scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

Therapeutic drug monitoring of adalimumab in inflammatory bowel disease in children

2021 ◽  
Vol 19 (3) ◽  
pp. 14-25
Author(s):  
A.S. Illarionov ◽  
◽  
T.V. Radygina ◽  
A.S. Potapov ◽  
A.P. Fisenko ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Tumor Necrosis ◽  
Therapeutic Drug ◽  
Endoscopic Remission ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Objective. To evaluate the significance of therapeutic drug monitoring of adalimumab (ADA) concentration levels and antibodies to it in inflammatory bowel disease (IBD) in children. Patients and methods. In this study, 103 children with IBD (24 patients with ulcerative colitis (UC) and 79 with Crohn’s disease (CD)) aged 3–18 years were examined during maintenance therapy with ADA (100 mg/mL in 0.4 mL). Body weight, duration of disease and therapy, use of azathioprine (AZA), achievement of clinical and endoscopic remission, albumin levels, residual levels of ADA and antibodies to the drug, circulating cytokine levels in serum were assessed. Results. A significant decrease in ADA levels in children in the absence of clinical remission in CD (5.21 [3.32; 7.43] μg/mL in remission) and in UC (2.42 [0.42; 4.51] μg/mL, p = 0.001) was shown. A high-quality separation model for residual ADA levels for exacerbation/remission conditions for clinical and endoscopic activity for children with CD and UC was obtained through ROC-analysis. The minimum residual ADA levels for maintaining clinical remission in children with CD were 8.1 μg/mL and 10.5 μg/mL for mucosal healing. In children with UC, as well as in children weighing <40 kg, these levels were higher. The formation of antibodies to ADA was minimal; combination therapy with AZA showed no efficacy. Key cytokines correlating with ADA concentration were interleukins IL-6, -13, -31, -27, -9, and tumor necrosis factor-α. Conclusion. To improve the efficacy of ADA therapy in children with IBD, therapeutic drug monitoring should be performed, considering the nosology and body weight of the child, as well as the goal of therapy (clinical and endoscopic remission). Key words: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, adalimumab, therapeutic drug monitoring, tumor necrosis factor-α, cytokine profile, azathioprine

scholarly journals Tumour necrosis factor inhibitors in inflammatory bowel disease: the story continues

2021 ◽  
Vol 14 ◽  
pp. 175628482110599
Author(s):  
Laurent Peyrin-Biroulet ◽  
William J. Sandborn ◽  
Remo Panaccione ◽  
Eugeni Domènech ◽  
Lieven Pouillon ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tumour Necrosis Factor ◽  
Bowel Disease ◽  
Tumour Necrosis ◽  
Certolizumab Pegol ◽  
Therapeutic Drug ◽  
Tumour Necrosis Factor Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

In the 1990s, tumour necrosis factor-α inhibitor therapy ushered in the biologic therapy era for inflammatory bowel disease, leading to marked improvements in treatment options and patient outcomes. There are currently four tumour necrosis factor-α inhibitors approved as treatments for ulcerative colitis and/or Crohn’s disease: infliximab, adalimumab, golimumab and certolizumab pegol. Despite the clear benefits of tumour necrosis factor-α inhibitors, a subset of patients with inflammatory bowel disease either do not respond, experience a loss of response after initial clinical improvement or report intolerance to anti-tumour necrosis factor-α therapy. Optimizing outcomes of these agents may be achieved through earlier intervention, the use of therapeutic drug monitoring and thoughtful switching within class. To complement these approaches, evolving predictive biomarkers may help inform and optimize clinical decision making by identifying patients who might potentially benefit from an alternative treatment strategy. This review will focus on the current use of tumour necrosis factor-α inhibitors in inflammatory bowel disease and the application of personalized medicine to improve future outcomes for all patients.

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