that are known to modulate cardiovascular risk, like obesity. Given these
methodological weaknesses, PPIs
should not be discontinued for fear of
cardiovascular complications in patients with a legitimate indication for
acid suppression. However, infection
risk from PPI use remains a valid risk.
In a study of 188 cirrhotic patients
hospitalized for an index infection,
it was reported that PPI use was an
independent predictor (odds ratio,
2.94) of development of a different infection within 6 months of follow-up.
A small recent trial (n = 6) may pro-
vide biological plausibility of infection
risk with PPI therapy by showing that
– even in healthy subjects – PPI use
increases Enterococcaceae and Strep-
tococcaceae taxa that are associated
5 In summary, these
studies show that we should critically
evaluate use of PPIs and discontinue
them if there is no indication for their
In 2015, we also arrived at a better
understanding of the behavior of
dysplasia in patients with Barrett’s
esophagus. A large study of more
than 4,900 patients showed that increasing Barrett’s length and a higher baseline pathologic grade were
associated with an increased risk of
esophageal adenocarcinoma (EAC).
In another study of 125 patients with
low-grade dysplasia (LGD), radiofrequency ablation (RFA) reduced
progression to high-grade dysplasia
(HGD)/EAC from 26% to 1.5%, with
a NNT = 4.
7 Multivariate analysis
from this elegant study showed that
progression of LGD was linked to
nodularity and multifocality – providing insight as to which LGD cases
should be targeted for RFA. In our
practice, we are performing RFA on
all patients with HGD and patients
with LGD (after confirmation by two
GI pathologists) that is persistent
on endoscopic follow-up, especially
when there are additional risk factors
Vermeire et al.,
moderate to severe
ulcerative colitis (UC)
Humanized monoclonal B7 integrin antibody antagonizing egress of
lymphocytes from mucosal vasculature. Double-blinded placebo
controlled phase II RCT, n = 124.
Clinical remission in 21% (8/39) at week 10
(P < .05) for 100 mg. More effective in anti-TNF-naive subjects, so further trials may
enhance remission rates.
Lang et al.,
Add-on curcumin for
Inhibits TNF and nuclear factor-kappaB secretion, activates STAT- 3
and p38 mitogen-activated protein kinase and TH1 cytokines. Double-
blinded placebo controlled phase I trial, n = 50.
53.8% achieved clinical remission at week
4 (P = .01). Clinical response 65.3% vs.
12.5% and endoscopic remission 38% vs. 0%
receiving placebo (P = .04).
Sandborn et al.,
foam enema for
ulcerative proctitis or
Anti-inflammatory effect from high potency second generation
corticosteroids. Two randomized double-blinded placebo controlled
phase III studies, n = 546.
Remission (endoscopic or clinical) achieved
at week 6 in 38.3% vs. 25.8% in proctitis and
44% vs. 22.4% in proctosigmoiditis.
moderate to severe
Oral oligonucleotide that hybridizes to human SMAD 7 messenger
RNA to increase immunosuppressive TGFB1.
Multicenter randomized double-blinded placebo controlled phase II
study, n = 166.
Clinical remission (CDAI score) at day 28
was 65% in the 160-mg group vs. 12% in the
10-mg group (P < .001).
Molendijk et al.,
cells for perianal
Local administration of multipotent cells able to down-regulate mature
dendritic cells and promote tissue healing. Randomized double-
blinded phase II placebo controlled dose escalating clinical trial,
n = 21.
Healing observed in (66.7%; 85.7%; and
28.6% in groups 1; 2; and 3 vs. 33.3% in
placebo P = .06).
Fedorak et al.,
VSL#3 for preventing
recurrence of post-
High number of viable bacteria (900 billion/sachet) and a mixture of 8
different bacteria generating a probiotic effect. Randomized placebo-
controlled double-blinded multicenter study, n = 120.
Reduced inflammatory cytokine levels at
day 90 (P < .05). Endoscopic recurrence was
not different than placebo group. Trend for
protective effect if used in early post-op
toward endoscopic recurrence (P = .09).
Yoshimura et al.,
AJM300 for induction
therapy for moderately
Oral alpha4 integrin antagonist in patients with IBD. Double-blind
placebo-controlled phase 11a study, n = 102.
Clinical response rates were 62.7% at week
8 in the AJM300 group as compared to 25%
with placebo (OR = 5.35; P = .0002).