Abstract
Background
Several adalimumab preparations are now available on the market for patients with inflammatory bowel disease. Comparative satisfaction and tolerability are unknown. The aim of ...this study was to investigate inflammatory bowel disease patient satisfaction with approved adalimumab biosimilars and their originator.
Methods
In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with inflammatory bowel disease across 45 centres affiliated with the GETAID who completed a satisfaction questionnaire comprising four items each rated by a 10 points-scale. The differences in responses were performed using one-way analysis of variance followed by Tukey's Honest Significant Difference test.
Results
The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%), and Hulio® (105/941, 11.2%). Mean overall satisfaction rate with adalimumab was 8.5 standard deviation 1.8. Overall satisfaction was significantly higher in patients treated with Humira® (8.6 1.5), Hulio® (8.6 1.8) or Amgevita® (8.5 1.4) (p<0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 1.4), Humira® (8.9 1.3) and Hulio® (8.9 1.7) (p<0.05). A total of 299 patients (31.8%) described injection site reactions. Two hundred twenty-three patients (23.7%) reported that they were previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects.
Conclusion
In this real-world setting, patients with inflammatory bowel disease had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.
Abstract
Background
Achieving deep and continuous remission with tight control could allow de-escalation in patients with UC. The in-TARGET study was a prospective two-phase trial in UC patients ...initiating golimumab (GLM), that aimed to determine the proportion of patients with continuous clinical response (CCR) and endoscopic remission (ER) after one year of treatment optimization strategy (phase 1); then to assess treatment de-escalation outcome in these patients (phase 2).
Methods
This was a multicentre prospective interventional study in GETAID centres. The study included adult patients with active UC (Mayo Score ≥6 with an endoscopic subscore ≥2), naive to biologics. In the first part of the study, patients received a conventional GLM regimen, depending on their weight (<80 kg; ≥80 kg). At week 10, primary responders continued with the standard maintenance regimen (50 mg or 100 mg/4 w) and non-primary responders had systematic treatment optimization (<80 kg, GLM 100mg/4 w; ≥80kg, introduction of an immunosuppressant) (Figure 1). In the second part of the study, patients in CCR and in ER (Mayo endoscopic score 0-1) at w 54, had treatment de-escalation: GLM discontinuation for patients receiving 50mg, and dose de-escalation to 50mg for those receiving 100mg.
Results
A total of 197 patients were included, mean duration of UC was 75.9 (± 95.3) months, the mean total Mayo score was 8.4 (± 1.7). At w 10, 14 patients had stopped treatment for failure, 83 (42.1%) had a primary response, and 100 (50.7%) non-primary responders had treatment optimization. At w 54, 95 (48.2%) patients were still on GLM; of these, 64 (32.5%) patients were in CCR and ER. At w 0 and 10, no factors were associated with CCR + ER at w54. Serum GLM levels after w10 were not associated with CCR and ER at w54. No patient developed anti-GLM antibodies between w0 and w54.
Sixty patients participated in the second de-escalation phase of the study: in 18 GLM was discontinued, in 38 GLM dose was de-escalated from 100 to 50mg/4 w, and 4 patients refused dose de-escalation. At w 108, 34/56 (60.7%) patients were in CCR and ER, with no change in treatment. No factors were associated with w108 remission. At w108, 23 patients had relapsed: 4/18 (22.2%) among GLM discontinuations, 19/38 (50%) among patients de-escalated from 100 to 50 mg/4w.
During follow-up, no colectomy was reported, and 14 severe non-UC related adverse events occurred (3 severe infections, 2 severe anaemias, and 1 rectal cancer).
Conclusion
One third of UC patients achieved a CCR with ER at one year with optimized GLM therapy. After de-escalation of GLM, 60% of remitters at one year maintained deep remission at two years. Anti-TNF de-escalation following a treat-to-target strategy could be considered in some UC patients.
Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, ...colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX.
This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed.
A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy.
In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.
Background and aims: Following ileocolonic resection for Crohn’s disease (CD), early endoscopic recurrence predicts recurrence of symptoms. The aim of the study was to compare ileocolonoscopy and ...wireless capsule endoscopy (WCE) for the detection of postoperative recurrence in CD. Methods: WCE and ileocolonoscopy were performed within six months following surgery in 32 prospectively enrolled patients. Two independent observers interpreted the results of WCE. Recurrence in the neoterminal ileum was defined by a Rutgeerts score ⩾1. When observers at WCE did not concur, WCE results were considered as either true negative or true positive and sensitivity and specificity were calculated according to both assumptions. Results: Recurrence occurred in 21 patients (68%) and was detected by ileocolonoscopy in 19 patients. Sensitivity was 90% and specificity 100%. Sensitivity of WCE was 62% and 76% and specificity was 100% and 90%, respectively, depending on assumptions. There was a correlation between the severity of the lesions measured by both methods (p<0.05). Lesions located outside the scope of conventional endoscopy were detected by WCE in two thirds of patients with excellent interobserver agreement (kappa >0.9) for all lesions with the exception of ulceration (kappa = 0.7). Conclusions: The sensitivity of WCE in detecting recurrence in the neoterminal ileum was inferior to that of ileocolonoscopy. In contrast, WCE detected lesions outside the scope of ileocolonoscopy in more than two thirds of patients. Additional follow up studies are needed to assess the clinical relevance of such lesions. At the present time, it seems that WCE cannot systematically replace ileocolonoscopy in the regular management of patients after surgery.
BACKGROUND/AIM Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFκB), which is involved in their gene transcription, is ...increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression. METHODS Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFκB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFκB inhibitory protein (IκBα) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis. RESULTS Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFκB from the cytoplasm to the nucleus. LPS induced NFκB transcriptional activity was decreased by butyrate while IκBα levels were stable. Butyrate treatment also improved TNBS induced colitis. CONCLUSIONS Butyrate decreases proinflammatory cytokine expression via inhibition of NFκB activation and IκBα degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.
Summary
Background The pathogenesis of Crohn’s disease (CD) involved microbial factors. Some Helicobacter species, the so‐called entero‐hepatic Helicobacters (EHH), can naturally colonize the ...intestinal surface and have been detected in humans.
Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies.
Methods Two groups of patients were included prospectively in a multicentre cross‐sectional study: CD patients with an endoscopic post‐operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis.
Results In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age‐adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04–6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis.
Conclusion Crohn’s disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.
Aliment Pharmacol Ther 31, 1178–1185
Summary
Background Efficacy of infliximab in treating ulcerative proctitis remains unknown.
Aim To evaluate the clinical, biological and endoscopic efficacy of ...infliximab therapy in refractory proctitis.
Methods The charts of 420 patients treated with infliximab for ulcerative colitis were reviewed. Thirteen patients were treated with infliximab for refractory ulcerative proctitis in six referral centres between 2005 and 2009.
Results Following infliximab therapy induction, 9/13 patients (69%) had a complete response (defined as absence of diarrhoea and blood), 2/13 (15%) had a partial response and 2/13 (15%) were primary nonresponders. The median follow‐up was 17 months (range, 3–48). Among the 11 patients with clinical response after infliximab induction therapy, 9 (82%) patients maintained response at last follow‐up. Disappearance of rectal disorders was observed in all nine patients who maintained clinical response at last follow‐up. Following infliximab induction therapy, the mean CRP level fell from 12.8 mg/L to 4.7 mg/L. Endoscopic evaluation was performed before and after infliximab in seven patients, showing an improvement in mucosal lesions in four patients, persistent mild endoscopic activity in two patients and no improvement in one patient. One patient underwent proctocolectomy.
Conclusion Infliximab therapy seems to be effective in inducing and maintaining a clinical response in refractory ulcerative proctitis.
Confocal laser endomicroscopy (CLE) might discriminate mucosal lesions between Crohn’s disease (CD) and ulcerative colitis (UC). However, the analysis of CLE images requires time-consuming methods, a ...long training time, and potential impediments, such as significant interobserver variability. Therefore, we developed a computer-based method to analyze mucosal architecture from CLE images and discriminate between healthy subjects and patients with inflammatory bowel disease (IBD) as well as between UC and CD patients.
We retrospectively screened patients who had undergone CLE either for an evaluation of IBD in remission or for colorectal cancer screening (control subjects) between 2009 and 2016. We assessed 14 morphologic and functional parameters in each CLE recording from 23 CD patients, 27 UC patients, and 9 control patients. Next, we constructed 2 scores, 1 for the IBD diagnosis and 1 for the differential diagnosis between UC and CD.
In IBD patients, the mean intercrypt distance, wall thickness, and fluorescein leakage through the colonic mucosa were significantly increased compared with control patients by 155%, 188%, and 297%, respectively (P < .05). In UC patients, the same parameters were significantly increased by 109%, 117%, and 174%, respectively (P < .05), compared with CD patients. IBD diagnosis had 100% (95%CI, 93%; 100%) sensitivity and 100% (95%CI, 66%; 100%) specificity. IBD differential diagnosis provided discrimination of UC from CD patients with 92% (95%CI, 75%; 99%) sensitivity and 91% (95%CI, 72%; 99%) specificity.
Confirming these results using prospective validation cohorts can substantiate that computer-based analysis of CLE images may provide new biomarkers for the diagnosis and characterization of IBD.
Abstract Background Despite a growing therapeutic armamentarium, post-operative recurrence (POR) in Crohn’s disease (CD) remains frequent. The presence of myenteric plexitis at the proximal margin of ...ileocolonic resection has been recognized as a risk factor for early POR. They are defined by the accumulation of immune cells in contact with the ganglia of the myenteric plexus. In preliminary work, we have shown an increase in the number of T lymphocytes (TL) in contact with enteric glial cells (EGC) in patients with CD depending on ICAM-1/LFA-1 pathway. As CD is classically associated with a Th1 immune response, the aim of this work was to study the impact of EGC/CD4+ TL contacts on Th1-type cytokine production (IFNγ and its transcription factor Tbet) and to identify molecules that may be involved in these regulations. Methods In vitro in rats, the impact of EGC/CD4+ TL co-culture on IFNγ production was studied by ELISA and qPCR of the transcription factor Tbet. The expression and regulation of PD-L1, a candidate molecule, was then analyzed in murine and human EGC by qPCR and immunohisto/cytochemistry. Results While EGC alone produced only a small amount of IFNγ, there was a significant reduction in IFNγ production in EGC/CD4+ TL co-cultures compared with CD4+ TL alone. Yet the proportion of CD4+ TL cells capable of producing IFNγ was significantly increased in contact with EGC, as was their survival. In parallel, Tbet was downregulated in CD4+ TL in contact with EGC. These results suggested the involvement of PD-L1, a molecule known to negatively regulate cytokine production (notably IFNγ) and Tbet expression. Expression of PD-L1 mRNA and its protein was demonstrated in murine and human EGC and was upregulated under pro-inflammatory conditions. Analysis of transmural sections at the proximal margin of ileocolonic resection from patients (n=15 controls, n=14 CD without POR, n=15 CD with POR) showed PD-L1 expression in myenteric ganglia that was restricted to EGC (no neuronal expression) (Figure 1A). PD-L1 fluorescence intensity in myenteric ganglia at the proximal resection margin was significantly lower in CD patients with POR than in controls (∆13.5%; p=0.012) (Figure 1B). Conclusion Lower IFNγ production in EGC/CD4+ TL co-cultures associated with reduced Tbet expression by TL in contact with EGC suggest a role of PD-L1 in myenteric plexitis. PD-L1 expression has been demonstrated in murine and human EGC, with significantly lower expression in myenteric ganglia located at the proximal resection margin of CD patients with POR compared with controls. Blocking the ICAM-1/LFA-1 pathway and/or restoring the PD-1/PD-L1 loop could be of interest for developing strategies to prevent and/or treat POR in CD patients.
Capsule endoscopy (CE) is a safe, non-invasive diagnostic tool to evaluate small bowel lesions. CE, like conventional endoscopy, can detect focal and small-ulcerated lesions along the entire length ...of the small bowel, which are not identified by other imaging techniques. Meta-analysis has shown that CE is better than any other radiological technique to detect small bowel lesions in patients with suspected or known Crohn's disease (CD). In unclassified colitis, CE is also useful in distinguishing CD and ulcerative colitis (UC). In established CD, CE may be used to detect post-operative recurrence, determine the extent of small bowel lesions and link ulcerated lesions with clinical symptoms. Although CE is well tolerated there is a theoretical risk of capsule impaction in general and in CD in particular. To avoid capsule impaction, a new option called the “patency capsule” is available especially in patients with symptoms suggesting small bowel obstruction. However, few data are available about this new device and its use in clinical practice needs to be clarified.
L’exploration par vidéocapsule endoscopique (VCE) est un outil diagnostique non invasif, sûr, permettant de rechercher des lésions de l’intestin grêle. L’examen par VCE peut détecter des lésions ulcérées de petite taille et de localisation focale, que les techniques d’exploration conventionnelles ne mettent pas en évidence, tout le long de l’intestin grêle. Plusieurs méta-analyses ont montré que la VCE supérieure aux techniques radiologiques pour détecter des lésions de l’intestin grêle dans la maladie de Crohn. Dans les colites indéterminées, l’examen par VCE est également souvent utile pour distinguer maladie de Crohn et rectocolite hémorragique. Dans la maladie de Crohn connue, la VCE est un outil qui permet de recherche une récidive endoscopique postopératoire, de déterminer l’extension de la maladie sur l’intestin grêle, et de relier des symptômes cliniques à l’existence de lésions du grêle. Si l’examen par VCE est habituellement bien toléré, il existe toutefois un risque d’impaction de la capsule, ceci encore d’avantage dans la maladie de Crohn. Pour essayer de diminuer au maximum (idéalement d’éviter) ce risque, une capsule
« patency » est aujourd’hui disponible, d’autant plus utile chez les malades présentant des symptômes qui peuvent suggérer un syndrome sub-occlusif. Néanmoins, peu de données sont actuellement disponible concernant la place exacte de cette capsule
« patency » en pratique quotidienne.
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