Comparative analysis of the influence of clinical factors including BMI on adalimumab and infliximab trough levels

Bond, Ashley; Asher, Rebecca; Jackson, Richard; Sager, Khalid; Martin, Kate; Kneebone, Andrew; Philips, Suzannah; Taylor, William F.; Subramanian, Sreedhar

doi:10.1097/meg.0000000000000544

Cited by 28 publications

(22 citation statements)

References 34 publications

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“…However, these findings have not been consistent. In a prospective, single-centre experience, no statistically significant association was observed between BMI and infliximab or adalimumab trough levels 97 .…”

Section: Obesity and Ibd-related Therapymentioning

confidence: 83%

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Singh

Dulai

Zarrinpar

et al. 2016

Nat Rev Gastroenterol Hepatol

319

285

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Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

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Section: Obesity and Ibd-related Therapymentioning

confidence: 83%

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Singh

Dulai

Zarrinpar

et al. 2016

Nat Rev Gastroenterol Hepatol

319

285

View full text Add to dashboard Cite

show abstract

“…In the CLASSIC‐II post hoc analysis, patients with a BMI >29 kg/m 2 were less often in clinical remission compared to patients with a lower BMI . Additionally, a recent report by Bond et al demonstrated that BMI did not differentially influence trough levels of adalimumab and IFX, but the investigators showed a trend towards a lower trough level in adalimumab‐treated patients with a BMI >30 kg/m 2 . Thus, BMI seems to influence the response to adalimumab.…”

Section: Discussionmentioning

confidence: 96%

Significance of measurement of serum trough level and anti‐drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial

Nakase¹,

Motoya²,

Matsumoto³

et al. 2017

Aliment Pharmacol Ther

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SummaryBackgroundSignificance of monitoring adalimumab trough levels and anti‐adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear.AimTo evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial.MethodsWe performed this study using adalimumab trough levels, AAA at week 26 and 6‐thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity.ResultsThere was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P <.001). Adalimumab trough level of 5.0 μg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 (P = .021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut‐off 6TGN level of >222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity.ConclusionAdalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146)

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“…A reduction in clinical outcome and lower trough levels in response to the TNFα antibody medications for Infliximab [133] and Adalimumab [134,135] have been reported. However, not all studies concurred with this observation [136]. A recent meta-analysis of therapeutic outcome with different biological agents in various inflammatory disorders reported that the risk of therapeutic failure was 60% higher in obese patients.…”

Section: Impact Of Obesity On Clinical Outcome Of Ibdmentioning

confidence: 99%

Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms

Szilagyi

2019

Clin J Gastroenterol

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The inflammatory bowel diseases, Crohn's and ulcerative colitis have increased in incidence and prevalence from the mideighteen to the late nineteen centuries. From then to the current twenty-first century there has been a more rapid expansion of these disease to areas previously experiencing low rates. This latter expansion coincides with the current obesity pandemic which also began toward the end of the last century. Although the two diseases have radically different frequencies, there are interesting links between them. Four areas link the diseases. On an epidemiological level, IBD tends to follow a northsouth gradient raising the importance of vitamin D in protection. Obesity has very weak relationship with latitude, but both diseases follow adult lactase distributions colliding in this plane. Is it possible that obesity (a low vitamin D condition with questionable response to supplements) reduces effects in IBD? On a pathogenic level, pro-inflammatory processes mark both IBD and obesity. The similarity raises the question of whether obesity could facilitate the development of IBD. Features of the metabolic syndrome occur in both, with or without obesity in IBD. The fourth interaction between the two diseases is the apparent effect of obesity on the course of IBD. There are suggestions that obesity may reduce the efficacy of biologic agents. Yet there is some suggestion also that obesity may reduce the need for hospitalization and surgery. The apparent co-expansion of both obesity and IBD suggests similar environmental changes may be involved in the promotion of both.

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Comparative analysis of the influence of clinical factors including BMI on adalimumab and infliximab trough levels

Cited by 28 publications

References 34 publications

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Significance of measurement of serum trough level and anti‐drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial

Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms

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