Impact of comorbidities on anti-TNFα response and relapse in patients with inflammatory bowel disease: the VERNE study

Marín-Jiménez, Ignacio; Bastida, Guillermo; Forés, Ana; García‐Planella, Esther; Argüelles‐Arias, Federico; Sarasa, P; Tagarro, Ignacio; Fernández-Nistal, Alonso; Montoto, Carmen; Aguas, Mariam; Santos-Fernández, Javier; Bosca-Watts, Marta Maia; Ferreiro, Rocío; Merino, Olga; Aldeguer, Xavier; Cortés, Xavier; Sicilia, Beatriz; Mesonero, Francisco; Acosta, Manuel Barreiro‐de

doi:10.1136/bmjgast-2019-000351

Cited by 8 publications

(6 citation statements)

References 43 publications

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“…A recently published study showed that the presence of the comorbidities chronic obstructive pulmonary disease as well as extra-intestinal hepato-pancreato-biliary conditions were associated with primary non-response and myocardial infarction and skin disease were significantly associated with loss of response to anti-TNF treatment ( 52 ). Further studies will have to investigate these findings.…”

Section: Patient and Disease Related Predictors To Anti-tnf Therapymentioning

confidence: 99%

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

2020

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The advent of anti-TNF agents as the first approved targeted therapy in the treatment of inflammatory bowel disease (IBD) patients has made a major impact on our existing therapeutic algorithms. They have not only been approved for induction and maintenance treatment in IBD patients, but have also enabled us to define and achieve novel therapeutic outcomes, such as combination of clinical symptom control and endoscopic remission, as well as mucosal healing. Nevertheless, approximately one third of treated patients do not respond to initiated anti-TNF therapy and these treatments are associated with sometimes severe systemic side-effects. There is therefore the currently unmet clinical need do establish predictive markers of response to identify the subgroup of IBD patients, that have a heightened probability of response. There have so far been approaches from different fields of IBD research, to descry markers that would empower us to apply TNF-inhibitors in a more rational manner. These markers encompass findings from disease-related and clinical factors, pharmacokinetics, biochemical markers, blood and stool derived parameters, pharmacogenomics, microbial species, metabolic compounds, and mucosal factors. Furthermore, changes in the intestinal immune cell composition in response to therapeutic pressure of anti-TNF treatment have recently been implicated in the process of molecular resistance to these drugs. Insights into factors that determine resistance to anti-TNF therapy give reasonable hope, that a more targeted approach can then be utilized in these non-responders. Here, IL-23 could be identified as one of the key factors determining resistance to TNF-inhibitors. Growing insights into the molecular mechanism of action of TNF-inhibitors might also enable us to derive critical molecular markers that not only mediate the clinical effects of anti-TNF therapy, but which level of expression might also correlate with its therapeutic efficacy. In this narrative review, we present an overview of currently identified possible predictive markers for successful anti-TNF therapy and discuss identified molecular pathways that drive resistance to these substances. We will also point out the necessity and difficulty of developing and validating a diagnostic marker concerning clinically relevant outcome parameters, before they can finally enter daily clinical practice and enable a more personalized therapeutic approach.

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Section: Patient and Disease Related Predictors To Anti-tnf Therapymentioning

confidence: 99%

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

2020

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“…In any case, in our study, ADA results in the UC cohort should be interpreted cautiously due to the limited number of patients included in this subgroup [20] . These results are somewhat in accordance with those of other published retrospective analyses where UC patients treated with ADA showed higher, albeit not statistically significant, treatment discontinuation rates than those treated with IFX [18 , 43-46] .…”

Section: Article In Pressmentioning

confidence: 91%

“…The study was reviewed and approved by the corresponding ethics committees. The results obtained in the VERNE study on the impact of both comorbidities and extraintestinal manifestations (EIMs) on the response to anti-TNF α therapy have been published elsewhere [20] .…”

Section: Study Populationmentioning

confidence: 99%

Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study

Bastida¹,

Marín-Jiménez²,

Forés³

et al. 2022

Digestive and Liver Disease

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Background: Anti-TNF α represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. Aims:To assess the treatment patterns with the first anti-TNF α in IBD.Methods: Retrospective, observational study.Results: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC.Conclusions: Around one-third of IBD biologic-naive patients treated with an anti-TNF α required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNF α due to inappropriate disease control.

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“…Our study shows that comorbidities were another important factor affecting the expenses of CD hospitalization. The presence of comorbidities in IBD patients had been proven to adversely affect their health-related quality of life, prolong their hospital stay and increase the risk of postoperative complications (26). Possibly due to common pathogenic pathways with other immune-mediated inflammatory diseases, CD has been associated with multiple chronic comorbidities such as bone diseases, cardiovascular diseases, iron-deficiency anemia, pain, psychological disorders and respiratory illness.…”

Section: P-value Adj P-valuementioning

confidence: 99%

Assessment of influencing factors of hospitalization expenses for Crohn's disease patients: Based on LASSO and linear mixed model

Lai

et al. 2022

Front. Public Health

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AimsCrohn's disease (CD) is a global disease that is dramatically increasing. This study aimed to identify the primary drivers of hospitalization expenses for CD patients to provide guidance on the allocation and control of health care costs.MethodsThis study retrospectively collected the homepage data of the electronic medical records of CD patients in two tertiary hospitals in Zhejiang Province, China, from January 2016 to December 2021. The influencing factors of hospitalization expenses for CD were analyzed. A linear mixed model with least absolute shrinkage (LASSO-LMM) was used to develop a predictive model for hospitalization expenses for CD patients.ResultsA total of 4,437 CD patients were analyzed in this study. CD patients' age, length of hospital stay, admission route, comorbidities, and main treatment were found to be statistically significant variables for CD patients' hospitalization expenses. The AIC and BIC of LASSO-LMM model were 319.033 and 306.241, respectively. Patients who were older, had a longer hospital stay, and had comorbidities had higher hospitalization expenses. The hospitalization expenses of outpatients were lower than those of emergency patients. The weight of surgical treatment was the highest among three treatments (0.602).ConclusionsIdentifying and examining factors that influence hospitalization expenses for CD patients can help to control healthcare expenditures. Treatment mode was the most important impact on CD hospitalization expenses. Medical security departments can consider implement personalized and precise hospitalization expense compensation scheme base on LASSO-LMM prediction model in the future.

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Impact of comorbidities on anti-TNFα response and relapse in patients with inflammatory bowel disease: the VERNE study

Cited by 8 publications

References 43 publications

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study

Assessment of influencing factors of hospitalization expenses for Crohn's disease patients: Based on LASSO and linear mixed model

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