Adding Thiopurine After Loss of Response to Infliximab Versus Early Combination in Treating Crohn's Disease: A Retrospective Study.

Adult Antimetabolites / administration & dosage Azathioprine / administration & dosage Biological Products / administration & dosage Crohn Disease / diagnosis Drug Monitoring / methods Drug Synergism Drug Therapy, Combination / adverse effects Drug-Related Side Effects and Adverse Reactions / diagnosis Female Humans Infliximab / administration & dosage Japan / epidemiology Male Mercaptopurine / administration & dosage Retrospective Studies Risk Assessment Treatment Outcome
Combination therapy Crohn’s disease Infliximab Thiopurine

Journal

Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782

Informations de publication

Date de publication:
09 2021
Historique:
received: 29 05 2020
accepted: 01 09 2020
pubmed: 14 9 2020
medline: 30 9 2021
entrez: 13 9 2020
Statut: ppublish

Résumé

Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX. This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups. One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001). Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD.

Sections du résumé

BACKGROUND
Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX.
METHODS
This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups.
RESULTS
One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001).
CONCLUSION
Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD.

Identifiants

DOI: 10.1007/s10620-020-06600-z PMID: 32920717
pubmed: 32920717
doi: 10.1007/s10620-020-06600-z
pii: 10.1007/s10620-020-06600-z
doi:

Substances chimiques

Antimetabolites 0
Biological Products 0
Infliximab B72HH48FLU
Mercaptopurine E7WED276I5
Azathioprine MRK240IY2L

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3124-3131

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Références

Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389(10080):1741–1755. https://doi.org/10.1016/S0140-6736(16)31711-1 .
doi: 10.1016/S0140-6736(16)31711-1 pubmed: 27914655
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–1549. https://doi.org/10.1016/S0140-6736(02)08512-4 .
doi: 10.1016/S0140-6736(02)08512-4 pubmed: 12047962
Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):24–30. https://doi.org/10.1016/j.autrev.2013.06.002 .
doi: 10.1016/j.autrev.2013.06.002 pubmed: 23792214
Mitrev N, Vande Casteele N, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;46(11–12):1037–1053. https://doi.org/10.1111/apt.14368 .
doi: 10.1111/apt.14368 pubmed: 29027257
Yamada A, Sono K, Hosoe N, Takada N, Suzuki Y. Monitoring functional serum antitumor necrosis factor antibody level in Crohn’s disease patients who maintained and those who lost response to anti-TNF. Inflamm Bowel Dis. 2010;16(11):1898–1904. https://doi.org/10.1002/ibd.21259 .
doi: 10.1002/ibd.21259 pubmed: 20310016
Ben-Horin S, Chowers Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nat Rev Gastroenterol Hepatol.. 2014;11(4):243–255. https://doi.org/10.1038/nrgastro.2013.253 .
doi: 10.1038/nrgastro.2013.253 pubmed: 24393836
Roda G, Jharap B, Neeraj N, Colombel JF. Loss of response to anti-TNFs: definition, epidemiology, and management. Clin Transl Gastroenterol. 2016;7:e135. https://doi.org/10.1038/ctg.2015.63 .
doi: 10.1038/ctg.2015.63 pubmed: 26741065 pmcid: 4737871
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–1395. https://doi.org/10.1056/NEJMoa0904492 .
doi: 10.1056/NEJMoa0904492 pubmed: 20393175
Levesque BG, Greenberg GR, Zou G, et al. A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn’s disease. Aliment Pharmacol Ther. 2014;39(10):1126–1135. https://doi.org/10.1111/apt.12733 .
doi: 10.1111/apt.12733 pubmed: 24689499
Bots S, Gecse K, Barclay M, D’Haens G. Combination Immunosuppression in IBD. Inflamm Bowel Dis. 2018;24(3):539–545. https://doi.org/10.1093/ibd/izx065 .
doi: 10.1093/ibd/izx065 pubmed: 29462391
Feagan BG, McDonald JW, Panaccione R, Enns RA, Bernstein CN, Ponich TP et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn’s disease. Gastroenterology. 2014;146(3):681–8 e1. https://doi.org/10.1053/j.gastro.2013.11.024 .
Moran GW, Dubeau MF, Kaplan GG, et al. Clinical predictors of thiopurine-related adverse events in Crohn’s disease. World J Gastroenterol. 2015;21(25):7795–7804. https://doi.org/10.3748/wjg.v21.i25.7795 .
doi: 10.3748/wjg.v21.i25.7795 pubmed: 26167079 pmcid: 4491966
Calafat M, Manosa M, Canete F, et al. Increased risk of thiopurine-related adverse events in elderly patients with IBD. Aliment Pharmacol Ther. 2019;50(7):780–788. https://doi.org/10.1111/apt.15458 .
doi: 10.1111/apt.15458 pubmed: 31429097
Kotlyar DS, Osterman MT, Diamond RH, Porter D, Blonski WC, Wasik M et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9(1):36–41 e1. https://doi.org/10.1016/j.cgh.2010.09.016 .
Lemaitre M, Kirchgesner J, Rudnichi A, et al. Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease. JAMA. 2017;318(17):1679–1686. https://doi.org/10.1001/jama.2017.16071 .
doi: 10.1001/jama.2017.16071 pubmed: 29114832 pmcid: 5818785
Kirchgesner J, Lemaitre M, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Risk of Serious and Opportunistic Infections Associated With Treatment of Inflammatory Bowel Diseases. Gastroenterology. 2018;155(2):337–46 e10. https://doi.org/10.1053/j.gastro.2018.04.012 .
Van Assche G, Magdelaine-Beuzelin C, D’Haens G, et al. Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology. 2008;134(7):1861–1868. https://doi.org/10.1053/j.gastro.2008.03.004 .
doi: 10.1053/j.gastro.2008.03.004 pubmed: 18440315
Bar-Yoseph H, Waterman M, Almog R, et al. Prevention of antidrug antibody formation to infliximab in Crohn’s patients with prior failure of thiopurines. Clin Gastroenterol Hepatol. 2017;15(1):69–75. https://doi.org/10.1016/j.cgh.2016.06.028 .
doi: 10.1016/j.cgh.2016.06.028 pubmed: 27404966
Mogensen DV, Brynskov J, Ainsworth MA, Nersting J, Schmiegelow K, Steenholdt C. A role for thiopurine metabolites in the synergism between thiopurines and infliximab in inflammatory bowel disease. J Crohns Colitis.. 2018;12(3):298–305. https://doi.org/10.1093/ecco-jcc/jjx149 .
doi: 10.1093/ecco-jcc/jjx149 pubmed: 29145599
Qiu Y, Mao R, Chen BL, Zhang SH, Guo J, He Y et al. Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis. Clin Gastroenterol Hepatol. 2017;15(9):1359–72 e6. https://doi.org/10.1016/j.cgh.2017.02.005 .
Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(4):444–447. https://doi.org/10.1016/j.cgh.2012.10.020 .
doi: 10.1016/j.cgh.2012.10.020 pubmed: 23103905
Ong DE, Kamm MA, Hartono JL, Lust M. Addition of thiopurines can recapture response in patients with Crohn’s disease who have lost response to anti-tumor necrosis factor monotherapy. J Gastroenterol Hepatol. 2013;28(10):1595–1599. https://doi.org/10.1111/jgh.12263 .
doi: 10.1111/jgh.12263 pubmed: 23662928
Yao T, Matsui T, Hiwatashi N. Crohn’s disease in Japan: diagnostic criteria and epidemiology. Dis Colon Rectum. 2000;43(10 Suppl):S85–S93. https://doi.org/10.1007/bf02237231 .
doi: 10.1007/bf02237231 pubmed: 11052483
Daperno M, D’Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505–512. https://doi.org/10.1016/s0016-5107(04)01878-4 .
doi: 10.1016/s0016-5107(04)01878-4 pubmed: 15472670
Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956–963. https://doi.org/10.1016/0016-5085(90)90613-6 .
doi: 10.1016/0016-5085(90)90613-6 pubmed: 2394349
Costantino G, Furfaro F, Belvedere A, Alibrandi A, Fries W. Thiopurine treatment in inflammatory bowel disease: response predictors, safety, and withdrawal in follow-up. J Crohns Colitis.. 2012;6(5):588–596. https://doi.org/10.1016/j.crohns.2011.11.007 .
doi: 10.1016/j.crohns.2011.11.007 pubmed: 22398045
van Gennep S, Konte K, Meijer B, et al. Systematic review with meta-analysis: risk factors for thiopurine-induced leukopenia in IBD. Aliment Pharmacol Ther. 2019;50(5):484–506. https://doi.org/10.1111/apt.15403 .
doi: 10.1111/apt.15403 pubmed: 31342537
Roblin X, Boschetti G, Williet N, et al. Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial. Aliment Pharmacol Ther. 2017;46(2):142–149. https://doi.org/10.1111/apt.14106 .
doi: 10.1111/apt.14106 pubmed: 28449228
Strik AS, van den Brink GR, Ponsioen C, Mathot R, Lowenberg M, D’Haens GR. Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2017;45(8):1128–1134. https://doi.org/10.1111/apt.13994 .
doi: 10.1111/apt.13994 pubmed: 28230306
Regueiro M, Feagan BG, Zou B, et al. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn’s Disease After Ileocolonic Resection. Gastroenterology. 2016;150(7):1568–1578. https://doi.org/10.1053/j.gastro.2016.02.072 .
doi: 10.1053/j.gastro.2016.02.072 pubmed: 26946343
Sakuraba A, Okamoto S, Matsuoka K, et al. Combination therapy with infliximab and thiopurine compared to infliximab monotherapy in maintaining remission of postoperative Crohn’s disease. Digestion.. 2015;91(3):233–238. https://doi.org/10.1159/000375302 .
doi: 10.1159/000375302 pubmed: 25823572
Moriyama T, Nishii R, Perez-Andreu V, et al. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet. 2016;48(4):367–373. https://doi.org/10.1038/ng.3508 .
doi: 10.1038/ng.3508 pubmed: 26878724 pmcid: 5029084
Yang SK, Hong M, Baek J, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46(9):1017–1020. https://doi.org/10.1038/ng.3060 .
doi: 10.1038/ng.3060 pubmed: 25108385 pmcid: 4999337
Kakuta Y, Naito T, Onodera M, et al. NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD. Pharmacogenomics J.. 2016;16(3):280–285. https://doi.org/10.1038/tpj.2015.43 .
doi: 10.1038/tpj.2015.43 pubmed: 26076924
Kakuta Y, Kawai Y, Okamoto D, et al. NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. J Gastroenterol. 2018;53(9):1065–1078. https://doi.org/10.1007/s00535-018-1486-7 .
doi: 10.1007/s00535-018-1486-7 pubmed: 29923122 pmcid: 6132901
Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390–9 e1. https://doi.org/10.1053/j.gastro.2012.05.004 .

Auteurs

Keizo Zeze (K)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Atsushi Hirano (A)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Takehiro Torisu (T)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. torisut@intmed2.med.kyushu-u.ac.jp.

Motohiro Esaki (M)

Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Tomohiko Moriyama (T)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Junji Umeno (J)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Keisuke Kawasaki (K)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Shin Fujioka (S)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Yuta Fuyuno (Y)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Yuichi Matsuno (Y)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Takanari Kitazono (T)

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Actions chimiques et utilisations › Actions toxiques › Noxas › Antimétabolites › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Thionucléosides › Azathioprine › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Maladie de Crohn › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Monitorage physiologique › Surveillance des médicaments › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Interactions médicamenteuses › Synergie des médicaments › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Troubles dus à des produits chimiques › Effets secondaires indésirables des médicaments › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Infliximab › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Régions géographiques › Iles › Japon › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Mercaptopurine › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Adding Thiopurine After Loss of Response to...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Adding Thiopurine After Loss of Response to...