Supratherapeutic Infliximab Levels Do Not Predict Risk of Short-term Complications in Adults With Crohn's Disease.
Journal
Journal of clinical gastroenterology
ISSN: 1539-2031
Titre abrégé: J Clin Gastroenterol
Pays: United States
ID NLM: 7910017
Informations de publication
Date de publication:
01 Jan 2023
01 Jan 2023
Historique:
received:
29
04
2021
accepted:
10
10
2021
pubmed:
16
12
2021
medline:
15
12
2022
entrez:
15
12
2021
Statut:
epublish
Résumé
It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs. We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC. Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46). In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.
Sections du résumé
BACKGROUND
BACKGROUND
It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs.
METHODS
METHODS
We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC.
RESULTS
RESULTS
Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46).
CONCLUSIONS
CONCLUSIONS
In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.
Identifiants
pubmed: 34907922
doi: 10.1097/MCG.0000000000001637
pii: 00004836-202301000-00008
doi:
Substances chimiques
Infliximab
B72HH48FLU
Gastrointestinal Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66-73Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993;30:1443–1453.
Derkx B, Taminiau J, Radema S, et al. Tumour-necrosis-factor antibody treatment in Crohn’s disease. Lancet. 1993;342:173–174.
Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114:384–413.
Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113:481–517.
Kornbluth A. Infliximab approved for use in Crohn’s disease: a report on the FDA GI Advisory Committee Conference. Inflamm Bowel Dis. 1998;4:328–329.
Kollias G, Kontoyiannis D. Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments. Cytokine Growth Factor Rev. 2002;13:315–321.
Duchet-Niedziolka P, Coutsinos Z, Hanslik T, et al. Anti-TNFalpha therapy and vaccination of adults. Joint Bone Spine. 2007;74:563–565.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT TM registry. Am J Gastroenterol. 2012;107:1409–1422.
Toruner M, Loftus EV, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929–936.
Singh S, Proudfoot JA, Dulai PS, et al. Comparative efficacy and speed of onset of action of infliximab vs golimumab in ulcerative colitis. Clin Gastroenterol Hepatol. 2019;18:424.e7–431.e7.
Hoentjen F, van Bodegraven AA. Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease. World J Gastroenterol. 2009;15:2067–2073.
Lees CW, Ali AI, Thompson AI, et al. The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther. 2009;29:286–297.
Chung ES, Packer M, Lo KH, et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α, in patients with moderate-to-severe heart failure: results of the Anti-TNF Therapy Against Congestive Heart failure (ATTACH) Trial. Circulation. 2003;107:3133–3140.
Arias MT, Vande Casteele N, Vermeire S, et al. A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2015;13:531–538.
Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am J Gastroenterol. 2009;104:760–767.
Papamichael K, Van Stappen T, Vande Casteele N, et al. Infliximab concentration thresholds during induction therapy are associated with short-term mucosal healing in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14:543–549.
Papamichael K, Chachu KA, Vajravelu RK, et al. Improved long-term outcomes of patients with inflammatory bowel disease receiving proactive compared with reactive monitoring of serum concentrations of infliximab. Clin Gastroenterol Hepatol. 2017;15:1580.e3–1588.e3.
Papamichael K, Vajravelu RK, Vaughn BP, et al. Proactive infliximab monitoring following reactive testing is associated with better clinical outcomes than reactive testing alone in patients with inflammatory bowel disease. J Crohns Colitis. 2018;12:804–810.
El-Matary W, Walters TD, Huynh HQ, et al. Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn’s disease in children. Inflamm Bowel Dis. 2019;25:150–155.
Yarur AJ, Jain A, Sussman DA, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS Study. Gut. 2016;65:249–255.
Drobne D, Kurent T, Golob S, et al. Success and safety of high infliximab trough levels in inflammatory bowel disease. Scand J Gastroenterol. 2018;53:940–946.
Landemaine A, Petitcollin A, Brochard C, et al. Cumulative exposure to infliximab, but not trough concentrations, correlate with rate of infection. Clin Gastroenterol Hepatol. 2020;19:288.e4–295.e4.
Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(suppl A):5A–36A.
Greener T, Kabakchiev B, Steinhart AH, et al. Higher infliximab levels are not associated with an increase in adverse events in inflammatory bowel disease. Inflamm Bowel Dis. 2018;24:1808–1814.
Bégaud B, Evreux JC, Jouglard J, et al. Imputation of the unexpected or toxic effects of drugs. Actualization of the method used in France. Therapie. 1985;40:111–118.
Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608.
Papamichael K, Rakowsky S, Rivera C, et al. Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis. Aliment Pharmacol Ther. 2018;47:478–484.
Plevris N, Jenkinson PW, Arnott ID, et al. Higher anti-tumor necrosis factor levels are associated with perianal fistula healing and fistula closure in Crohn’s disease. Eur J Gastroenterol Hepatol. 2020;32:32–37.
Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn’s disease. Aliment Pharmacol Ther. 2017;45:933–940.
Hendler SA, Cohen BL, Colombel J-F, et al. High-dose infliximab therapy in Crohn’s disease: clinical experience, safety, and efficacy. J Crohns Colitis. 2015;9:266–275.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT Registry. Clin Gastroenterol Hepatol. 2006;4:621–630.
Lichtenstein GR, Rutgeerts P, Sandborn WJ, et al. A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol. 2012;107:1051–1063.
Kirchgesner J, Lemaitre M, Carrat F, et al. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology. 2018;155:337.e10–346.e10.
Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011;50:124–131.
Askling J, Dixon W. The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. Curr Opin Rheumatol. 2008;20:138–144.