22 // THE NEW GASTROENTEROLOGIST: INSIGHTS FOR FELLOWS & YOUNG GIS WINTER 2016
SPECIAL REPORT
like a smoking history. In the newly published clinical guidelines for
Barrett’s, ablative therapy or 1-year
surveillance have been suggested to
be equally acceptable options for patients with LGD.
8
Inflammatory bowel disease
Exciting new inflammatory bowel
disease (IBD) therapies came on the
horizon in 2015, with some that are
administered orally, which could
prove to be game changing (Table 1).
For existing therapies, focus remained
on employing drug-level monitoring
to prevent loss of response, which
occurs in half of patients started on
biologic agents. Post hoc analyses of
the SONIC and TAXIT trials show that
monotherapy with anti–tumor necro-
sis factor (TNF) drugs can be highly
successful if mucosal inflammation
can be neutralized quickly; as evi-
denced by adequate drug levels both
at the end of induction and during
the maintenance phase. Infliximab
target trough level of greater than 3.0
microg/mL at week 30 predicts both
long-term steroid-free remission and
mucosal healing (odds ratio, 3.34).
16
In the maintenance phase, levels between 3 and 7 microg/mL are considered optimal, with dose intensification
if levels are low.
17
Several studies highlighted known
malignancy concerns with thiopu-
rines (TPs) and reassuring data on
the safety of biologics. A large pop-
ulation-based study supported that
biologics alone do not increase over-
all risk of malignancy and that malig-
nancy risk for combination therapy
appears to be related to thiopurine
exposure.
18, 19 A meta-analysis of 18
studies reports that there is a sixfold
increased risk of lymphoma with
exposure to TPs especially in men
under 30 or patients more than or
equal to 50, with a number needed to
harm of 1/377.20 The good news is
that the risk is high only after more
than 1 year of exposure and goes
back to baseline if discontinued. So
how can we stop TPs for patients on
combination therapy? Safe de-escala-
tion was shown to be a possibility for
at least a subset of patients who ob-
jectively demonstrate well-controlled
disease and have adequate anti-TNF
trough levels, greater than 5 microg/
mL for infliximab.
21,22
In an effort to alter the natural history of IBD, treatment targets continued
to evolve in 2015, moving away from
symptom-based scores like Crohn’s
Disease Activity Index to more objective therapeutic targets of intestinal inflammation.
23, 24 Fecal calprotectin (FC),
a calcium-binding protein, may offer a
noninvasive and cost-effective target.
Two prospective studies of 135 and 86
postoperative Crohn’s disease patients
show that serial FC can indicate early
recurrence and hence, for low-risk patients, it is ideal for surveillance of recurrence.
25, 26 FC is also useful to make
management decisions in symptomatic
IBD patients (sensitivity, 0.88) if used
in the context of pretest probability
of endoscopic inflammation.
27 For instance, in a patient with high pretest
probability of endoscopic disease, an
elevated FC can give the gastroenterologist further confidence for escalating
therapy. Other clinical scenarios in
which FC could be employed include
predicting pouchitis for patients who
have undergone restorative procto-colectomy even before they become
symptomatic and differentiating IBD
from irritable bowel syndrome (IBS).
28
A meta-analysis of 12 studies showed
that an FC cutoff of 40 effectively rules
out IBD.
29
Male sex
More than 50 years of age
Life-long nonsmokers
Initial infectious prodrome
Antidepressant use
Four-hour gastric retention more than 20%
Obesity
Use of pain modulators
Abdominal pain (moderate to severe)
Severe GERD
Moderate to severe depression
Table
2
A large population-based study supported that biologics alone do not increase
overall risk of malignancy and that malignancy risk for combination therapy
appears to be related to thiopurine exposure.
