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Digestive Disease Week 2018


Subcutaneous biosimilars titrated up to 100 mg at bedtime no serious adverse events or safety
A novel subcutaneous formulation for baclofen failures; n=25), or signals in the study.
of the infliximab biosimilar CT-P13 placebo medical treatment (active Christophe Cellier (Paris, France)
might be a more convenient option omeprazole 20 mg twice daily with and colleagues also presented results
for patients with Crohn’s disease, if placebo baclofen and desipramine; from a phase 2A, double-blind,
results presented by Stefan Schreiber n=26). The primary outcome— placebo-controlled trial of AMG 714 in
(Kiel, Germany) and colleagues are success rate at 12 months, defined as patients with refractory coeliac disease
confirmed in an ongoing formal 50% or greater improvement in the type II (also known as pre-enteropathy-
efficacy trial. 44 patients with active GERD-heath-related quality of life associated T-cell lymphoma), a
Crohn’s disease were treated with score—was achieved by 18 (67%) in rare small bowel lymphoma that
intravenous CT-P13 at weeks 0 and 2, the surgical group, seven (28%) in the primarily arises as a complication of
and at week 6 were randomly assigned active medical group, and three (12%) coeliac disease. Patients (n=28) were
to one of four cohorts—one with in the placebo group (p=0·007 for randomly assigned (2:1) to receive Published Online
continued dosing of intravenous surgery vs medical treatment and 8 mg/kg of AMG 714 or matching June 13, 2018
http://dx.doi.org/10.1016/
CT-P13, or one of three different doses p<0·0001 for surgery vs placebo). placebo (seven intravenous doses S2468-1253(18)30202-4
of subcutaneous CT-P13. All patients Serious adverse events occurred in over 10 weeks). The primary endpoint Digestive Disease Week 2018
received treatment for 30 weeks. four patients in the surgical group, of reduction in intestinal aberrant took place in Washington, DC,
Efficacy measures—including change four in the active medical treatment intra-epithelial lymphocytes did not USA, on June 2–5, 2018

from baseline in the Crohn’s disease group, and three in the placebo group. differ significantly between groups,
activity index and clinical remission— but AMG 714 was associated with
were similar in those receiving AMG 714 for coeliac disease interruption in disease progression and
subcutaneous CT-P13 compared Markku Maki (Tampere, Finland) and improvement in symptoms. Six serious
to those with intravenous CT-P13, colleagues presented the results of a adverse events were reported (five in
as were safety profiles. A lower phase 2A, double-blind, randomised the AMG 714 group and one in the
proportion of patients were positive controlled trial of AMG 714, an anti- placebo group); mild nasopharyngitis
for anti-drug antibodies following interleukin-15 monoclonal antibody, was the most common adverse
treatment with subcutaneous CT-P13 for amelioration of the effects of reaction in the AMG 714 group.
than with the intravenous form­ gluten consumption in patients
ulation. Pharmacokinetic and pharma­ with coeliac disease. Patients were Mirikizumab for ulcerative
codynamic modelling suggested randomly assigned (1:1:1) to receive colitis
that subcutaneous and intravenous 150 mg AMG 714, 300 mg AMG 714, The pro-inflammatory cytokine
formulations were similar in patients or placebo in six subcutaneous doses interleukin 23 is involved in inflam­­
with active Crohn’s disease. over 10 weeks. Between weeks 2 and matory bowel disease patho­
12, patients received a high-dose genesis, and blockade of the
PPI-refractory heartburn gluten challenge of around 2·5 g per interleukin-23 pathway has been
Up to 40% of patients with gastro- day (n=49), except for those who had shown to have efficacy in Crohn’s
oesophageal reflux disease treated mucosal atrophy at baseline (n=11). disease. In a multicentre, phase 2,
with proton pump inhibitors The primary outcome—change in double-blind, placebo-controlled
(PPIs) continue to have symptoms. villous height to crypt depth ratio— trial, William Sandborn (San Diego,
Stuart Spechler (Dallas, TX, USA) among those who underwent gluten CA, USA) and colleagues assessed the
and colleagues presented the results challenge was –61% in the placebo safety and efficacy of mirikizumab,
of a randomised trial comparing group, –62% in the 150 mg AMG 714 an anti-interleukin-23 antibody, for
medical and surgical treatments for group, and –55% in the 300 mg group treatment of moderate-to-severe
patients with gastro-oesophageal (–16%, –6% and –3%, respectively, for ulcerative colitis. Patients were
reflux disease refractory to PPIs. those who did not undergo gluten randomly assigned (1:1:1:1) to receive
Patients (n=78) were randomly challenge); there was no significant placebo (n=63), 50 mg (n=63) or
assigned to receive surgical treatment difference between groups. The 200 mg (n=62) mirikizumab with a
(laparoscopic Nissen fundoplication; 300 mg group reported significant possibility of exposure-based increases,
n=27), active medical treatment improvement in the Celiac Disease or fixed-dose 600 mg mirikizumab
(omeprazole 20 mg twice daily plus Patient-Reported Outcome score (n=61) intravenously at weeks 0, 4, and
baclofen titrated up to 20 mg three (p=0·02), and the Physician Global 8. At week 12, the clinical remission
times daily, followed by desipramine Assessment score (p=0·01). There were rate (the primary outcome) was

www.thelancet.com/gastrohep Vol 3 August 2018 531


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significantly greater in the mirikizumab of overall IBS symptoms (and Using computer-based analysis
200 mg group (23%; p<0·01), but not abdominal bloating in particular) and modelling, leave-one-out
in the 50 mg (16%) or 600 mg groups 12 weeks after transplantation—was cross-validation of the model
(12%), than in the placebo group (5%). achieved in 49% in the FMT group developed in these individuals showed
Rates of serious adverse events and versus 29% in the placebo group 90% sensitivity and 92% specificity for
treatment-emergent adverse events (p=0·004). There were no significant a diagnosis of IBS. Independent testing
were similar across treatment groups. differences in efficacy between donors. in a further 15 participants with IBS
and 15 healthy individuals showed
Low-volume bowel preparation Screening for serrated polyps 87% sensitivity and 87% specificity.
A ready-to-drink, low-volume bowel Serrated lesions are often precursors to These preliminary results suggest that
preparation of a split-dose oral sodium post-colonoscopy interval colorectal bowel sounds analysis could be used
picosulfate, magnesium oxide, and cancers, and are considered difficult to in addition to the Rome IV criteria to
citric acid solution was non-inferior detect. Sunil Dolwani (Cardiff, UK) and assist clinicians in the diagnosis of IBS.
to a split-dose powder solution, colleagues presented findings from
according to a phase 3 trial presented the Bowel Screening Wales colorectal Microbiome treatment for
by Lawrence Hookey (Kingston, cancer screening programme, ulcerative colitis
ON, Canada) and colleagues. designed to determine whether Misra Bharat (Jacksonville, FL, USA)
901 participants were randomly chromoendoscopy might improve and colleagues presented data
assigned to receive either the oral detection and resection of proximal from a phase 1b trial of SER-287,
solution (n=448) or the powder serrated neoplasia. 741 participants an investigational microbiome
(n=453). The primary endpoint— who had a positive faecal occult therapeutic, for patients with
the proportion of participants with blood test were randomly assigned to ulcerative colitis. 58 patients with
excellent or good ratings for bowel standard white light colonoscopy or mild-to-moderate ulcerative colitis
cleansing on the Aronchick scale—was chromoendoscopy. Proximal serrated were randomly assigned to treatment
noted in 87·7% (95% CI 84·3–90·6) polyps were detected in 45 (12%) or placebo. In two groups, patients
participants in the oral solution of 381 participants who underwent received 6 days of vancomycin
group and 81·5% (77·6–84·9) in chromoendscopy compared with followed by 8 weeks of SER-287 either
the powder group (difference 6·3%, 23 (6%) of 360 who underwent daily (n=15) or weekly (n=17). A third
95% CI 1·8–10·9; p=0·0067). No standard white light colonoscopy group received placebo pre-treatment
serious treatment-emergent adverse (odds ratio 1·96, 95% CI 1·16–3·32; followed by weekly SER-287 (n=15),
events related to the study treatments p=0·012). Although chromoendscopy and a control group received placebo
were reported, and any adverse took longer to perform, serious throughout the study (n=11).
events possibly related to the study adverse reactions, bowel preparation Remission—defined as a total modified
intervention were reported by 13·2% scores, completion rates, endoscopist Mayo score of 2 or less and an
participants in the oral solution group assessment of procedural difficulties, endoscopic subscore of 1 or less—was
and 16·8% of those in powder group. procedure comfort scores, technical noted in six (40%) participants who
quality indicators, and sedation use received vancomycin pre-treatment
FMT for IBS were similar with each technique. then daily SER-287, compared with
Tom Holvoet (Ghent, Belgium) and none of the participants who received
colleagues reported the results of a Diagnosis of IBS placebo (p=0·024). Remission was
double-blind, placebo-controlled trial of Diagnosis of IBS is based on noted in two (13%) of participants
faecal microbiota transplantation (FMT) symptoms and negative test results who received placebo then SER-287
for irritable bowel syndrome (IBS) with for other conditions (eg, infections, weekly, and in three (18%) of
predominant abdominal bloating. coeliac disease, inflammatory those who received vancomycin
Patients were randomly assigned (2:1) bowel disease, and malignancy). then SER-287 weekly. Endoscopic
to transplantation with fresh donor Barry Marshall (Crawley, WA, Australia) improvements were also noted with
stool (n=42) or with placebo (patient’s and colleagues presented findings SER-287. The safety of SER-287 was
own frozen stool; n=22). Donors (n=2) from a case-control diagnostic study similar to placebo; gastrointestinal
were selected based on having a high in which bowel sounds were used adverse events were the most
microbial richness and yielding good to characterise individuals with IBS. frequent, but the vancomycin followed
clinical results in a preliminary pilot Bowel sounds were recorded for 2 h by once-daily SER-287 exhibited the
trial, and were regularly screened post-fasting, and then for 40 min after lowest percentage of such events.
for infectious diseases. The primary a standardised meal in 31 participants
outcome—self-reported improvement with IBS and 37 healthy individuals. Jennifer Thorley, Rob Brierley

532 www.thelancet.com/gastrohep Vol 3 August 2018