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-tumor 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 hospitalization, dose intensification or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included (67 infliximab, 61 adalimumab), mean age 37 (±SD 14) years, 71 (56%) females. Median disease duration was 8 (IQR 4-14) years. Clinical disease activity was present in 41/128 (32%) patients, 36/127 (28%) patients had a MMAS-8 <6 ("low adherence") and 25/99 (25%) patients had a MPR<80% (non-adherence). Risk factors for non-adherence included adalimumab use (OR 10.1, 95%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

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

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]. 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. 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. 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 outcome

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-tumor 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 hospitalization, dose intensification or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included (67 infliximab, 61 adalimumab), mean age 37 (±SD 14) years, 71 (56%) females. Median disease duration was 8 (IQR 4-14) years. Clinical disease activity was present in 41/128 (32%) patients, 36/127 (28%) patients had a MMAS-8 <6 ("low adherence") and 25/99 (25%) patients had a MPR<80% (non-adherence). Risk factors for non-adherence included adalimumab use (OR 10.1, 95%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

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

Multimodal treatment of perianal fistulas in Crohn's disease : Seton versus anti-TNF versus advancement plasty (PISA): Study protocol for a randomized controlled trial

Background: Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs. Methods/Design: This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs. Discussion: The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters. Trial registration: Nederlands Trial Register identifier: NTR4137(registered on 23 August 2013)