Integrating new and emerging therapies into inflammatory bowel disease clinical practice

Sekhri, Shaina; Yarur, Andrés

doi:10.1097/mog.0000000000000851

Cited by 5 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike monoclonal antibody drugs which have few, mainly pharmacodynamic, interactions with other medications, the advent of small molecule drugs in clinical practice and in advanced stages of development, makes it pertinent for IBD experts to consider and monitor potential drug-interactions that may occur with these new classes of drugs. 5 Using regulatory administration guidelines from both American Food and Drug Administration and the European Medicines Agency, as well as published research and pharmaceutical companies' publications, we covered the main metabolizing enzymes and transporters involved in the pharmacokinetics of the first five small molecules used for the treatment of IBD: Tofacitinib, Upadacitinib, Filgotinib, Ozanimod, and Etrasimo. In addition, the review addresses the Food and Drug Administration's approach to determining drug-interaction hazard thresholds using their published "development resources" data pages.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease

Harnik,

Ungar,

Loebstein

et al. 2024

UEG Journal

View full text Add to dashboard Cite

Small molecule drugs are becoming increasingly used in the treatment of inflammatory bowel diseases (IBD). However, unlike monoclonal antibody drugs, which have few interactions with other medications, the pharmacokinetics of small molecule drugs are complex and may be influenced by a myriad of drug‐drug interactions (DDI) as well as by patient characteristics and food intake. This review aims to provide a concise practical guide to small molecule drug interactions for the use of IBD physicians. It starts with a brief overview of the main metabolizing enzymes and transporters involved in drug interactions and the Food and Drug Administration's (FDA) approach to determining drug‐interaction hazard thresholds. It is then followed by a more detailed review of the pharmacokinetics of four novel small molecules approved in IBD: Tofacitinib, Upadacitinib, Filgotinib, and Ozanimod, including their known interactions and specific warnings. This review will also inform readers on challenges in determining the actual magnitude of interactions and their clinical relevance, including the arbitrary nature of some hazard thresholds, the inference of the impact on metabolizing enzymes and transporters from single‐drug assays which may not reflect poly‐pharmaceutical regimens, and other challenges in this field which the IBD physician needs to be cognizant of. In practice, before administering a small molecule drug, it is advisable to evaluate any potential interactions with other medications the patient is receiving. An increased awareness by health care professionals and patients, may reduce the possible risks associated with DDI of small molecule IBD drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease

Harnik,

Ungar,

Loebstein

et al. 2024

UEG Journal

View full text Add to dashboard Cite

show abstract

“…The common purpose of this wide range of pharmacological therapy for IBDs is to suppress abnormal inflammatory response, fixing the immune dysregulation [ 5 ]. Indeed, because biological therapies have been introduced, the goal of IBD treatment has changed from simple clinical remission—or avoidance of surgery—to deep remission [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Quality of Life (QoL) in Patients with Chronic Inflammatory Bowel Diseases: How Much Better with Biological Drugs?

Bellone,

Morace,

Impalà

et al. 2023

JPM

View full text Add to dashboard Cite

Background: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients’ HRQoL remains to be explored. Aim: To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). Material and Methods: A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey–Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment–General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. Results: Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. Conclusions: Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life’s spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated.

show abstract

“…It is generally accepted that IBD are caused by an abnormal immune response to the gut microbiota in genetically susceptible subjects; however, although molecular mechanisms leading to IBD have been deeply investigated, a comprehensive understanding of the disease etiopathogenesis remains uncertain, hampering the development of effective therapeutic strategies. Indeed, the current therapies for IBD include a wide repertoire of drugs, including amino salicylates, glucocorticoids, immunomodulators and targeted biologicals [ 2 , 3 , 4 ], Nonetheless, the identification of new molecular targets for the development of additional treatment options is of high clinical priority.…”

Section: Introductionmentioning

confidence: 99%

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids

Vitali

Mancuso

Palone

et al. 2023

IJMS

View full text Add to dashboard Cite

Extracellular High-mobility group box 1 (HMGB1) contributes to the pathogenesis of inflammatory disorders, including inflammatory bowel diseases (IBD). Poly (ADP-ribose) polymerase 1 (PARP1) has been recently reported to promote HMGB1 acetylation and its secretion outside cells. In this study, the relationship between HMGB1 and PARP1 in controlling intestinal inflammation was explored. C57BL6/J wild type (WT) and PARP1−/− mice were treated with DSS to induce acute colitis, or with the DSS and PARP1 inhibitor, PJ34. Human intestinal organoids, which are originated from ulcerative colitis (UC) patients, were exposed to pro-inflammatory cytokines (INFγ + TNFα) to induce intestinal inflammation, or coexposed to cytokines and PJ34. Results show that PARP1−/− mice develop less severe colitis than WT mice, evidenced by a significant decrease in fecal and serum HMGB1, and, similarly, treating WT mice with PJ34 reduces the secreted HMGB1. The exposure of intestinal organoids to pro-inflammatory cytokines results in PARP1 activation and HMGB1 secretion; nevertheless, the co-exposure to PJ34, significantly reduces the release of HMGB1, improving inflammation and oxidative stress. Finally, HMGB1 release during inflammation is associated with its PARP1-induced PARylation in RAW264.7 cells. These findings offer novel evidence that PARP1 favors HMGB1 secretion in intestinal inflammation and suggest that impairing PARP1 might be a novel approach to manage IBD.

show abstract

Integrating new and emerging therapies into inflammatory bowel disease clinical practice

Cited by 5 publications

References 54 publications

A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease

A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease

Quality of Life (QoL) in Patients with Chronic Inflammatory Bowel Diseases: How Much Better with Biological Drugs?

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids

Contact Info

Product

Resources

About