S Jansson et al JPGN 2020; 71: 40-5. This retrospective study (1998-2008) showed that pediatric patients with extraintestinal manifestations (EIM) had more severe IBD course than patients with IBD without an EIM. EIM often had a temporal relationship with a relapse of IBD as well. Of 333 patients, 14 had an EIM at diagnosis and 47 had an EIM develop during followup.
PA Olivera, JS Lasa et al. Gastroenterol 2020; 158: 1554-73. This systematic review and meta-analysis ultimately included 82 studies with 66,159 patients (including those with IBD and other immune-mediated diseases) exposed to a JAK inhibitor; two-thirds of studies were randomized controlled trials. Key findings:
- Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81, 2.67, 0.89, and 0.48 per 100 person year respectively. After meta-analysis, the authors conclude that there is an increased risk of herpes zoster (RR 1.57), but all other adverse events were not increased among patients treated with JAK inhibitors
- Mortality was not increased in those receiving JAK inhibitors compared to placebo
Loebenstein, JD Schulberg. Gastroenterol 2020; 158: 2069-71. This case report describes a successful alternative anti-TNF rechallenge after infliximab induced Lupus in Crohn’s disease. The authors note that in a previous study, 14 of 20 IBD patents with drug-induced lupus secondary to an anti-TNF agent were rechallenged with an alternative anti-TNF agent and 13/14 tolerated rechallenge without recurrent lupus (Inflamm Bowel Dise 2013; 19: 2778-86).
These images show active disease prior to intervention. The article provides f/u images showing endoscopic remission after re-starting a different anti-TNF agent.
J Burisch et al. Clin Gastroenterol Hepatol 2019; 17: 2704-12. In this nationwide cohort from Denmark with 14,377 adult patients with IBD (median age 45.8 yrs) and 71,885 controls; immune-mediated diseases (IMID) were present in 22.5% of those with IBD.
Most common IMID:
- type 1 diabetes
- multiple sclerosis
- pyoderma gangrenosum
- rheumatoid arthritis
- ankylosing spondylitis,
- primary scelorsing cholangitis,
- primary biliary cholangitis
- Graves’ disease
- Patients receiving infliximab were at a reduced risk of developing an IMID with aOR of 0.52 for Crohn’s disease (CD) and 0.47 for Ulcerative Colitis. (UC)
- 80.3% of IMID were noted prior to onset of IBD
- The presence of IMID was associated with an increased risk of surgery in patients with CD with aOR of 2.30 but not in patients with UC
My take: About 1 in 4 patients with IBD have at least 1 other immune-mediated disease. The presence of an immune-mediated disease is associated with a higher likelihood of needing a biologic therapy and with surgery in patients with Crohn’s disease. In patients with numerous immune-mediated diseases, one needs to consider the possibility of other etiologies (eg. CTLA4 defiency)
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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.
- 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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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 article: K 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.
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 al. Clin 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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