Earlier discontinuation of TNF‐α inhibitor therapy in female patients with inflammatory bowel disease is related to a greater risk of side effects

Schultheiss, Johannes P D; Brand, Eelco C.; Lamers, Evert; Berg, Willemijn C.M. van den; Schaik, Fiona D.M. van; Oldenburg, Bas; Fidder, Herma H.

doi:10.1111/apt.15380

Cited by 28 publications

(32 citation statements)

References 64 publications

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“…A previous study demonstrated that non-adherence to ant-TNF agents is significantly associated with the incidence of LOR to an- ti-TNF agents [14]. A study conducted in the Netherlands revealed that drug persistence for anti-TNF in females was lower than that of males due to a higher rate of side effects in females [15]. The findings of these studies can serve as bases to support our hypothesis.…”

Section: Discussionsupporting

confidence: 74%

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

Hong

Park

Yoon

et al. 2021

Korean J Intern Med

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Background/Aims: Combination therapy with immunomodulators (IMMs) was proposed as a strategy to prevent the development of loss of response (LOR) to anti-tumor necrosis factor (TNF) for patients with inflammatory bowel disease (IBD). However, the effect is unclear in patients already exposed to IMMs. The aim of this study was to evaluate whether combination therapy with IMMs is superior to monotherapy for prevention of LOR to anti-TNF. Methods: This was a retrospective study of patients in Seoul National University Bundang Hospital with IBD between January 2009 and October 2018. LOR was defined as clinical deterioration after maintenance of anti-TNF for at least 6 months. We investigated the difference in incidence of LOR to anti-TNF between the monotherapy and combination groups. We additionally assessed factors affecting LOR development to anti-TNF. Results: A total of 116 patients with IBD were included in this study (monotherapy 61 patients; combination 55 patients). Overall, LOR to anti-TNF occurred in 31 patients during the follow-up period. The combination of an anti-TNF agent and IMM showed no significant difference in the incidence of LOR compared to anti-TNF agent monotherapy (hazard ratio [HR], 1.64; 95% confidence interval [CI], 0.786 to 3.148; p = 0.182). Female sex was significantly associated with the development of LOR to anti-TNF (HR, 3.032; 95% CI, 1.467 to 6.268; p = 0.003). Conclusions: Anti-TNF and IMM combination therapy did not prove efficacious in preventing the development of LOR in IBD patients. Female sex was associated with the development of LOR to anti-TNF; further studies are required to confirm these results.

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Section: Discussionsupporting

confidence: 74%

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

Hong

Park

Yoon

et al. 2021

Korean J Intern Med

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“… 40 A recent study published in 2019 reported that female sex was associated with a higher risk of discontinuation of anti-TNF therapy in IBD due to higher rates of drug intolerance. 41 In the same study, other factors such as greater age at start of anti-TNF therapy and dose escalation were found to be associated with discontinuation. 41 Similar findings were reported by another study where a greater age of patient was associated with higher risk of discontinuation and treatment failure.…”

Section: Discussionmentioning

confidence: 86%

“… 41 In the same study, other factors such as greater age at start of anti-TNF therapy and dose escalation were found to be associated with discontinuation. 41 Similar findings were reported by another study where a greater age of patient was associated with higher risk of discontinuation and treatment failure. 42 Our cohort identified some new risk factors which predict poor outcomes after discontinuation of biologics which could guide decision making.…”

Section: Discussionmentioning

confidence: 86%

Clinical outcomes, predictors of prognosis and health economics consequences in IBD patients after discontinuation of the first biological therapy

Shivaji

Bazarova²,

Critchlow

et al. 2020

Therap Adv Gastroenterol

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Background: In real-world clinical practice, biologics in inflammatory bowel diseases (IBD) may be discontinued for a variety of reasons, including discontinuation initiated by gastroenterologists. The aims of the study are to report outcomes after discontinuation and predictors of prognosis after a minimum follow-up of 24 months; outcomes of gastroenterologist-initiated discontinuation with resulting direct cost implications on the health system were also studied. Methods: IBD patients who discontinued their first-use biologics between January 2013 and December 2016 were identified at our tertiary centre. Reasons for discontinuation and pre-defined adverse outcomes (AO) were recorded. Data were analysed using univariable and multivariable logistic regressions within a machine learning technique to predict AO. Gastroenterologist-initiated discontinuations were analysed separately, and Kaplan–Meier survival analysis performed; direct costs of AO due to discontinuation were assessed. Results: A total of 147 patients discontinued biologics (M = 74; median age 39 years; Crohn’s Disease = 110) with median follow-up of 40 months (range 24–60 months). In the total cohort, there were fewer AO among gastroenterologist-initiated discontinuations compared with patient-initiated; 54% (of the total group) had AO within 6 months. Among 59 gastroenterologist-initiated discontinuations, 23 (40%) had IBD-related AO within 6 months and 53 (90%) patients had AO by end of follow-up. Some 44 (75%) patients needed to restart biologics during follow-up, and direct costs due to AO and restart of biologics were high. Conclusions: The proportion of patients who have AO following discontinuation of biologics is high; clinicians need to carefully consider predictors of poor prognosis and high relapse rates when discussing discontinuation. The direct costs of managing AO probably offset theoretical economic gains, especially in the era where cost of biologics is reducing. Biologics should probably be continued without interruptions in most patients who have achieved remission for the duration these remain effective and safe.

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“…Proinflammatory cytokines are known to be mediators during the onset of disease, and they play critical roles in immune status and inflammatory response. Tumor necrosis factor alpha (TNF-a) is one of the major proinflammatory factors relevant to the pathogenesis of IBD (Schultheiss et al, 2019). Popivanova et al (2008) reported that the combined treatment with Azoxymethane and DSS induced the intracolonic expression of TNF-a and blocking of TNF-a reversed carcinoma progression with less inflammatory infiltrate.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

Liu

et al. 2021

Front. Cell. Infect. Microbiol.

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This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer’s patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.

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Earlier discontinuation of TNF‐α inhibitor therapy in female patients with inflammatory bowel disease is related to a greater risk of side effects

Cited by 28 publications

References 64 publications

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

Clinical outcomes, predictors of prognosis and health economics consequences in IBD patients after discontinuation of the first biological therapy

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

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