUC. Also, if tofacitinib is used as a ‘bridge’ this is likely to present insurance coverage issues.

Related article:

Hoisnard L, Pina Vegas L, Dray-Spira R, et al. Annals of the Rheumatic Diseases Published Online First: 05 October 2022. doi: 10.1136/ard-2022-222824. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study Methods: This was a nationwide population-based cohort study (n=15,835) of the French national health data system, the exposed group initiating a JAKi and non-exposed group initiating adalimumab Key findings:  Risk of major adverse cardiovascular events (MACEs) for the exposed versus non-exposed group was not significant: HRw 1.0 (95% CI 0.7 to 1.5) (p=0.99), nor was risk of VTEs significant: HRw 1.1 (0.7 to 1.6) (p=0.63). This study provides reassuring data regarding the risks of MACEs and VTEs in patients initiating a JAKi versus adalimumab, including patients at high risk of cardiovascular diseases.

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From Crohn’s and Colitis Foundation, Georgia Chapter, December Newsletter: Donate to Cohen-Saripkin Fund

@MondayNightIBD and Acute Severe Ulcerative Colitis Algorithm

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A summary of the discussion and more detailed information on this topic from Gastroenterology and Endoscopy News (4/20/22): Open Access: ASUC: A Medical and Surgical Emergency Requiring Comprehensive, Timely Multidisciplinary Care

Lab workup per article:

For infliximab salvage therapy, the article recommends re-dosing at 3-5 days after initial dose.

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

“For Hospitalized Patients With ASUC, 5-ASA Adds No Value to Steroids”

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From Gastroenterology and Endoscopy News (4/25/22): Open Access: For Hospitalized Patients With ASUC, 5-ASA Adds No Value to Steroids

In the first prospective randomized study, presented at the 2022 Crohn’s & Colitis Congress and published in Inflammatory Bowel Dis (S Ben-Horin et al 2022;28 [suppl 1]:S14 CORTICOSTEROIDS AND 5ASA VERSUS CORTICOSTEROIDS ALONE FOR ACUTE SEVERE ULCERATIVE COLITIS: A RANDOMIZED CONTROLLED TRIAL), investigators at 10 centers in six countries randomly assigned 149 patients hospitalized for ASUC to receive daily doses of 300 mg of hydrocortisone (or equivalent methylprednisolone) alone or in combination with 4 g of mesalamine.

Key findings:

  • 72.6% of patients receiving combination corticosteroids with 5-ASA responded to treatment at one week compared with 76.3% of responders in the group receiving corticosteroids alone
  • “There were no differences in hospital length of stay between groups (median, 10 vs. nine days for the combination and monotherapy groups, respectively), the proportion of patients whose C-reactive protein level normalized (34.2% vs. 34.3%, respectively), or the proportion requiring colectomy within 90 days (4.9% vs. 4.5%, respectively).”
  • While 5-ASAs did not alter the trajectory of acute colitis, one other finding was a lower rate of biologic use (27% vs 47%, P=.07) at 90 days in those who continued to receive 5-ASA therapy at 90 days.

My take: 5-ASAs do not appear to be helpful during hospitalization for ASUC but may be beneficial as a maintenance therapy in some patients.

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

Early Assessment of Acute Ulcerative Colitis with ACE (Albumin, CRP, & Endoscopy)

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A recent study showed that admission albumin, CRP and early endoscopy were predictive of outcomes with ulcerative colitis patients admitted for a corticosteroids: RK Grant et al. Inflamm Bowel Dis 2021; 27: 451-457. Full text (free) The ACE (Albumin, CRP and Endoscopy) Index in Acute Colitis: A Simple Clinical Index on Admission that Predicts Outcome in Patients With Acute Ulcerative Colitis

This retrospective study had 235 patients (median age 38 years). 90% had endoscopy at a median of 2 days from admission. Key findings:

  • 155 of the 235 patients (66.0%) responded to steroids
  • 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician’s global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%).
  • Comparison with Truelove and Witts Score: 56 of 119 (47.1%) of those classed TWS severe did not respond to steroids. Previously TWS score of acute severe ulcerative colitis (ASUC), defined by at least 6 bloody stools per day plus at least 1 marker of systemic disturbance has been associated with a 19% risk of colectomy during admission.

My take: In patients with ulcerative colitis who present with low albumin and high CRP values, early escalation of medical therapy is highly likely; don’t forget to check a PPD or quantiferon Gold assay early on.

Related blog posts:

Azalea bush (March 2021)

A Definite Maybe: Antibiotics for Acute Severe Colitis

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D Turner et al. Inflamm Bowel Dis 2020; 26: 1733-1742. Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial

This randomized study with 28 children with acute severe ulcerative colitis (ASUC) (PUCAI > /= 65) tried to determine if antibiotics with IV corticosteroids resulted in improved outcomes compared to IV corticosteroids alone. Most in the antibiotic group received the following for 3 weeks:

  • Vancomycin 250 mg 4/day (if less than 8 years, then 125 mg 4/day)
  • Amoxicillin 50 mg/kg/day divided into 3/day dosing (max 500 mg/dose)
  • Metronidazole 5 mg/kg/dose 3/day (max 250 mg/dose)
  • Doxycycline 2 mg/kg/dose 2/day (children less than 7 years rec’d ciprofloxacin 10 mg/kg 2/day -max 250 mg/dose)

Key findings:

  • The mean day-5 PUCAI was 25 ± 16.7 in the abx/steroid combination group vs 40.4 ± 20.4 in the steroid monotherapy group (P = 0.037)
  • Median calprotectin values were lower in the abx combination group at day 5 (1202 vs. 2170, P=0.24) and at discharge (1210 vs 1840, P=0.695)
  • The need for 2nd line rescue therapy was low in both groups: 19% in abx group and 17% in the steroid group
  • Within 1 year, 3/16 (19%) in the abx combination group had had a colectomy compared with 2/12 (17%) in the steroid monotherapy.
  • The authors found no correlation between microbial features/microbiome at admissioin and clinical response 5 days later

In their discussion, the authors note that if antibiotics had a treatment benefit as high as 30% in avoiding second-line treatment (ie, 14% in intervention arm), “randomization of 1228 children would be required to show such a difference with a power of 80%.”

My take: I agree with the authors who state that “antibiotics cannot be routinely recommended until larger studies demonstrate a reduced need for second-line treatment or colectomy.”

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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

AGA Guidelines: Moderate to Severe Ulcerative Colitis

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Full Text: JD Feuerstein et al. Gastroenterol 2020; 158: 1450-61. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

Full Tex PDF: AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

 

Associated articles included the following:

  • Clinical decision support tool (1462-63)
  • PDF: Spotlight (summary -images above) (1464)
  • Technical Review (1465-96)

Key recommendations:

  • 2a. In adult outpatients with moderate to severe UC who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab rather than adalimumab, for induction of remission. Comment: Patients, particularly those with less severe disease, who place higher value on the convenience of self-administered subcutaneous injection, and a lower value on the relative efficacy of medications, may reasonably chose adalimumab as an alternative
  • 2c. In adult outpatients with moderate to severe UC who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib rather than vedolizumab or adalimumab for induction of remission.
  • 6. In adult outpatients with moderate to severe UC, the AGA suggests early use of biologic agents with or without immunomodulator therapy rather than gradual step up after failure of 5-ASA. Comment: Patients, particularly those with less severe disease, who place higher value on the safety of 5-ASA therapy and lower value on the efficacy of biologic agents or tofacitinib may reasonably chose gradual step therapy with 5-ASA therapy.
  • 10. In hospitalized adult patients with ASUC refractory to intravenous corticosteroids, the AGA suggests using infliximab or cyclosporine

Summary of recommendations:

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

A Little More Data on Antibiotic Cocktail for Pediatric Acute Severe Ulcerative Colitis

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A recent prospective study (D Turner et al. Inflammatory Bowel Diseases, izz298, https://doi.org/10.1093/ibd/izz298) with 28 children found improvement in 5-day PUCAI scores in patients who received quadruple antibiotics in combination with IV corticosteroids compared to those who received IV corticosteroids alone.

Link: Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial

Methods:

Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome.My t

Results

Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome

My take: Combination antibiotic therapy appears to improve disease activity in children with acute severe ulcerative colitis.  More and larger studies are needed to determine whether this is associated with improved long-term outcomes as well as which antimicrobials are optimal.

Related blog posts -ASUC:

Related blog posts -Calprotectin:

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

Year in Review: My Favorite 2019 Posts

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Yesterday, I listed the posts with the most views.  The posts below were the ones I like the most.

General/General Health:

Nutrition:

Liver:

Endoscopy:

Intestinal Disorders:

 

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.

 

Briefly noted: Mortality in Acute Severe Ulcerative Colitis

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C Dong et al. AP&T 2019 https://doi.org/10.1111/apt.15592

Link: Systematic review with meta‐analysis: mortality in acute severe ulcerative colitis

Key point:

  • “Six population‐based studies with 741,743 patients and 47 referral centre‐based studies with 2556 patients were included. The pooled 3‐month and 12‐month mortalities were respectively 0.84% and 1.01%”

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