Background and Aims Therapeutic drug monitoring [TDM] has proven to be effective for optimising anti-tumour necrosis factor [TNF] therapy in inflammatory bowel disease [IBD]. Nevertheless, the majority of data refer to infliximab and reactive testing or association studies. We aimed to compare the long-term outcome of patients with IBD who received at least one proactive TDM of adalimumab, with standard of care, defined as empirical dose escalation and/or reactive TDM. Methods This was a multicentre retrospective cohort study. Patients on maintenance adalimumab therapy from June 2006 to December 2015 were eligible. We analysed time to treatment failure from start of adalimumab until the end of follow-up [July 2016]. Treatment failure was defined as drug discontinuation for secondary loss of response or serious adverse event or need for IBD-related surgery. Serum adalimumab concentrations and antibodies to adalimumab were measured using the Prometheus homogeneous mobility shift assay. Results A total of 382 patients with IBD [Crohn’s disease, n = 311, 81%] were included and received either at least one proactive TDM [n = 53] or standard of care [empirical dose escalation, n = 279; reactive TDM, n = 50]. Patients were followed for a median of 3.1 years [interquartile range, 1.4–4.8 years]. Multiple Cox regression analyses showed that at least one proactive TDM was independently associated with a reduced risk for treatment failure (hazard ratio [HR]: 0.4; 95% confidence interval [CI]: 0.2–0.9; p = 0.022). Conclusions This multicentre, retrospective cohort study reflecting real-life clinical practice provides the first evidence that proactive TDM of adalimumab may be associated with a lower risk of treatment failure compared with standard of care in patients with IBD.
Anti-tumor necrosis factor (TNF) therapy has revolutionized the medical treatment of the inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis. Twenty years ago, infliximab became the first anti-TNF agent approved for IBD. Data from randomized controlled trials, large observational cohort studies, postmarketing registries, and meta-analyses show that infliximab is a very effective treatment for moderate to severe IBD with a good safety profile. Infliximab has been also used to treat pouchitis following an ileal pouch–anal anastomosis (IPAA) after restorative proctocolectomy and to prevent postoperative recurrence following an ileocolonic resection for CD with good results. Nevertheless, up to 30% of patients show no clinical benefit following induction and up to 50% lose response over time. Both these unwanted outcomes can be largely explained by inadequate drug concentrations and frequently by the development of antibodies to infliximab. Loss of response can be managed efficiently and often prevented by applying therapeutic drug monitoring. Recently, the first biosimilars of infliximab have been approved and are utilized in clinical practice with comparable efficacy and safety with the originator. This review will mainly focus on the efficacy of infliximab in IBD.
Background: Patients with ulcerative colitis have an increased risk of colorectal cancer. We sought to assess the comparative efficacy of standard white-light endoscopy (SDWLE) or high-definition white-light endoscopy (HDWLE) versus dye-based chromoendoscopy through a meta-analysis and rate the quality of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. Methods: A systematic review of the literature in PubMed, EMBASE, and Web of Science was performed in April 2018. The primary outcome was the number of patients in whom dysplasia was identified using a per patient analysis in randomized controlled trials (RCT) and analyzed separately for non-RCTs. Analysis was performed using RevMan 5.3 reporting random-effects risk ratios. Results: Of the 27,904 studies identified, 10 studies were included 6 of which were RCTs (3 SDWLE and 3 HDWLE). Seventeen percent (84/494) of patients were noted to have dysplasia using chromoendoscopy compared with 11% (55/496) with white-light endoscopy (relative risk [RR] 1.50; 95% confidence interval [CI], 1.08-2.10). When analyzed separately, chromoendoscopy (n Z 249) was more effective at identifying dysplasia than SDWLE (n Z 248) (RR, 2.12; 95% CI, 1.15-3.91), but chromoendoscopy (n Z 245) was not more effective compared with HDWLE (n Z 248) (RR, 1.36; 95% CI, 0.84-2.18). The quality of evidence was moderate. In non-RCTs, dysplasia was identified in 16% (114/698) of patients with chromoendoscopy compared with 6% (62/1069) with white-light endoscopy (RR, 3.41; 95% CI, 2.13-5.47). Chromoendoscopy (n Z 58) was more effective than SDWLE (n Z 141) for identification of dysplasia (RR, 3.52; 95% CI, 1.38-8.99), and chromoendoscopy (n Z 113) was also more effective than HDWLE (n Z 257) (RR, 3.15; 95% CI, 1.62-6.13). The quality of the evidence was very low. Conclusion: Based on this meta-analysis, non-RCTs demonstrate a benefit of chromoendoscopy over SDWLE and HDWLE, whereas RCTs only show a small benefit of chromoendoscopy over SDWLE, but not over HDWLE.
Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. We sought to assess the comparative efficacy of virtual chromoendoscopy (VCE) vs high definition white light endoscopy (HDWLE) or dye-spraying chromoendoscopy (DCE) through a meta-analysis and rating the quality of evidence. Methods A systematic review of the literature was performed through February 15, 2019. Primary outcomes were number of patients in whom dysplasia was identified and number of dysplastic lesions identified in these patients. We included only randomized control trials (RCTs) and performed meta-analysis using RevMan5.3. Results Of the 3205 studies identified, 11 RCTs were included, with a total of 1328 patients. Per patient analysis, VCE was not statistically different compared with DCE (risk ratio [RR] 0.77; 95% CI, 0.55–1.08) or HDWLE (RR 0.72; 95% CI, 0.45–1.15). However, per dysplasia analysis, VCE was not statistically different compared with DCE (RR 0.72; 95% CI, 0.47–1.11) and inferior compared with HDWLE (RR 0.62; 95% CI, 0.44–0.88). The quality of evidence was moderate in the HDWLE and low to moderate in the DCE studies. Conclusion Based on this meta-analysis, VCE was as good as HDWLE and DCE in identifying dysplasia per patient analysis. However, per dysplasia analysis, VCE was inferior compared with HDWLE and no different from DCE. Further studies need to examine the efficacy of each individual VCE technique.
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