Vedolizumab and Extraintestinal Manifestations of Inflammatory Bowel Disease

A recent retrospective study( MC Dubinsky et al. Inflamm Bowel Dis 2018; 24: 1876-82) indicates that vedolizumab (VDZ) is likely to less effective than anti-TNF agents for extraintestinal manifestations of inflammatory bowel disease (IBD).

The authors used the MarketScan database (2102-2016).  For Crohn’s disease (CD) this included 756 treated with VDZ and 19584 treated with anti-TNF.  For ulcerative colitis (UC), this included 544 treated with VDZ and 8574 treated with anti-TNF.

Key findings:

  • Compared to patients receiving anti-TNF therapy, VDZ-treated CD patients were 28% more likely to develop “any EIMs” with an adjusted rate ratio of 1.49.  The adjusted rate ratio of developing specific EIMs: erythema nodosum  4.29, aphthous stomatitis 3.71, episcleritis/scleritis 2.51, arthropathy 1.45, primary sclerosing cholangitis (PSC) 7.79, and uveitis/iritis 2.89.
  • VDZ-treated UC patients did not have a statistically-significant increase in general for EIMs; though when looked at individually, there was increased incident rate ratios for some: apthous stomatitis 3.67, pyoderma gangrenosum 4.42, and PSC 3.44.

The authors findings are counter to their hypothesis that VDZ-treated patients would not have a significantly higher incidence of EIMs and that the EIMs would parallel course with IBD. To explain their findings, the authors note the following:

  • “EIMs may be more associated with systemic inflammation than previously thought.”
  • “Alternatively, the correlation between specific EIMs and underlying intestinal disease activity may be less tight than previously described.”
  • Anti-TNFs may control intestinal inflammation better than VDZ
  • VDZ-treated patients may have had more severe disease

While EIMs are more likely to develop on VDZ therapy, this study and prior RCTs do not show whether VDZ is effective in resolving EIMs.

My take: This retrospective study indicates that EIMs, including PSC, are more likely to occur in patients receiving vedolizumab. It is unclear whether this is related to the gut-specific control of inflammation with VDZ or whether there are patient characteristics responsible for this observation.

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Low Rate of Ocular Disease in Pediatric Crohn’s Disease

A recent study (S Naviglio et al. Inflamm Bowel Dis 2017; 23: 986-90) confirms that there is a low rate of ocular disease in pediatric inflammatory bowel disease (IBD); in this cohort, half had Crohn’s disease (CD) and half had ulcerative colitis.

In this single center study, 94 children with a median age of 13.4 yrs were offered ophthalmologic examination (2014-2016).  None of these patients reported ocular symptoms.  The authors assert that 70% had intestinal remission, though 64% had elevated fecal calprotectin levels (>100 mg/kg). Key finding: One patient (1.06%) had ocular finding of uveitis (previously diagnosed prior to study)

The authors indicate that hepatobiliary manifestations, present in 9, were the most common extraintestinal IBD manifestation (EIM). Arthropathy occurred in 8, cutaneous manifestations occurred in 6 and ‘metastatic’ CD occurred in 4.

My take:  Ocular disease is an infrequent EIM in pediatric patients with IBD.

Related articleK Hata et al. Inflamm Bowel Dis 2017; 23: 1019-24. This article found that patients with EIMs were more likely to have chronic pouchitis after colectomy for ulcerative colitis. Overall, chronic pouchitis developed in 3.3%, 7.6% and 16.6% at 2, 5, and 10 years respectively. Key finding: preoperative EIM yielded a HR of 4.52.

February Briefs

JM Powers et al. J Pediatr 2017; 180: 212-6. This retrospective study details a protocol for using intravenous ferric carboxymaltose (FCM) (Injectafer) in children.  This product has become available for adults in U.S. since June 2013; it had been available in Europe since 2009. In this retrospective study, 72 pediatric patients received FCM for iron deficiency anemia (off-label); there was a good safety profile and a good response with hemoglobin increasing from 9.1 to 12.3 (4-12 weeks post infusion).  FCM is a relatively costly IV iron formulation, but can be given over 15 minutes.

L Peyrin-Biroulet et al. Clin Gastroenterol Hepatol 2017; 15: 25-36.  This systemic review with more than 2800 patients showed that TNF antagonists were effective for extraintestinal manifestations of inflammatory bowel disease, including cutaneous disorders (eg.. pyoderma gangrenosum, erythema nodosum), hematologic problems (eg anemia), ocular disorders, and rheumatologic symptoms( eg. arthralgias/arthritis).

AE Mikolajczyk et alClin Gastroenterol Hepatol 2017; 15: 17-24. Useful review of the GI/Liver manifestations of autosomal-dominant polycystic kidney disease. “There is not a role for therapy [for the liver] in asymptomatic patients.” Other problems reviewed included pancreatic cysts, hernias, and diverticular disease. Related posts:

T Rajalahti et al. JPGN 2017; 64: e1-6.  Among 455 patients <18 with Celiac disease, anemia was noted in 18%. This resolved in 92% after one year of a gluten-free diet.  Anemia is associated with more severe histological and serological presentation. Related posts:

FL Cameron et al. JPGN 2017; 64: 47-55. This retrospective review of 93 children treated with infliximab and 28 children with adalimumab provides data on growth after anti-TNF therapy.  This study shows that anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty.

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Chattahoochee River

Chattahoochee River