Systematic review with meta‐analysis: association between acetaminophen and nonsteroidal anti‐inflammatory drugs (<scp>NSAID</scp>s) and risk of Crohn's disease and ulcerative colitis exacerbation

Moninuola, Oluwatoba; Milligan, William; Lochhead, Paul; Khalili, Hamed

doi:10.1111/apt.14606

Cited by 72 publications

(40 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Unlike COX-1, which is constitutively expressed in multiple tissues, including the gastrointestinal tract, the expression of COX-2 is typically induced by inflammation, such as TNF stimulation [ 14 , 15 ]. Additionally, COX-2 inhibitor treatment of UC patients has for a long time been linked with an increased risk of flaring disease [ 16 , 17 ], although a recently published meta-analysis has questioned this generalization in patients with IBD [ 18 ]. Further, the most abundant COX-derived metabolite [ 15 ], PGE 2 , has been shown to be required for intestinal wound repair by promoting the differentiation of wound-associated epithelial cells (WAE) [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

COX-2–PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis

Soendergaard

Bergenheim

et al. 2018

EBioMedicine

View full text Add to dashboard Cite

BackgroundInhibition of tumor necrosis factor-α (TNF) signaling is beneficial in the management of ulcerative colitis (UC), but up to one-third of patients do not have a clinical response of relevance to TNF inhibitors during induction therapy (i.e. primary non-responders [PNRs]). Through production of prostaglandins (PGs) and thromboxanes, cyclooxygenase-2 (COX-2) affects inflammation and epithelial regeneration and may in this way be implicated in treatment resistance to TNF inhibitors.MethodsIn this study, COX-2 expression was analyzed in human intestinal biopsies and patient-derived monocytes, and the downstream consequences of COX-2 activity was evaluated by assessing the influence of the down-stream effector, PGE2, on intestinal epithelial stem cell self-renewal and differentiation using primary human intestinal organoids (“mini-guts”).FindingsWe found that TNF stimulation induced COX-2 expression in monocytes isolated from responders (Rs), whereas COX-2 expression was constitutively high and non-inducible in monocytes from PNRs. Additionally, PGE2 in combination with proliferative signals transformed human intestinal epithelial cells to a proinflammatory state akin to flaring UC, whereas PGE2 in combination with differentiation signals supported robust mucin induction.InterpretationOur work indicates that COX-2-PGE2 signaling could be a novel target for the management of PNRs to TNF inhibitors. We additionally demonstrate that COX-2–PGE2 signaling has dual functions during tissue repair and normal lineage differentiation, explaining in part the lack of response to TNF inhibitors among PNRs.FundThis work was funded by grants from the Novo Nordisk Foundation, the Lundbeck Foundation, the Vanderbilt Digestive Disease Research Center, NIH Grants, Aase and Ejnar Danielsen's Foundation and the A.P. Møller Foundation.

show abstract

Section: Introductionmentioning

confidence: 99%

COX-2–PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis

Soendergaard

Bergenheim

et al. 2018

EBioMedicine

View full text Add to dashboard Cite

show abstract

“…Despite the substantial heterogeneity across the 18 studies, this systematic review concluded that both COX-2 and non-selective COX inhibitors appeared safe in IBD patients and should not be withheld. 36 In summary, current evidence consistently demonstrates the safety of COX-2 inhibitors in IBD, especially when used in the short term, up to 3 months. Despite early case reports suggesting potential for harm, meta-analyses have not demonstrated risk of disease flare even with nonselective NSAIDs, although results are drawn from heterogenous studies.…”

Section: Nsaids and Cox-2 Inhibitorsmentioning

confidence: 82%

Section: Nsaids and Cox-2 Inhibitorsmentioning

confidence: 99%

IBD considerations in spondyloarthritis

Jiang

Raine

2020

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

Spondyloarthritis (SpA) may be regarded a family of auto-inflammatory conditions with inflammation focused on the joints. These form part of a wider family of immune-mediated inflammatory diseases, which include inflammatory bowel diseases (IBD). These conditions share common elements of pathophysiology and it is perhaps unsurprising, therefore, that individuals with SpA frequently manifest gastrointestinal inflammation, to which the physician managing the patient with SpA must be alert. In this article, we review the shared epidemiology and pathophysiology of these conditions, before discussing approaches to diagnosis and management of inflammatory gastrointestinal pathology in patients seen in rheumatology clinics. In particular, we discuss the difference between non-specific gastrointestinal inflammation commonly described in this patient group and the more specific diagnosis of Crohn’s disease or ulcerative colitis. We describe the appropriate diagnostic workup for patients suspected of having IBD. In addition, we discuss how a diagnosis of IBD can inform treatment selection, highlighting important differences in treatment choice, drug dosing, monitoring and drug safety for this particular comorbid patient population.

show abstract

“…Patients with IBD-associated SpA are commonly treated with physical therapy and NSAIDs to relieve pain, swelling, and stiffness. Frequently used with success by rheumatologists, NSAIDs represent a very controversial option for IBD patients [20,21] as that they have been accused of inducing increased rate of flares, hospitalization, and complications [22,23], which are not found in a recent meta-analysis [24]. Therefore, NSAIDS should be used in the short term [25], or COX-2 inhibitors are an alternative option, as less negative data exist [26,27], or paracetamol in case of residual pain or only minimal inflammation.…”

Section: Treatment Of Arthropathies With Conventional Disease-modifyimentioning

confidence: 99%

Therapies in Inflammatory Bowel Disease Patients with Extraintestinal Manifestations

Juillerat

Manz²,

Sauter

et al. 2020

Digestion

View full text Add to dashboard Cite

Extraintestinal manifestations (EIM) have become an important source of morbidity and disability as well as an identified risk factor for an unfavorably course of disease in inflammatory bowel diseases (IBD). Therefore, efforts have been put into a more global and interdisciplinary management of IBD patients in collaboration with rheumatologists, dermatologists, and ophthalmologists. A real therapeutic success has also been obtained with a more "systemic" IBD treatment associated with the development of monoclonal antibodies against TNF alpha and biological agents derived from the treatment of rheumatological disease (also called biological Disease-Modifying Antirheumatic Drugs). The prevalence of these EIM remains too low to undergo randomized controlled trials with this specific focus and therefore the evidence relies on case series and experts' opinions, which lowers the level of evidence. After a careful review of the most recent literature, this paper aims to update the reader on the latest therapeutic management of IBD patients with EIM.

show abstract

Systematic review with meta‐analysis: association between acetaminophen and nonsteroidal anti‐inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation

Abstract: Contrary to generally accepted belief, we did not find a consistent association between NSAIDs use and risk of CD and UC exacerbation. There was also no consistent evidence for association with acetaminophen although further studies are needed.

Cited by 72 publications

References 57 publications

COX-2–PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis

COX-2–PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis

IBD considerations in spondyloarthritis

Therapies in Inflammatory Bowel Disease Patients with Extraintestinal Manifestations

Contact Info

Product

Resources

About