Validation and update of a prediction model for risk of relapse after cessation of anti-TNF treatment in Crohn's disease.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy. METHODS: We performed a retrospective cohort study in 17 Dutch hospitals. Crohn's disease patients in clinical, biochemical or endoscopic remission were included after anti-TNF cessation. Primary outcome was a relapse necessitating treatment. Discrimination and calibration of the previously developed model were assessed. After external validation, the model was updated. The performance of the updated prediction model was assessed in internal-external validation and by using decision curve analysis. RESULTS: 486 patients were included with a median follow-up of 1.7 years. Relapse rates were 35 and 54% after 1 and 2 years. At external validation, the discriminative ability of the prediction model was equal to that found at the development of the model [c-statistic 0.58 (95% confidence interval (CI) 0.54-0.62)], though the model was not well-calibrated on our cohort [calibration slope: 0.52 (0.28-0.76)]. After an update, a c-statistic of 0.60 (0.58-0.63) and calibration slope of 0.89 (0.69-1.09) were reported in internal-external validation. CONCLUSION: Our previously developed and updated prediction model for the risk of relapse after cessation of anti-TNF in Crohn's disease shows reasonable performance. The use of the model may support clinical decision-making to optimize patient selection in whom anti-TNF can be withdrawn. Clinical validation is ongoing in a prospective randomized trial.

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events.

PURPOSE: To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. METHODS: Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. RESULTS: In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. CONCLUSION: Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

Non-adherence to Anti-TNF Therapy is Associated with Illness Perceptions and Clinical Outcomes in Outpatients with Inflammatory Bowel Disease: Results from a Prospective Multicentre Study.

BACKGROUND AND AIMS: Non-adherence to anti-tumour necrosis factor [TNF] agents in patients with inflammatory bowel disease [IBD] is a serious problem. In this study, we assessed risk factors for non-adherence and examined the association between adherence to anti-TNF agents and loss of response [LOR]. METHODS: In this multicentre, 12-month observational study, outpatients with IBD were included. Demographic and clinical characteristics were recorded. Adherence was measured with the Modified Morisky Adherence Scale-8 [MMAS-8] and 12-month pharmacy refills [medication possession ratio, MPR]. Risk factors included demographic and clinical characteristics, medication beliefs, and illness perceptions. Cox regression analysis was performed to determine the association between MPR and LOR to anti-TNF, IBD-related surgery or hospitalisation, dose intensification, or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included [67 infliximab, 61 adalimumab], mean age 37 ( ± standard deviation [SD] 14) years, 71 [56%] female. Median disease duration was 8 (interquartile range [IQR] 4-14) years. Clinical disease activity was present in 41/128 [32%] patients, 36/127 [28%] patients had an MMAS-8 < 6 ['low adherence'], and 25/99 [25%] patients had an MPR < 80% [non-adherence]. Risk factors for non-adherence included adalimumab use (odds ratio [OR] 10.1, 95% confidence interval [CI] 2.62-40.00), stronger emotional response [OR 1.16, 95% CI 1.02-1.31], and shorter timeline perception, i.e. short perceived illness duration [OR 0.60, 95% CI 0.38-0.96]. Adherence is linearly and negatively [OR 0.14, 95% CI 0.03-0.63] associated with LOR. CONCLUSION: Non-adherence to anti-TNF agents is strongly associated with LOR to anti-TNF agents, adalimumab use, and illness perceptions. The latter may provide an important target for interventions aimed at improving adherence and health outcomes.

Severe acute pancreatitis after EUS-FNA of a pancreatic cyst: a rare, but serious complication.

As a consequence of improved quality of abdominal imaging techniques in the last decades, discovery of pancreatic cystic lesions has become more common. The clinical significance of these lesions is often unclear and poses a diagnostic dilemma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a subject of debate regarding its role in the diagnostic evaluation of pancreatic masses and cysts. Although risks associated with the procedure are low, consequences can be serious and even life-threatening. We report a case of a previously healthy 59-year-old woman who suffered severe acute pancreatitis after EUS-FNA of a pancreatic cyst, requiring admission to the intensive care unit (ICU). Development of infected pancreatic necrosis and, successively, bowel ischaemia, led to multiple organ failure. Despite maximal antibiotic and surgical treatment the patient succumbed to refractory septic shock. The fatal outcome of this case illustrates the importance of balanced decision-making in the diagnostic approach of pancreatic cystic lesions.

Adalimumab and infliximab are equally effective for Crohn's disease in patients not previously treated with anti-tumor necrosis factor-α agents.

BACKGROUND & AIMS: Infliximab (IFX) and adalimumab (ADA) are thought to have equal efficacy for the treatment of Crohn's disease (CD), although no direct comparison has been performed. We compared the effectiveness and safety of IFX and ADA in carefully matched cohorts. METHODS: We performed a retrospective cohort study of 200 patients with CD (100 treated with IFX and 100 treated with ADA, starting in 2006 or later) who had not received anti-tumor necrosis factor α agents previously; the patients were identified from databases of 6 hospitals in The Netherlands. The groups were matched carefully for indication, duration of disease, age, and Montreal classification. The primary end point was the steroid-free clinical response, defined by a combination of multiple clinical parameters, after 1 year. RESULTS: Of the total patient population, 63.5% and 45% had a clinical response after 1 and 2 years, respectively. There were no significant differences between treatment groups: at 1 and 2 years, 62% and 41% of those receiving ADA vs 65% and 49% of those receiving IFX had responses, respectively. Kaplan-Meier curves showed identical decreases in response rates over time. Combining IFX or ADA with immunomodulator therapy was associated with a higher clinical response than monotherapy, although this was only significant among patients who received IFX (P = .03). There were no differences in numbers of side effects or opportunistic infections. CONCLUSIONS: The effectiveness of ADA or IFX treatment in anti-tumor necrosis factor α-naive patients with CD is comparable after 1 and 2 years of follow-up evaluation. The efficacies of IFX and ADA each seem to increase when given with immunomodulator therapy, although only significantly for IFX.

Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia.

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolic events. Aim of this study was to examine the relationship of hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of this factor in addition to other known prothrombotic abnormalities. IBD patients with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after methionine loading. Plasma levels of protein C, protein S, antithrombin III, and fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies were determined and genetic testing for factor V Leiden and the prothrombin gene mutation was performed. Results showed that fasting homocysteine levels in IBD patients with a history of arterial or venous thrombosis tended to be higher than in IBD controls, although not significantly. The increase in homocysteine levels after methionine loading was significantly higher in IBD patients in the arterial thrombosis group than in IBD controls (40.9 +/- 17.7 vs. 27.2 +/- 9.9 microM; P < 0.05). Among the other prothrombotic factors, only factor V Leiden was significantly associated with a history of venous thrombosis (20 vs. 0%). At least one risk factor was found in 64% of the IBD patients with previous thromboembolic complications. We conclude that there is an association between hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We confirm the high prevalence of factor V Leiden in IBD patients with a history of venous thrombosis. In the majority of IBD patients with previous thromboembolic complications, at least one prothrombotic risk factor is detected.