Low Trough Serum Infliximab and Antibodies to Infliximab in Smokers

Kong, Jee Yuen; Bundell, Christine; Pawlik, Janina; Hollingsworth, Peter; Forbes, Geoffrey M

doi:10.1002/ibd.22928

Cited by 7 publications

(6 citation statements)

References 7 publications

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“…Kong et al reported that smoking patients administered infliximab for CD had a median trough level of 0.34 mg/L versus 13.3 mg/L for non-smoking patients. [22] Furthermore, the level of antibodies against infliximab was significantly higher in smokers than in non-smokers, which is associated with a negative response to infliximab in CD. [22] Both smoking-induced systemic inflammation, including cytokine levels, and smoking-elevated basal metabolic rate [7] may interact to reduce the response of anti-rheumatoid drugs.…”

Section: Discussionmentioning

confidence: 95%

“…[22] Furthermore, the level of antibodies against infliximab was significantly higher in smokers than in non-smokers, which is associated with a negative response to infliximab in CD. [22] Both smoking-induced systemic inflammation, including cytokine levels, and smoking-elevated basal metabolic rate [7] may interact to reduce the response of anti-rheumatoid drugs. [40,41] The study findings were not statistically significant, although the smoking group was more likely to show lower response to TNF-α inhibitors than the non-smoking group.…”

Section: Discussionmentioning

confidence: 95%

“…[7,8,[10][11][12] Some studies defined the amount of smoking as more than 5 cigarettes per day within 6 months from initiation of drug administration, [16,19,20,28,29] more than 7 cigarettes per week, [18,26] more than 1 cigarette per day, [17] or the presence of smoking without considering cigarette numbers. [13][14][15][22][23][24][25]27,[31][32][33][34] These variable smoking definitions could contribute to the discrepancy in the study results. Third, we could not separately report individual TNF-α inhibitor drugs due to the small number of studies we analyzed.…”

Section: Discussionmentioning

confidence: 99%

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Impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis or Crohn's disease

Song

Sohn

Kim

et al. 2014

Transl Clin Pharmacol

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These authors contributed equally as co-first authorsCigarette smoking may be associated with the augmentation of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-α), which may affect the outcomes of pharmacological agents such as TNF-α inhibitors. The purpose of this study was to investigate the impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis (RA) or Crohn's disease (CD). We used systematic literature review methods. A total of 1,147 articles were selected after exclusion of duplicates through a database search. Among them, 28 articles were finally selected through a review of titles and abstracts and a subsequent review of full articles. The effectiveness of TNF-α inhibitors in patients with RA or CD among the selected articles was summarized by their smoking status. Meta-analysis was performed with random effect model. When current smokers were compared with non-smokers for response after adjustments through meta-analysis among patients with RA, current smokers had 59% less response than non-smokers with statistical significance (Pooled adjusted OR=0.41, 95% CI=0.17-0.95). In patients with CD, current smokers tended to have lower clinical response than non-smokers, but statistical significance was not shown. In subgroup analyses for luminar CD or fistulizing CD, current smokers tended to have a lower response in luminar CD (Pooled OR=0.62, 95% CI=0.34-1.14), but smoking status was not associated with drug response in fistulizing CD. This study raises awareness of the adverse effects of smoking in terms of clinical response in patients treated with TNF-α inhibitors.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis or Crohn's disease

Song

Sohn

Kim

et al. 2014

Transl Clin Pharmacol

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“…Patients and disease phenotypes: Factors predictive of longer time to failure include obesity, smoking, higher baseline serum albumin, male sex, and thiopurine co-therapy. Higher baseline fecal calprotectin is associated with shorter time to failure (21, 34, 35). Elevated body mass index (BMI) is associated with poorer response to IFX and correlates with higher drug levels, but not a higher response rate, suggesting that circulating drug levels do not correlate with tissue levels (36).…”

Section: Difficulties In Predicting Lor To Anti-tnfs In Ra and Ibd Prmentioning

confidence: 99%

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Khoury

Ilan

2019

Front. Immunol.

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Primary lack of response and secondary loss of response (LOR) are major obstacles to the use of anti–tumor necrosis factor (TNF)-based therapies in patients with rheumatoid arthritis or inflammatory bowel disease. Here, we review the mechanisms and methods for predicting LOR and the currently used methods for overcoming the ineffectiveness of anti-TNFs. The complex functions of TNF and anti-TNF antibodies, which can promote both pro- or anti-inflammatory actions, and the factors that affect the induction of immune tolerance to their effects are presented. The lack of rules and the continuous dynamics of the immune processes partly underlie the unpredictability of the response to anti-TNFs. Variability is inherent to biological systems, including immune processes, and intra/inter-patient variability has been described in the response to drugs. This variability is viewed as a compensatory adaptation mechanism of the immune system in response to drugs and may contribute to treatment LOR. Dose reductions and drug holidays have been tested in patients treated with anti-TNFs. Regular dose-based regimens may be incompatible with physiological variability, further contributing to treatment inefficacy. We present the concept of overcoming immune system adaptation to anti-TNFs by introducing patient-tailored patterns of variability to treatment regimens.

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“…Studies in healthy volunteers and patients with rheumatoid arthritis show that smokers have increased TNF-α release from peripheral blood monocytes and stimulated T lymphocytes. An increase of TNF-α could lead to consumption of IFX and to reduce serum drug levels [58].…”

Section: Metabolic and Environmental Factorsmentioning

confidence: 99%

Emerging Mechanisms of Action and Loss of Response to Infliximab in Ibd: A Broader Picture

Scaldaferri¹,

Pecere²

2015

Biochem Pharmacol (Los Angel)

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Biologic drugs, as Infliximab (IFX), are widely used in inflammatory bowel disease (IBD). IFX is a chimeric monoclonal immunoglobulin directed against TNF-α and acting in IBD through several mechanisms of action. We divide these mechanisms into central and peripheral. Central mechanisms are considered effective at systemic level, like the reduction of plasmatic pro-inflammatory cytokines (TNF-α, IFN-γ), the promotion of apoptosis of inflammatory cells, the induction of T regulatory cells (FOXP3CD4+) and the modulation of cellular inflammatory pathways. Peripheral mechanisms could be considered acting at mucosal levels like normalization of endothelial functions, blockade of angiogenesis, restoring balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matalloproteases (TIMPs). This classification could serve as solid guide to better categorize mechanisms of lack of response to IFX, which account for up to 30% of patients per year. Central mechanism of loss of response proposed are the formation of antiinfliximab antibodies (ATI), trough serum levels, metabolic factors and pharmacogenomics; peripheral mechanisms of loss of response could be the degradation of IFX by MMPs at mucosal level and the loss of IFX trough inflamed mucosa. In the present review, we analyze mechanisms of action and loss of response to IFX in course of IBD known until today.

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Low Trough Serum Infliximab and Antibodies to Infliximab in Smokers

Cited by 7 publications

References 7 publications

Impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis or Crohn's disease

Impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis or Crohn's disease

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Emerging Mechanisms of Action and Loss of Response to Infliximab in Ibd: A Broader Picture

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