EV Loftus et al. AP&T 2020; 52: 1343-1365. Full text: Long‐term safety of vedolizumab for inflammatory bowel disease
GEMINI long‐term safety (LTS) study results –initiated 2009:
- Enrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks. Total of 7999 patient years of vedolizumab exposure.
- Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients.
- There were no new trends for infections, malignancies, infusion‐related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy
- Conclusion from authors: “The safety profile of vedolizumab remains favourable with no unexpected or new safety concerns.”
Related blog posts:
AS Faye et al. Inflamm Bowel Dis 2020; 26: 1368-1376. Fertility Impact of Initial Operation Type for Female Ulcerative Colitis Patients (link includes video abstract)
Surgical options include Ileal pouch–anal anastomosis (IPAA), rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). Conclusions based on “a patient-level state transition microsimulation in TreeAge Pro:”… “Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20–30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar.” In older age group, RCEI’s increase rate of childbirth (28%), decrease time to childbirth (14 months) and 77% reduction in IVF are important factors.
Related blog posts:
R Tariq et al. Inflamm Bowel Dis 2020; 26: 1415-1422. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease
In this retrospective study with 145 patients, the overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. The authors concluded that “fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.”
Related blog posts:
Isle of Palms (July 2020)
D Piovani et al. Gastroenterol 2019; 157: 647-59. This study examined environmental risk factors for inflammatory bowel disease after extensive literature review and assessment of meta-analysis.
9 factors that were associated with increased risk of IBD:
- smoking (CD)
- urban living (CD & IBD)
- appendectomy (CD)
- tonsillectomy (CD)
- antibiotic exposure (IBD)
- oral contraceptive use (IBD)
- consumption of soft drinks (UC)
- vitamin D deficiency (IBD)
- Heliobacter species (non-Helicobacter pylori-like) (IBD)
7 factors that associated with reduced risk of IBD:
- physical activity (CD)
- breatfeeding (IBD)
- bed sharing (CD)
- tea consumption (UC)
- high folate levels (IBD)
- high vitamin D levels (CD)
- H pylori infection (CD, UC, and IBD)
EL Barnes et al. Inflamm Bowel Dis 2019; 1474-80. In this review which identified 12 studies and 4843 with an IPAA ( ileal pouch-anal anastomosis) for ulcerative colitis, 10.3% were ultimately diagnosed with Crohn’s disease. Link to full text and video explanation: The Incidence and Definition of Crohn’s Disease of the Pouch: A Systematic Review and Meta-analysis
EV Loftus et al. Inflamm Bowel Dis 2019; 1522-31. In this study with 2057 adalimumab-naive patients, “the proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates.” Full text: Adalimumab Effectiveness Up to Six Years in Adalimumab-naïve Patients with Crohn’s Disease: Results of the PYRAMID Registry
The following study was summarized in previous blog: Oral Antibiotics For Refractory Inflammatory Bowel Disease Full text link: Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease
Washington Park, Portland, OR
KP Quinn et la. Inflamm Bowel Dis 2019; 25: 460-71. This is a terrific review of evaluation and management of pouch disorders.
A Armuzzi et al. Inflamm Bowel Dis 2019; 25: 568-79. This prospective cohort study examined infliximab biosimilar in 810 patients (PROSIT cohort). This included 459 patients naive to anti-TNF therapy (group a) , 196 with previous exposure (group b), and 155 who were switched while on original infliximab (group c). At 12 months, patients without a loss of response were 71%, 64%, and 82% respectively in these three groups.
S Coward et al Gastroenterol 2019; 156: 1345-53. This study from Canada used population-based health administrative data from multiple provinces and then applied autoregressive integrated moving average regression to predict prevalence of IBD in 2030. Key point: “In 2018, 267,983 Canadians were estimated to be living with IBD, which was forecasted to increase to 402,853 by 2030.” This is approximately 1% of the population (981 per 100,000).
F Castiglione et al. Aliment Pharm Ther 2019; 49: 1026-39. This observational longitudinal study with 218 patients with Crohn’s disease who completed 2-years of anti-TNF treatment examined transmural healing via ultrasonography (≤3 mm bowel wall thickness). “Transmural healing was associated with a higher rate of steroid-free clinical remission (95.6%), lower rates of hospitalization (8.8%) and need for surgery 0%).” The authors conclude that transmural healing is associated with better long-term clinical outcomes than mucosal healing.
“Magic Fountain” Barcelona
B Kochar et al. Inflamm Bowel Dis 2018; 24: 1833-9. This study reviewed prospectively collected data from 2011-2015 involving 2390 Ileal Pouch Anal Anastomosis (IPAA) surgeries for ulcerative colitis in those ≥18 years of age. Two approaches were compared:
- ‘Traditional’ 2- stage IPAA where the pouch is created with the colectomy
- Or a 3-stage surgery where the pouch is created in a second surgery after the colectomy (delayed pouch creation)
- Delayed pouch creation were significantly less likely to have an unplanned reoperation (RR =0.42, CI 0.24-0.75) and less likely to have major adverse events (RR=0.72, CI 0.52-0.99)
- Those in the delayed pouch creation group were much less likely to be receiving chronic immunosuppression at the time of surgery –15% compared to 51% in 2-stage group
My take: Particularly for sicker patients, delayed pouch creation (3-stage procedure) is likely to be best approach.
Related blog posts:
A recent review (S Chang, B Shen, F Remzi. Gastroenterology & Hepatology 2017; 13: 466-75 Full text link: When Not to Pouch: Important Considerations for Patient Selection for Ileal Pouch-Anal Anastomosis) makes recommendations regarding Ileal pouch-anal anastomosis (IPAA) for Crohn’s disease and indeterminate colitis. Key points:
- In CD patients with isolated colitis and without perianal disease, “there were no differences in the rates of postoperative complications, pelvic sepsis, or pouch failure compared with UC patients” (GE Reese et al. Dis Colon Rectum 2007; 50: 239-50).
- Rates of pouch retention for CD (Table 2) ranged from 43% to 94% in 19 studies. Most of these studies had small numbers (less than 40 patients). In the two largest studies with 97 patients and 150 patients, both with ~10 year followup, pouch retention rates were 74% and 87% respectively.
- “Patients carrying the diagnosis of IC have pouch function on par with patients with UC, with no significant difference in the number of bowel movements…However, ..are more likely to develop CD of the pouch. Nevertheless, pouch failure rates among IC, IBD-unclassified, and UC are similar in multiple cohorts.”
- Rates of pouch retention for IC ranged from 73%-100% among the 13 cited studies, though only 2 studies reported rates less than ~90%. The two largest studies with ~340 patients had retention rates of ~95% and followup of 3.4 yrs and 10.2 years.
This review also discusses IPAA and other issues including obesity (which increases the likelihood of complications), sphincter dysfunction, elderly patients, and radiation therapy.
Of note, recent ESPGHAN IBD Porto Group guideline for surgical Crohn’s disease management in children (J Amil-Dias et al JPGN 2017; 64: 818-35) at first glance seems to be at odds with Chang et al recommendations:
- “Statement 8. Ileal pouch-anal anastomosis is not recommended when a patient has CD. (Agreement 100%)”
- The body of the report is more nuanced: “There is, however, recent growing evidence that supports highly selective use of restorative proctocolectomy with ileal pouch-anal anastomosis for CD. These patients have isolated colonic CD and no evidence of ileal or perianal involvement.”
To me, statement 8 should have been worded to include “except in limited circumstances.” As it stands now, it misleads those who do not carefully review the entire report.
My take: The report by Chang et al makes a strong case for its conclusion: “Although it is true that the diagnosis of CD is a potential contraindication to IPAA, patients with isolated Crohn’s colitis may thrive after pouch surgery. At this time, patients with isolated Crohn’s colitis (without perianal disease or small bowel involvement) have good pouch retention rates.” Their review prompted me to look more closely at the ESPGHAN IBD Porto Group guideline; their Statement 8 recommendation is, in fact, quite misleading.
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. 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.
Keyhole view , looking into the Rotunda UVa, of Thomas Jefferson (or TJ for those in the know)