Introduction

While randomized studies have shown that Amgevita (an adalimumab biosimilar) and Humira (adalimumab originator) are equivalent, concerns persist among patients and prescribers as to its efficacy. Patients switching to a medicine they perceive as lower cost may experience a ‘nocebo’ effect, whereby expectations of poorer efficacy may lead to worse clinical outcomes, resulting in an unmeasured health economic burden.

Aims & Methods

70 patients partook in a biosimilar switch study at our centre in August 2020, undergoing a change in treatment from Humira to Amgevita. Baseline clinical data obtained included faecal calprotectin, drug and drug antibody levels, Harvey-Bradshaw (HBI) and Partial-Mayo scores. Patient-Reported Outcomes (PROs) were recorded through the IBD control-8 (IBDC8) and IBCD visual analogue scale (IBDQ-VAS). Patients took psychometric tests 8 weeks pre-switch, including the ‘Beliefs about Medicines’ questionnaire (BMQ), used to assess beliefs about prescribed medications, the ‘Health Anxiety Index’ (HAI), used to identify patients with high levels of concern about their health, and the EQ-5D questionnaire, used to measure health-related quality of life. The original study found no significant differences in clinical and PROs at 8-week follow-up. We planned to conduct a 32-month follow-up on these patients to examine for temporal changes in outcomes, and whether certain variables could predict the patients experiencing a ‘nocebo’ effect. Approval was obtained from the hospital ethics committee. Patient information from the original study was stored on an excel database. We retrospectively obtained clinical data from electronic records and lab data. Questionnaire results were obtained from clinic appointments.

Results

70 patients were included in the study. 41 male, 29 female. 54 patients had Crohn’s, 13 UC, and 4 indeterminate colitis. 25.7% of patients reported adverse events post-switch, with 33.3% of these patients switching back to Humira. The most common side effects were skin related (8.6%), injection site related (5.7%), and headaches (2.8%). 8.6% of patients felt the medication to be less effective without specific symptoms. 32-months post switch, 72.7% remained on Amjevita, 9.1% had switched back to Humira, 7.6% had switched to another biologic as clinical non-responders, 10.6% had stopped biologic treatment due to surgery or clinical remission.
Median scores were calculated at 8 weeks pre and post-switch, and at 32 months. HBI scores were 2, 1 and 1 respectively, with scores of 1, 0 and 0 in the switchback group. IBDC8 scores were 12, 13 and 14 overall, with scores of 12, 10 and 14 in the switchback group. IBDQ-VAS scores were 87, 80 and 90 overall, with scores of 100, 100 and 85 in the switchback group. Median HAI scores were lower in the switchback group; scoring 12 versus 17 overall. Median scores in four domains of the BMQ questionnaire; general harm, general overuse, specific concerns and specific necessity were lower in the switchback group. Scores were 12, 12, 8, 7, versus overall scores of 21, 14, 10, and 9 respectively, indicating more negative attitudes towards medicines in the switchback group.

Conclusion

Our study found no negative impact in clinical outcomes and PROs in patients switching from Humira to Amgevita at 32-months post-switch. Patients that had more negative attitudes to medicines in the BMQ questionnaire were more likely to switchback to Humira suggesting a nocebo effect. Enhanced patient education may help mitigate the nocebo effect observed in our study and enhance the success rate of future biosimilar switch trials.

Introduction

In Crohn’s disease (CD) a symptomatic luminal stricture occurs in up to 20% of patients at the diagnosis and in more than 50% during lifetime (1,2). Endoscopic balloon dilatation (EBD) or surgical procedures are the currently available treatments (3,4). However, a considerable percentage of patients often require further surgery for post-operative CD recurrence (5). A consequent increased burden of short bowel syndrome is warranted. The combination of biological therapy with EBD could potentially reduce this risk.

Aims & Methods

The aim of our study was to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD’s patients. We conducted a retrospective study including consecutive CD patients who underwent EBD for low bowel strictures from December 2015 until November 2022 at our tertiary IBD Center. Clinical strictures recurrence, needs for steroids and for surgery due to CD stenosis relapse were the primary outcomes evaluated during a follow-up period of six and twelve months. Chi-square and univariate statistical analyses were used when appropriate.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. In the study population, 14 patients (27%) were smoker, the mean age was of 46,8 (18-77) years; the median of disease duration was 9 (0-42) years. Thirty-nine patients (75%) were in active treatment with biologic therapy at the moment of EBD. Twenty-three patients (44%) underwent EBD for anastomotic stricture, 8 (15%) for ileal stricture, 11 (21%) for ileocecal valve stricture, 5 (6%) for anal stricture and 4 (8%) for colic stricture. Three patients (6%) underwent EBD for multifocal bowel stenosis. Twenty-two (42%) patients had increased CRP value, 40 patients (77%) had evidence of moderate or severe endoscopic disease activity and 42 (81%) patients showed ulcerative lesions at stricture site. EBD was performed by 8-10, 12-15 or 15-18 mm dilation balloon. Technical success was reported in 60% of procedures and no adverse events were registered.
After 6 months from EBD, at univariate analysis, active smoke resulted a risk factor for clinical stricture recurrence (OR 10,25; IC 1,350 to 135,4; p value = 0,022) and for subsequent surgery (OR 10,25; IC 1,350 to 135,4; p value = 0,022). Moreover, increased CRP at the time of dilatation resulted a risk factor for need of steroids (OR 14,63; IC 2,69 to 71,50; p value = 0,0006). Concomitant biologic therapy and presence of ulcerative lesions did not show significative correlation with considered outcomes.
After 12 months from EBD, concomitant biologic therapy resulted a protective factor for prevention of surgery (OR 0,061; IC 0,005 to 0,502; p value = 0,0047), while anastomotic strictures were associated with a lower risk of sub-occlusion events than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p value = 0,015). Increased CRP at the time of EBD, ulcerative lesions at the stricture site and active smoke were not significantly correlated with the considered outcome.

Conclusion

Our results suggest that in patients with CD undergoing EBD for bowel CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

References

1. Rieder F Managing Intestinal Fibrosis in Patients With Inflammatory Bowel Disease. Gastroenterology & hepatology. 2018. February; 14(2):120–122
2. Yoo JH, Holubar S, Rieder F. Fibrostenotic strictures in Crohn’s disease. Intest Res. 2020;0.
3. Paine E, Shen B. Endoscopic therapy in inflammatory bowel diseases (with videos). Gastrointest Endosc 2013;78:819–35.
4. Hassan C, Zullo A, De Francesco V, Ierardi E, Giustini M, Pitidis A, Taggi F, Winn S, Morini S. Systematic review:
Endoscopic dilatation in Crohn's disease. Aliment Pharmacol Ther. 2007 Dec;26(11-12):1457-64
5. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms. Gut 1992;33:331–5.

Introduction

​The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs.

Aims & Methods

​In this single-center phase II pilot study (ClinicalTrials.gov ID: NCT05750030), we plan to include 12 patients with advanced HCC who progressed on atezolizumab/bevacizumab. Patients will receive atezolizumab/bevacizumab every 3 weeks in combination with a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events (TRAEs). The main secondary endpoint is best overall response (BOR) according to RECISTv1.1 and mRECIST. Here, we report results of a preplanned interim analysis.

Results

Of 6 patients included so far, 5 were male, 5 had BCLC stage C, and 5 had Child-Pugh class A. All patients underwent successful FMT without any periinterventional complications. TRAEs related to FMT were all low-grade (grade 1-2) and included bloating (n=2), constipation (n=2), and diarrhea (n=1). TRAEs related to atezolizumab included one grade 2 pruritus, and TRAEs related to bevacizumab included arterial hypertension (one grade 3 and two grade 2) and proteinuria (one grade 3 and one grade 1). All patients had at least one follow-up imaging. Two patients had partial response, 3 patients had stable disease, and 1 patient had progressive disease as BOR according to both RECISTv1.1 and mRECIST, which corresponds to an objective response rate of 33% and a disease control rate of 83%.

Conclusion

Based on acceptable safety and promising efficacy results, the decision to continue recruitment in this trial was made. An update with longer follow-up will be presented at the meeting, including analyses of the gut microbiome.

Disclosure

AF received travel support from Takeda and Amgen, he received speaker honoraria from AbbVie
KP has nothing to disclose.
BS received travel support from AbbVie, AstraZeneca, Gilead and Ipsen, speaker honoraria from Eisai as well as grant support from AstraZeneca and Eisai.
BL received speaker honoraria from Chiesi and Gilead.
LP has nothing to disclose.
AK has nothing to disclose.
KR has nothing to disclose.
KZ has nothing to disclose.
MT received speaker honoraria from Albireo, BMS, Falk Foundation, Gilead, Intercept, Madrigal and MSD; he has advised for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk Pharma GmbH, Genfit, Gilead, Hightde, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Rectify Regulus, Siemens and Shire. He further received travel grants from Abbvie, Falk, Gilead Intercept and Jannsen and research grants from Albireo, Almylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and Ultragenyx. He is also co-inventor of patents on the medical use of NorUDCA filed by the Medical Universities of Graz and Vienna.
DT served as a speaker and/or consultant and/or advisory board member for Siemens, Roche, Sanova, Bristol-Myers Squibb and received travel support from Bayer and Siemens.
CG nothing to disclose.
MP received speaker honoraria from Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he is a consultant/advisory board member for AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he received grants from AstraZeneca, Bayer, BMS, and Roche; he received travel support from Bayer, BMS, Ipsen, and Roche.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive endoscopic procedure that is crucial for pancreato-biliary diseases and selective cannulation is the most important step. However, even an experienced endoscopist can face cannulation failure in up to 15-30% of cases in the first ERCP when standard methods alone are used.¹ Many studies suggested the various needle knife fistulotomy or papillotomy as an alternative technique in difficult cannulation cases.^2,3 However, needle knife papillotomy (NKP), which is modified technique with needle knife has not been evaluated well.

Aims & Methods

To evaluate the clinical outcomes and adverse events of bile duct cannulation by NKP, we performed a retrospective review on medical records of all ERCP cases in Sheikh Khalfia Specialty Hospital, UAE. For six years, Sphincterotomy (SPT) naïve patients except altered-anatomy cases were enrolled and their procedure times, cannulation success rates, radiation exposures, and adverse events were measured between the procedure time matched two cohort group of SPT only and rescue NKP.

Results

In total 416 ERCP cases, 43 procedure time matched cases were selected among 352 (84.7%) SPT only cohort and 43 cases from 64 rescue NKP cohort. Biliary cannulation was succeeded in all cases (100%) by using SPT cannulation with rescue NKP technique without failure. There was no differences in cumulative radiation doses, cannulation time, and adverse event rates in rescue NKP group compared to SPT only group: Post-ERCP hyperamylasemia/hyperlipasemia (16.5% vs. 34.8%, p=0.080), pancreatitis (3.9% vs. 4.3%, p=0.883), cholangitis (4.7% vs. 4.3%, p=0.695), and no perforation case was noticed in both groups.

Conclusion

The SPT with rescue NKP technique can be used in the difficult biliary cannulation cases during ERCP safely and effectively.

References

(1) Testoni PA , Testoni S , Giussani A .
Difficult biliary cannulation during ERCP: how to facilitate biliary access and minimize the risk of post-ERCP pancreatitis.
Dig Liver Dis 2011;43:596–603
[2] Testoni PA , Mariani A , Aabakken L , Arvanitakis M , Bories E , Costamagna G,et al.
Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
Endoscopy 2016;4 8:657–6 83 .
[3] Lopes L , Dinis-Ribeiro M , Rolanda C .
Early precut fistulotomy for biliary access: time to change the paradigm of "the later, the better"?
Gastrointest Endosc 2014;80:634–641 .