News
Digestive Disease Week 2018
Subcutaneous biosimilars
A novel subcutaneous formulation
of the infliximab biosimilar CT-P13
might be a more convenient option
for patients with Crohn’s disease, if
results presented by Stefan Schreiber
(Kiel, Germany) and colleagues are
confirmed in an ongoing formal
efficacy trial. 44 patients with active
Crohn’s disease were treated with
intravenous CT-P13 at weeks 0 and 2,
and at week 6 were randomly assigned
to one of four cohorts—one with
continued dosing of intravenous
CT-P13, or one of three different doses
of subcutaneous CT-P13. All patients
received treatment for 30 weeks.
Efficacy measures—including change
from baseline in the Crohn’s disease
activity index and clinical remission—
were similar in those receiving
subcutaneous CT-P13 compared
to those with intravenous CT-P13,
as were safety profiles. A lower
proportion of patients were positive
for anti-drug antibodies following
treatment with subcutaneous CT-P13
than with the intravenous form­
ulation. Pharmacokinetic and pharma­
codynamic modelling suggested
that subcutaneous and intravenous
formulations were similar in patients
with active Crohn’s disease.
PPI-refractory heartburn
Up to 40% of patients with gastro-
oesophageal reflux disease treated
with proton pump inhibitors
(PPIs) continue to have symptoms.
Stuart Spechler (Dallas, TX, USA)
and colleagues presented the results
of a randomised trial comparing
medical and surgical treatments for
patients with gastro-oesophageal
reflux disease refractory to PPIs.
Patients (n=78) were randomly
assigned to receive surgical treatment
(laparoscopic Nissen fundoplication;
n=27), active medical treatment
(omeprazole 20 mg twice daily plus
baclofen titrated up to 20 mg three
times daily, followed by desipramine
www.thelancet.com/gastrohep Vol 3 August 2018 531
titrated up to 100 mg at bedtime
for baclofen failures; n=25), or
placebo medical treatment (active
omeprazole 20 mg twice daily with
placebo baclofen and desipramine;
n=26). The primary outcome—
success rate at 12 months, defined as
50% or greater improvement in the
GERD-heath-related quality of life
score—was achieved by 18 (67%) in
the surgical group, seven (28%) in the
active medical group, and three (12%)
in the placebo group (p=0·007 for
surgery vs medical treatment and
p<0·0001 for surgery vs placebo).
Serious adverse events occurred in
four patients in the surgical group,
four in the active medical treatment
group, and three in the placebo group.
AMG 714 for coeliac disease
Markku Maki (Tampere, Finland) and
colleagues presented the results of a
phase 2A, double-blind, randomised
controlled trial of AMG 714, an anti-
interleukin-15 monoclonal antibody,
for amelioration of the effects of
gluten consumption in patients
with coeliac disease. Patients were
randomly assigned (1:1:1) to receive
150 mg AMG 714, 300 mg AMG 714,
or placebo in six subcutaneous doses
over 10 weeks. Between weeks 2 and
12, patients received a high-dose
gluten challenge of around 2·5 g per
day (n=49), except for those who had
mucosal atrophy at baseline (n=11).
The primary outcome—change in
villous height to crypt depth ratio—
among those who underwent gluten
challenge was –61% in the placebo
group, –62% in the 150 mg AMG 714
group, and –55% in the 300 mg group
(–16%, –6% and –3%, respectively, for
those who did not undergo gluten
challenge); there was no significant
difference between groups. The
300 mg group reported significant
improvement in the Celiac Disease
Patient-Reported Outcome score
(p=0·02), and the Physician Global
Assessment score (p=0·01). There were
no serious adverse events or safety
signals in the study.
Christophe Cellier (Paris, France)
and colleagues also presented results
from a phase 2A, double-blind,
placebo-controlled trial of AMG 714 in
patients with refractory coeliac disease
type II (also known as pre-enteropathy-
associated T-cell lymphoma), a
rare small bowel lymphoma that
primarily arises as a complication of
coeliac disease. Patients (n=28) were
randomly assigned (2:1) to receive Published Online
8 mg/kg of AMG 714 or matching June 13, 2018
http://dx.doi.org/10.1016/
placebo (seven intravenous doses S2468-1253(18)30202-4
over 10 weeks). The primary endpoint Digestive Disease Week 2018
of reduction in intestinal aberrant took place in Washington, DC,
intra-epithelial lymphocytes did not USA, on June 2–5, 2018
differ significantly between groups,
but AMG 714 was associated with
interruption in disease progression and
improvement in symptoms. Six serious
adverse events were reported (five in
the AMG 714 group and one in the
placebo group); mild nasopharyngitis
was the most common adverse
reaction in the AMG 714 group.
Mirikizumab for ulcerative
colitis
The pro-inflammatory cytokine
interleukin 23 is involved in inflam­­
matory bowel disease patho­
genesis, and blockade of the
interleukin-23 pathway has been
shown to have efficacy in Crohn’s
disease. In a multicentre, phase 2,
double-blind, placebo-controlled
trial, William Sandborn (San Diego,
CA, USA) and colleagues assessed the
safety and efficacy of mirikizumab,
an anti-interleukin-23 antibody, for
treatment of moderate-to-severe
ulcerative colitis. Patients were
randomly assigned (1:1:1:1) to receive
placebo (n=63), 50 mg (n=63) or
200 mg (n=62) mirikizumab with a
possibility of exposure-based increases,
or fixed-dose 600 mg mirikizumab
(n=61) intravenously at weeks 0, 4, and
8. At week 12, the clinical remission
rate (the primary outcome) was
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significantly greater in the mirikizumab
200 mg group (23%; p<0·01), but not
in the 50 mg (16%) or 600 mg groups
(12%), than in the placebo group (5%).
Rates of serious adverse events and
treatment-emergent adverse events
were similar across treatment groups.
Low-volume bowel preparation
A ready-to-drink, low-volume bowel
preparation of a split-dose oral sodium
picosulfate, magnesium oxide, and
citric acid solution was non-inferior
to a split-dose powder solution,
according to a phase 3 trial presented
by Lawrence Hookey (Kingston,
ON, Canada) and colleagues.
901 participants were randomly
assigned to receive either the oral
solution (n=448) or the powder
(n=453). The primary endpoint—
the proportion of participants with
excellent or good ratings for bowel
cleansing on the Aronchick scale—was
noted in 87·7% (95% CI 84·3–90·6)
participants in the oral solution
group and 81·5% (77·6–84·9) in
the powder group (difference 6·3%,
95% CI 1·8–10·9; p=0·0067). No
serious treatment-emergent adverse
events related to the study treatments
were reported, and any adverse
events possibly related to the study
intervention were reported by 13·2%
participants in the oral solution group
and 16·8% of those in powder group.
FMT for IBS
Tom Holvoet (Ghent, Belgium) and
colleagues reported the results of a
double-blind, placebo-controlled trial of
faecal microbiota transplantation (FMT)
for irritable bowel syndrome (IBS) with
predominant abdominal bloating.
Patients were randomly assigned (2:1)
to transplantation with fresh donor
stool (n=42) or with placebo (patient’s
own frozen stool; n=22). Donors (n=2)
were selected based on having a high
microbial richness and yielding good
clinical results in a preliminary pilot
trial, and were regularly screened
for infectious diseases. The primary
outcome—self-reported improvement
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of overall IBS symptoms (and
abdominal bloating in particular)
12 weeks after transplantation—was
achieved in 49% in the FMT group
versus 29% in the placebo group
(p=0·004). There were no significant
differences in efficacy between donors.
Screening for serrated polyps
Serrated lesions are often precursors to
post-colonoscopy interval colorectal
cancers, and are considered difficult to
detect. Sunil Dolwani (Cardiff, UK) and
colleagues presented findings from
the Bowel Screening Wales colorectal
cancer screening programme,
designed to determine whether
chromoendoscopy might improve
detection and resection of proximal
serrated neoplasia. 741 participants
who had a positive faecal occult
blood test were randomly assigned to
standard white light colonoscopy or
chromoendoscopy. Proximal serrated
polyps were detected in 45 (12%)
of 381 participants who underwent
chromoendscopy compared with
23 (6%) of 360 who underwent
standard white light colonoscopy
(odds ratio 1·96, 95% CI 1·16–3·32;
p=0·012). Although chromoendscopy
took longer to perform, serious
adverse reactions, bowel preparation
scores, completion rates, endoscopist
assessment of procedural difficulties,
procedure comfort scores, technical
quality indicators, and sedation use
were similar with each technique.
Diagnosis of IBS
Diagnosis of IBS is based on
symptoms and negative test results
for other conditions (eg, infections,
coeliac disease, inflammatory
bowel disease, and malignancy).
Barry Marshall (Crawley, WA, Australia)
and colleagues presented findings
from a case-control diagnostic study
in which bowel sounds were used
to characterise individuals with IBS.
Bowel sounds were recorded for 2 h
post-fasting, and then for 40 min after
a standardised meal in 31 participants
with IBS and 37 healthy individuals.
Using computer-based analysis
and modelling, leave-one-out
cross-validation of the model
developed in these individuals showed
90% sensitivity and 92% specificity for
a diagnosis of IBS. Independent testing
in a further 15 participants with IBS
and 15 healthy individuals showed
87% sensitivity and 87% specificity.
These preliminary results suggest that
bowel sounds analysis could be used
in addition to the Rome IV criteria to
assist clinicians in the diagnosis of IBS.
Microbiome treatment for
ulcerative colitis
Misra Bharat (Jacksonville, FL, USA)
and colleagues presented data
from a phase 1b trial of SER-287,
an investigational microbiome
therapeutic, for patients with
ulcerative colitis. 58 patients with
mild-to-moderate ulcerative colitis
were randomly assigned to treatment
or placebo. In two groups, patients
received 6 days of vancomycin
followed by 8 weeks of SER-287 either
daily (n=15) or weekly (n=17). A third
group received placebo pre-treatment
followed by weekly SER-287 (n=15),
and a control group received placebo
throughout the study (n=11).
Remission—defined as a total modified
Mayo score of 2 or less and an
endoscopic subscore of 1 or less—was
noted in six (40%) participants who
received vancomycin pre-treatment
then daily SER-287, compared with
none of the participants who received
placebo (p=0·024). Remission was
noted in two (13%) of participants
who received placebo then SER-287
weekly, and in three (18%) of
those who received vancomycin
then SER-287 weekly. Endoscopic
improvements were also noted with
SER-287. The safety of SER-287 was
similar to placebo; gastrointestinal
adverse events were the most
frequent, but the vancomycin followed
by once-daily SER-287 exhibited the
lowest percentage of such events.
Jennifer Thorley, Rob Brierley