IBD Update Feb 2019

Briefly noted:

B Feagan et al. Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab. Alim Pharm Ther 2019 Jan;49(1):31-40. “While available data have not identified significant risks associated with a single switch between reference and biosimilar infliximab, the studies available currently report on only single switches and were mostly observational studies lacking control arms. Additional data are needed to explore potential switching risks in various populations and scenarios.”

MP Pauly et al. Incidence of Hepatitis B Virus Reactivation and Hepatotoxicity in Patients Receiving Long-term Treatment with Tumor Necrosis Factor Antagonists. Clin Gastroenterol Hepatol 2018; 16: 1964-73. Using data from 8887 adults, this retrospective review found  “HBV reactivation iin 39% of patients who were HBsAg+ before therapy, but not in any patients who were HBsAg-negative and anti-HBc+ before therapy.”

D Lauritzen et al. Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities? Inflamm Bowel Dis 2018; 24: 2599-2605. In a cross-sectional cohort of 56 children with IBD, the authors found 25% “had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease.” The authors note that plasma cystatin C is a useful biomarker for glomerular filtration as it less dependent on nutritional status; it is increased in the setteing of a decline in GFR.

L Pouillon et al. Mucosal Healing and Long-term Outcomes of Patients with Inflammatory Bowel Diseases Receiving Clinic-Based vs Trouhg Concentration-Based Dosing of Infliximab. Clin Gastroenterol Hepatol 2018; 16: 1276-83.  This retrospective study with patients who completed TAXIT maintenance phase found that patients who received trough-based infliximab dosing had a lower discontinuation rate of infliximab compared with clinic-based dosing (2 of 21 [10%]  vs. 10 of 27 [37%]).  However, both groups had >75% of patients able to continue infliximab for more than 3 years after the trial.

N Ouldali et al. Early Arthritis Is Associated With Failure of Immunosuppressive Drugs and Severe Pediatric Crohn’s Disease Evolution. Inflamm Bowel Dis 2018; 24: 2423-30. In this retrospective study with 272 patients with Crohn’s disease, 23.9% (n=65) developed arthritis and this was associated with failure of immunosuppressive drugs with OR of 6.9 after 2 years. In this study, immunosuppressive drugs refers to thiopurines and methotrexate.  By the completion of study, a much greater proportion of those with arthritis required biologic treatment (76% vs 32%, OR 4.3)

More advice on Proton Pump Inhibitors

L Laine, A Nagar. Am J Gastroenterol 2016; 111: 913-15.

This reference explains how these clinicians discuss the long-term use of proton-pump inhibitors with their adult patients.  Thanks to Ben Gold for this reference.  Here are a couple pointers:

  • “The recent studies about CKD (chronic kidney disease) and dementia, similar to many prior studies assessing PPI risk, are retrospective observational studies…This results in differences between PPI users and non-users in factors that may impact study outcomes and confound results.”
  • Gastroesophageal reflux disease: The authors suggest that PPIs for GERD can be stopped >2 weeks after symptoms resolve.  For infrequent symptoms, H2RAs, lifestyle modifications and intermittent PPIs often suffice.
  • Barrett’s esophagus: “observational sutdies suggest that PPIs may decrease progression to neoplastic Barrett’s esophagus”

WHAT WE TELL PATIENTS: “Because of inherent risk of bias and low effect sizes we cannot conclude that associations of PPIs and adverse outcomes such as dementia and CKD in recent observational studies are vailid…Nevertheless, we cannot conclude that risks do not exist…we need to ensure that benefits outweigh potential risk.  If PPIs are indicated, using the lowest effective dose and, if possible, intermittent rather than daily therapy..should decrease the risk of potential side effects.”

On the same topic, Paul Moayyedi (in Gastroenterology and Endoscopy News, August 2016): “Every study has shown that sicker patients tend to be prescribed PPIs…Sick patients tend to develop other illnesses so PPIs will be associated with about any disease you can imagine in a database.”  As such, he asserts that weak associations (OR <2) are usually due to cofounding factors.  “The only benefit [these studies]..have is that it is another opportunity to discuss with the patients about stopping their PPI therapy, as there are a significant proportion…on these drugs unnecessarily.”

purple flowers

The Liver –Front and Center

Before proceeding with today’s post, those who read yesterday’s post may be interested in Atul Gawande’s take on the NEJM checklist publication -here’s the link (from Atul Gawande’s twitter feed): bit.ly/1d6v31z

A recent review “Extrahepatic Complications of Nonalcoholic Fatty Liver Disease” (NAFLD)(Hepatology 2014; 59: 1174-97) seems to position the liver as the center of a multitude of problems rather than one of many associated problems.

It is known that NAFLD increases the risk of end-stage liver disease and hepatocellular carcinoma.  However, the majority of deaths among individuals with NAFLD are attributed to cardiovascular disease and malignancy.  This lengthy review describes in great detail the associations between NAFLD and the risk of developing cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and colorectal neoplasm.  The presence of NAFLD appears to convey an independent increase in risk for these conditions.

Key points:

  • “The aggregated evidence provides strong evidence that individuals with NAFLD are at increased “independent” risk of developing CVD.  The risk of CVD mortality may be greater in subgroups of subjects with NASH and advanced fibrosis, compared to those with simple steatosis.”
  • “USS-defined NAFLD is associated with a 2- to 5-fold risk of developing T2DM after adjustment of several lifestyle and metabolic confounders.”
  • “NAFLD (in particular, biopsy-proven NASH) is associated with a greater prevalence of CKD (20% to 50% of patients). USS-defined NAFLD carries a 1.5- to 2-fold adjusted risk of incident CKD.”
  • “A true causal relationship between and NASH and colorectal cancer cannot be confirmed.”
  • Other potential extrahepatic manifestations: hypothyroidism, polycystic ovarian syndrome, obstructive sleep apnea syndrome, and osteoporosis.

Take-Home Message: NAFLD has independent associations for greater risk of CVD, hyperglycemia, and malignancy.  Whether these associations are simply an epiphenomenon  of more aggressive metabolic syndrome or whether the liver injury primarily causes these additional risks remains unclear.

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