Disease duration did not influence the rates of loss of efficacy of the anti-TNF therapy in Latin American Crohn's disease patients.
Kotze PG, Ludvig JC, Teixeira FV, et al.
BACKGROUND/AIMS: The efficacy of both Infliximab (IFX) and Adalimumab (ADA) can be reduced over time. The aim of this study was to analyze the incidence of loss of efficacy (LOE) of both IFX and ADA, and outline the influence of disease duration on its occurrence.
METHODS: Retrospective, multicenter, observational cohort study, with CD patients treated with anti-TNF therapy. LOE was defined as the need for steroids, occurrence of major abdominal surgery during treatment, dose increase, interval shortening or switching of the anti- TNF agent. Patients were allocated in three subgroups based on disease duration (DD): '24 months, between 24 and 60 months and '60 months.
RESULTS: 175 patients were included in the study (117 under IFX and 58 under ADA therapy). LOE occurred in 32% of patients with DD <24 months="" in="" 33="" 3="" with="" dd="" between="" 24="" and="" 60="" 31="" of="" subjects="" over="" p="0.975)." br=""> CONCLUSIONS: Disease duration (DD) did not influence LOE rates. These results suggest that in real-world observational practice, patients with early CD might have the same rates of LOE than patients with a disease prolonging for a longer duration.
Inflamm Bowel Dis. 2015 Sep 29.
Anti-tumor necrosis factor-α antibody therapy management before and after intestinal surgery for inflammatory bowel disease: a CCFA position paper.
Holubar SD, Holder-Murray J, Flasar M, et al.
Biologic therapy with anti-tumor necrosis factor (TNF)-α antibody medications has become part of the standard of care for medical therapy for patients with inflammatory bowel disease and may help to avoid surgery in some. However, many of these patients will still require surgical intervention in the form of bowel resection and anastomosis or ostomy formation for the treatment of their disease. Postsurgical studies suggest up to 30% of patients with inflammatory bowel disease may be on or have used anti-TNF-α antibody medications for disease management preoperatively. Significant controversy exists regarding the potential deleterious impact of these medications on the outcomes of surgery, specifically overall and/or infectious complications. In this position statement, we systematically reviewed the literature regarding the potential risk of anti-TNF-α antibody use in the perioperative period, offer recommendations based both on the best-available evidence and expert opinion on the use and timing of anti-TNF-α antibody therapy in the perioperative period, and discuss whether or not the presence of these medications should lead to an alteration in surgical technique such as temporary stoma formation.
J Crohns Colitis. 2015 Oct 4.
Mucosal healing in ulcerative colitis - when zero is better.
Boal Carvalho P, Dias de Castro F, Rosa B, et al.
BACKGROUND AND AIMS: Extensive evidence has underlined the importance of mucosal healing as a treatment aim for ulcerative colitis (UC). We aimed to assess differences in the incidence of clinical relapse at 12 months between UC patients with Mayo endoscopic scores (MES) 0 and 1.
METHODS: Retrospective study, including consecutive patients in corticosteroid-free remission between 2008 and 2013 and follow-up of at least one year, with MES 0 or 1 in complete colonoscopy. Clinical relapse was defined as need for induction treatment, treatment escalation, hospitalization or surgery. A p value < 0,05 was considered statistically significant.
RESULTS: Included 138 patients, 72 (52,2%) female, with mean age 49 (±14) years. Inflammatory activity was classified as MES 0 in 61 (44,2%) patients and MES 1 in 77 (55,8%) patients. Clinical relapse during follow-up was significantly more frequent in patients with MES 1 than MES 0 (27,3 versus 11,5%; p=0,022), and in the multivariate analysis, MES 1 was the only factor significantly associated with an increased risk of relapse (OR=2,89 CI 95% 1,14-7,36; p=0,026). This association was encountered in the subgroup of patients with left-sided/extensive colitis (29,7 versus 11,1%; p=0,049), but not proctitis (25,0% versus 12,0%, p=0,202).
CONCLUSIONS: In patients with ulcerative colitis in corticosteroid-free remission, particularly those with left sided colitis or extensive colitis, MES 1 was significantly associated with a threefold increased risk of relapse compared to endoscopic MES 0. Our results support the use of endoscopic MES 0 as the most suitable treatment endpoint to define mucosal healing in patients with UC.
J Crohns Colitis. 2015 Sep 20.
Efficacy and safety of adalimumab in ulcerative colitis refractory to conventional therapy in routine clinical practice.
Bálint A, Farkas K, Palatka K, et al.
BACKGROUND AND AIM: Adalimumab [ADA] was approved for the treatment of ulcerative colitis [UC] refractory to conventional therapy in 2012 in Europe. Due to the observed discrepancies between clinical trials and practice, data on the outcome of ADA therapy are really needed from the real life. The aim of this study was to estimate the short- and long-term efficacy and safety of ADA in UC patients from each Hungarian biological centre.
PATIENTS AND METHODS: This prospective study consisted of UC patients treated with ADA in 10 Hungarian inflammatory bowel disease centres. The primary endpoints of the study were rates of continuous clinical response, remission, non-response and loss of response at Weeks 12, 30, and 52.The secondary endpoints included mucosal healing at Week 52 and the comparison of the efficacy of ADA between biological naive and infliximab [IFX]-treated groups. Colonoscopy was performed before starting the therapy and at Week 52.
RESULTS: In all, 73 active UC patients were enrolled in the study: 67.1% of the patients received previous IFX therapy; 75.3% of the patients showed short-term clinical response at Week 12. The probability of maintaining ADA was 48.6% at Week 52 with a continuous clinical response in 92% of these remaining patients. Mucosal healing was achieved in 48.1% of the patients at Week 52. Escalation of ADA was performed in 17.6%, and minor side effects developed in 4% of the patients; 5.4% of the patients underwent colectomy during the 1-year treatment period.
CONCLUSION: UC is a progressive disease that may need early aggressive therapy to prevent structural and functional complications. The results of our study demonstrated the favourable efficacy of short- and long-term ADA treatment for patients with UC.
World J Gastroenterol. 2015 Oct 7;21(37):10654-61.
Histological healing after infliximab induction therapy in children with ulcerative colitis.
Wiernicka A, Szymanska S, Cielecka-Kuszyk J, et al.
AIM: To verify the impact of induction therapy with infliximab (IFX) on mucosal healing in children with ulcerative colitis (UC).
METHODS: The study included all UC pediatric patients treated with IFX at our center over the last 10 years. The data were collected from patients' medical charts and analyzed retrospectively. A total of 16 patients with UC underwent colonoscopy with sample collection before and after three IFX injections. Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to assess the clinical condition; endoscopic features were classified according to the Baron scale; and histological changes were evaluated according to the protocol of The British Society of Gastroenterology and Geboes Index. Clinical response was defined as a ≥ 20-point reduction in PUCAI index, and clinical remission as PUCAI index < 10 points. Endoscopic mucosal remission was defined as completely normal (score 0) on the Baron scale. Histological remission was defined as grade 0 in the Geboes Index. To assess correlation between variables, Spearman's rank correlation coefficient was used.
RESULTS: Clinical remission (PUCAI < 10) at week 8 was achieved in 68.75% of investigated subjects. Endoscopic mucosal remission at week 8 (Baron 0) was observed in 12.5% of patients. Histological remission (Geboes 0) after induction therapy with IFX was noticed in 18.75% cases. A general histological improvement, expressed by normal surface and crypt architecture, number of crypts, and lamina propria cellularity, was observed in six (37.5%) patients; there was no improvement in nine (56.25%) individuals, and worsening was observed in one (3.75%) case. Changes were not related to UC location. A reduction of inflammatory process was observed in 10 (62.5%) patients; there were no changes in four (25%) individuals, and the inflammation became more severe in two (12.5 %) cases. Simultaneous clinical, endoscopic and histological improvement of parameters assessing disease activity at week 8 was noticed in six (37.5%) patients. 55.5% of investigated patients with normal mucosa seen on endoscopy showed no inflammation on histology. A Baron score of 2 and 3 showed a good correlation with histology results (78.2% of patients with a Geboes Index ≥ 3).
CONCLUSION: IFX has a positive histological effect in more than one-third of UC patients. IFX reduces intestinal inflammation and improves clinical condition.
Gut. 2015 Oct 16.
Development and validation of a histological index for UC.
Mosli MH, Feagan BG, Zou G, et al.
OBJECTIVE: Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument.
DESIGN: Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatt's responsiveness statistic (GRS) using data from a clinical trial of an effective therapy.
RESULTS: Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively.
CONCLUSIONS: The RHI is a new histopathological index with favourable operating properties
Gut. 2015 Oct 13.
Development and validation of the Nancy histological index for UC.
Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al.
OBJECTIVE: We developed a validated index for assessing histological disease activity in UC and established its responsiveness.
METHODS: Two hundred biopsies were scored. The outcome was the Global Visual Evaluation (GVE). Eight histological features were tested. The Nancy index was developed by multiple linear regression and bootstrap process to create an index that best matched the GVE. Goodness of fit was assessed by the adjusted R squared (adjusted R2). The second step was the validation of the index: 100 biopsies were scored for the Nancy index by three pathologists from different centres. Inter-reader reliability was evaluated for each reader. The relationship between the change of the Nancy index and the Geboes index was assessed to assess the responsiveness.
RESULTS: After backward selection with bootstrap validation, 3/8 items were selected: ulceration (adjusted R2=0.55), acute inflammatory infiltrate (adjusted R2=0.88) and chronic inflammatory infiltrate (adjusted R2=0.79). The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.88 (95% CI 0.82 to 0.92) and the index had good inter-reader reliability (ICC=0.86 (0.81 to 0.99)). The correlation between the Nancy index and the Geboes score or the GVE was very good. The index had a good responsiveness with a high correlation between changes in the Geboes score and changes in the Nancy index (0.910 (0.813 to 0.955)).
CONCLUSIONS: A three descriptor histological index has been validated for use in clinical practice and clinical trials.
Rheumatology (Oxford). 2015 Nov;54(11):1941-3.
Measurement of anti-drug antibodies to biologic drugs.
Felis-Giemza A, Moots RJ.
No abstract available.