The most commonly used TNF- inhibitors in people with inflammatory bowel disease are infliximab, adalimumab, and certolizumab pegol. inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period. Results Within the 90 days risk period, 51 cases of infection were observed in users of TNF- inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12). Conclusions This nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF- inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential infectious complications among people with inflammatory bowel disease using these drugs, especially early in the course of treatment. Introduction Tumour necrosis factor- (TNF-) inhibitors are highly effective in the treatment of several immune mediated diseases, including inflammatory bowel diseases. The most commonly used TNF- inhibitors in people with inflammatory bowel disease are infliximab, adalimumab, and certolizumab pegol. All three drugs are approved for the treatment of Crohns disease, whereas only infliximab and adalimumab are approved for the treatment of ulcerative colitis.1 2 3 4 5 6 Since the pro-inflammatory cytokine TNF- plays an important role in host defence, treatment with TNF- inhibitors has been subject to extensive post-marketing safety assessment, including the risk of infections. Studies assessing the risk of serious infections in people treated with TNF- inhibitors for rheumatoid arthritis have gradually revealed a largely coherent pattern of a moderately increased risk of serious infections in the initial phase of treatment and a subsequent decline in risk.7 8 9 10 Data are, however, less clear when it comes to the risk of serious infections in people treated with TNF- inhibitors for inflammatory bowel diseases. A meta-analysis based on 22 randomised controlled trials11 and a pooled analysis of 10 randomised controlled trials12 did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF- inhibitors compared with placebo. However, randomised controlled trials often represent selected patient populations, which is why post-marketing observational studies are essential to evaluate safety in a real world setting. A register based cohort study of people with inflammatory bowel disease Demethoxydeacetoxypseudolaric acid B analog did not find an increased risk of serious infections associated with TNF- inhibitor treatment compared with propensity score matched patients treated with thiopurines.13 However, another register based study reported an increased risk of serious infections associated with infliximab use in people with inflammatory bowel disease,14 as did a study based on data from the Food and Drug Administration Adverse Event Reporting System.15 Thus the risk of infections associated with use of TNF- inhibitors in people with inflammatory bowel disease is unclear. We conducted a nationwide populace based cohort study using linked registry data to investigate the risk of serious infections in Danish people with inflammatory bowel disease treated with TNF- inhibitors. Methods Using Demethoxydeacetoxypseudolaric acid B analog the Danish civil registration system,16 which contains information around the sex, date of birth, and vital status of all Danish citizens, we identified a source populace, including all individuals aged 15-75 years living in Denmark between 2002 and 2012. By use of the unique personal identification number assigned to all Danish citizens at birth, we could link the source populace to other national registries. From the national patient registry,17 a registry containing information on all hospital admissions in Denmark since 1977, and since 1995 extended to include all outpatient visits and emergency room contacts, we identified people with inflammatory bowel disease from ICD-8 and ICD-10 codes (international classification of diseases, eighth and 10th revisions, respectively): ICD-8 codes 56300-02 and 56308-09 and ICD-10 code K50 for Crohns disease; ICD-8 codes 56319 and 56309 and ICD-10 code K51 for.In preliminary analyses we attempted propensity score adjustment on the full background cohort. of TNF- inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period. Results Within the 90 days risk period, 51 cases of infection were observed in users of TNF- inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12). Conclusions This nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF- inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential infectious complications among people with inflammatory bowel disease using these drugs, especially early in the course of treatment. Introduction Tumour necrosis factor- (TNF-) inhibitors are highly effective in the treatment of several immune mediated diseases, including inflammatory bowel diseases. The most commonly used TNF- inhibitors in people with inflammatory bowel disease are infliximab, adalimumab, and certolizumab pegol. All three drugs are approved for the treatment of Crohns disease, whereas only infliximab and adalimumab are approved for the treatment of ulcerative colitis.1 2 3 4 5 6 Since the pro-inflammatory cytokine TNF- plays an important role in host defence, treatment with TNF- inhibitors has been subject to extensive post-marketing safety assessment, including the risk Demethoxydeacetoxypseudolaric acid B analog of infections. Studies assessing the risk of serious infections in people treated with TNF- inhibitors for rheumatoid arthritis have gradually revealed a largely coherent pattern of a moderately increased risk of serious infections in the initial phase of treatment and a subsequent decline in risk.7 8 9 10 Data are, however, less clear Rabbit Polyclonal to FGFR1/2 when it comes to the risk of serious infections in people treated with TNF- inhibitors for inflammatory bowel diseases. A meta-analysis based on 22 randomised controlled trials11 and a pooled analysis of 10 randomised controlled trials12 did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF- inhibitors compared with placebo. However, randomised controlled trials often represent selected patient populations, which is why post-marketing observational Demethoxydeacetoxypseudolaric acid B analog studies are essential to evaluate safety in a real world setting. A register based cohort study of people with inflammatory bowel disease did not find an increased risk of serious infections associated with TNF- inhibitor treatment compared with propensity score matched patients treated with thiopurines.13 However, another register based study reported an increased risk of serious infections associated with infliximab use in people with inflammatory bowel disease,14 as did a study based on data from the Food and Drug Administration Adverse Event Reporting System.15 Thus the risk of infections associated with use of TNF- inhibitors in people with inflammatory bowel disease is unclear. We conducted a nationwide population based cohort study using linked registry data to investigate the risk of serious infections in Danish people with inflammatory bowel disease treated with TNF- inhibitors. Methods Using the Danish civil registration system,16 which contains information on the sex, date of birth, and vital status of all Danish citizens, we identified a source population, including all individuals aged 15-75 years living in Denmark between 2002 and 2012. By use of the unique personal identification number assigned to all.This left a background cohort of 52?392 people with inflammatory bowel disease, among whom 4300 received TNF- inhibitors. the analyses. Main outcome measures The main outcome was any serious infection, defined as a diagnosis of infection associated with hospital admission. Cox regression was used to estimate hazard ratios for two risk periods (90 and 365 days after the start of TNF- inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period. Results Within the 90 days risk period, 51 cases of infection were observed in users of TNF- inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12). Conclusions This nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF- inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential infectious complications among people with inflammatory bowel disease using these drugs, especially early in the course of treatment. Introduction Tumour necrosis factor- (TNF-) inhibitors are highly effective in the treatment of several immune mediated diseases, including inflammatory bowel diseases. The most commonly used TNF- inhibitors in people with inflammatory bowel disease are infliximab, adalimumab, and certolizumab pegol. All three drugs are approved for the treatment of Crohns disease, whereas only infliximab and adalimumab are approved for the treatment of ulcerative colitis.1 2 3 4 5 6 Since the pro-inflammatory cytokine TNF- plays an important role in host defence, treatment with TNF- inhibitors has been subject to extensive post-marketing safety assessment, including the risk of infections. Studies assessing the risk of serious infections in people treated with TNF- inhibitors for rheumatoid arthritis have gradually revealed a largely coherent pattern of a moderately increased risk of serious infections in the initial phase of treatment and a subsequent decline in risk.7 8 9 10 Data are, however, less clear when it comes to the risk of serious infections in people treated with TNF- inhibitors for inflammatory bowel diseases. A meta-analysis based on 22 randomised controlled trials11 and a pooled analysis of 10 randomised controlled trials12 did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF- inhibitors compared with placebo. However, randomised controlled trials often represent selected patient populations, which is why post-marketing observational studies are essential to evaluate security in a real world establishing. A register centered cohort study of people with inflammatory bowel disease did not find an increased risk of severe infections associated with TNF- inhibitor treatment compared with propensity score matched individuals treated with thiopurines.13 However, another register based study reported an increased risk of serious infections associated with infliximab use in people with inflammatory bowel disease,14 as did a study based on data from the Food and Drug Administration Adverse Event Reporting System.15 Thus the risk of infections associated with use of TNF- inhibitors in people with inflammatory bowel disease is unclear. We carried out a nationwide human population based cohort study using linked registry data to investigate the risk of severe infections in Danish people with inflammatory bowel disease treated with TNF- inhibitors. Methods Using the Danish civil sign up system,16 which contains info within the sex, day of birth, and vital status of all Danish residents, we recognized a source human population, including all individuals aged 15-75 years living in Denmark between 2002 and 2012. By use of the unique personal identification.
The most commonly used TNF- inhibitors in people with inflammatory bowel disease are infliximab, adalimumab, and certolizumab pegol