8th March 2019,
Afrasyab Khan, Arvenia B Berahmana, Andrew S Day, Murray L Barclay, Michael Schultz
The incidence of inflammatory bowel disease (IBD) in New Zealand has risen substantially in the last five decades.1–6 IBD comprises Crohn’s disease (CD) and ulcerative colitis (UC) with a small…
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Various medications are available for the treatment of inflammatory bowel disease. The effective use of these medications is important and leads to better outcomes. Monitoring the level of medications and/or their breakdown products (therapeutic drug monitoring) in a patient’s blood can lead to more effective and individualised dosage recommendations. These blood tests are available in New Zealand. Therapeutic drug monitoring can decrease the risk of drug toxicity and help in decision making for further treatment if one therapy seems to be failing. This document represents the New Zealand Society of Gastroenterology Guidelines on Therapeutic Drug Monitoring in Inflammatory Bowel Disease.
The incidence of inflammatory bowel disease (IBD) in New Zealand has increased over the last several decades. The management of IBD has been transformed since the introduction of monoclonal antibody drugs. Other medications used in the treatment of IBD include amino-salicylates, steroids, thiopurines and methotrexate. Therapeutic drug monitoring (TDM) involves the measurement of serum drug levels or active metabolites and anti-drug antibodies. TDM is essential for a personalised approach to the management of patients with IBD and is used to optimise drug efficacy and reduce the risk of toxicity. In IBD, TDM can be used for checking adherence, evaluating drug toxicity, identifying hypermethylators, assessing loss of response and in decisions regarding treatment escalation or de-escalation. Management decisions in patients on a thiopurine are facilitated by checking TPMT enzyme activity and thiopurine metabolite levels. Measurement of drug trough levels and anti-drug antibodies can result in individualised treatment decisions in patients on biologics. In addition to using TDM in patients who fail therapy, proactive TDM can potentially facilitate early treatment decisions, albeit more work is needed in this area. The clinical benefits of reactive TDM are well documented and this has been shown to be cost effective. Studies have shown that combination therapy in patients on a biologic leads to better clinical outcomes. Effective use of drugs in the treatment of IBD is even more imperative in the New Zealand setting due to relatively fewer options of funded treatment, and the limitations on the use of available drugs. This document represents the current guidelines of the New Zealand Society of Gastroenterology on TDM in IBD.
- Eason RJ, Lee SP, Tasman-Jones C. Inflammatory bowel disease in Auckland, New Zealand. Aust N Z Med J. 1982 Apr; 12(2):125–31.
- Schlup M, Maclaurin BP, Barbezat GO, de Lambert BM. Crohn’s disease: a ten year retrospective review at Dunedin hospitals. N Z Med J. 1986 Mar 12; 99(797):141–4.
- Wigley R, Maclaurin BP. A study of ulcerative colitis in New Zealand, showing a low incidence in Maoris. Br Med J. 1962 Jul 28; 2(5299):228–31.
- Su HY, Gupta V, Day AS, Gearry RB. Rising Incidence of Inflammatory Bowel Disease in Canterbury, New Zealand. Inflamm Bowel Dis. 2016 Sep; 22(9):2238–44.
- Gearry RB, Day AS. Inflammatory bowel disease in New Zealand children--a growing problem. N Z Med J. 2008 Oct 3; 121(1283):5–8.
- Coppell K, Galts C, Huizing F, et al. Annual Incidence and Phenotypic Presentation of IBD in Southern New Zealand: An 18-Year Epidemiological Analysis. Inflamm Intest Dis. 2018 Sep 17.
- Stidham RW, Higgins PDR. Colorectal Cancer in Inflammatory Bowel Disease. Clin Colon Rectal Surg. 2018 May; 31(3):168–78.
- Baek S-J, Kim S-H. Colitis-associated colorectal cancer in patients with inflammatory bowel disease. Minerva Chir. 2017 Dec; 72(6):520–9.
- Chan HC-H, Ng SC. Emerging biologics in inflammatory bowel disease. J Gastroenterol. 2017 Feb; 52(2):141–50.
- 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 Dec; 46(11–12):1037–53.
- Vande Casteele N, Herfarth H, Katz J, et al. American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases. Gastroenterology. 2017 Sep; 153(3):835–857.e6.
- Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology. 2017 Sep; 153(3):827–34.
- Bots S, Gecse K, Barclay M, D’Haens G. Combination Immunosuppression in IBD. Inflamm Bowel Dis. 2018 Feb 15; 24(3):539–45.
- Ding NS, Hart A, De Cruz P. Systematic review: predicting and optimising response to anti-TNF therapy in Crohn’s disease - algorithm for practical management. Aliment Pharmacol Ther. 2016 Jan; 43(1):30–51.
- Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in Inflammatory Bowel Disease. J Crohns Colitis. 2018 Aug 23.
- Gisbert JP, Nino P, Cara C, Rodrigo L. Comparative effectiveness of azathioprine in Crohn’s disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients. Aliment Pharmacol Ther. 2008 Jul; 28(2):228–38.
- van Asseldonk DP, Sanderson J, de Boer NKH, et al. Difficulties and possibilities with thiopurine therapy in inflammatory bowel disease--proceedings of the first Thiopurine Task Force meeting. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2011 Apr; 43(4):270–6.
- Gearry RB, Barclay ML, Burt MJ, et al. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol Drug Saf. 2004 Aug; 13(8):563–7.
- Simsek M, Meijer B, Ramsoekh D, et al. Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2018 Jun 1.
- Subramaniam K, D’Rozario J, Pavli P. Lymphoma and other lymphoproliferative disorders in inflammatory bowel disease: a review. J Gastroenterol Hepatol. 2013 Jan; 28(1):24–30.
- Kotlyar DS, Lewis JD, Beaugerie L, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2015 May; 13(5):847–858.e4; quiz e48–50.
- Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology. 2011 Nov; 141(5):1621–1628.e1–5.
- Seksik P, Mary J-Y, Beaugerie L, et al. Incidence of nodular regenerative hyperplasia in inflammatory bowel disease patients treated with azathioprine. Inflamm Bowel Dis. 2011 Feb; 17(2):565–72.
- Qiu Y, Mao R, Zhang S, et al. Safety Profile of Thiopurines in Crohn Disease: Analysis of 893 Patient-Years Follow-Up in a Southern China Cohort. Medicine (Baltimore). 2015 Oct; 94(41):e1513.
- Moran GW, Dubeau M-F, Kaplan GG, et al. Clinical predictors of thiopurine-related adverse events in Crohn’s disease. World J Gastroenterol. 2015 Jul 7; 21(25):7795–804.
- Bahi M, Walmsley RS, Gray AR, et al. The risk of non-melanoma skin cancer in New Zealand in inflammatory bowel disease patients treated with thiopurines. J Gastroenterol Hepatol. 2018 May; 33(5):1047–52.
- Sayani FA, Prosser C, Bailey RJ, et al. Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events. Can J Gastroenterol J Can Gastroenterol. 2005 Mar; 19(3):147–51.
- Newman WG, Payne K, Tricker K, et al. A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics. 2011 Jun; 12(6):815–26.
- Cheung S-T, Allan RN. Mistaken identity: misclassification of TPMT phenotype following blood transfusion. Eur J Gastroenterol Hepatol. 2003 Nov;15(11):1245–7.
- Donnan JR, Ungar WJ, Mathews M, Rahman P. Systematic review of thiopurine methyltransferase genotype and enzymatic testing strategies. Ther Drug Monit. 2011 Apr; 33(2):192–9.
- Gardiner SJ, Gearry RB, Begg EJ, et al. Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2008 Jun; 6(6):654–60; quiz 604.
- Mulder C. Personal communication with Prof Chris Mulder, Department of Gastroenterology and Hepatology, Vrije Universiteit Medical Center, 1081 HV Amsterdam, The Netherlands. 2018.
- van Asseldonk DP, Jharap B, Verheij J, et al. The Prevalence of Nodular Regenerative Hyperplasia in Inflammatory Bowel Disease Patients Treated with Thioguanine Is Not Associated with Clinically Significant Liver Disease. Inflamm Bowel Dis. 2016 Sep; 22(9):2112–20.
- Dubinsky MC, Vasiliauskas EA, Singh H, et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology. 2003 Aug; 125(2):298–303.
- Seidman EG. Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD. Rev Gastroenterol Disord. 2003; 3 Suppl 1:S30-38.
- Spencer EA, Dubinsky MC. Therapeutic Drug Monitoring in Inflammatory Bowel Disease: History and Future Directions. Pediatr Clin North Am. 2017 Dec; 64(6):1309–26.
- Beswick L, Friedman AB, Sparrow MP. The role of thiopurine metabolite monitoring in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2014 May; 8(4):383–92.
- Cappello M, Morreale GC. The Role of Laboratory Tests in Crohn’s Disease. Clin Med Insights Gastroenterol. 2016; 9:51–62.
- Meijer B, Mulder CJ, van Bodegraven AA, de Boer NKH. How I treat my inflammatory bowel disease-patients with thiopurines? World J Gastrointest Pharmacol Ther. 2016 Nov 6; 7(4):524–30.
- Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology. 2006 Apr; 130(4):1047–53.
- Andoh A, Tsujikawa T, Ban H, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2008 Sep; 23(9):1373–7.
- Lim SZ, Chua EW. Revisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring. Front Pharmacol. 2018; 9:1107.
- Gilissen LPL, Wong DR, Engels LGJB, et al. Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy. J Crohns Colitis. 2012 Jul; 6(6):698–707.
- Stocco G, Londero M, Campanozzi A, et al. Usefulness of the measurement of azathioprine metabolites in the assessment of non-adherence. J Crohns Colitis. 2010 Nov; 4(5):599–602.
- Dubinsky M, Lamothe S, Yang T, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000; 118(4):705–13.
- Meijer B, Kreijne JE, van Moorsel SAW, et al. 6-methylmercaptopurine-induced leukocytopenia during thiopurine therapy in inflammatory bowel disease patients. J Gastroenterol Hepatol. 2017 Jun; 32(6):1183–90.
- Amin J, Huang B, Yoon J, Shih DQ. Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD. Inflamm Bowel Dis. 2015 Feb; 21(2):445–52.
- Beswick L, Hair CS, Dowling D. Letter: successful mercaptopurine therapy after azathioprine-related pancreatitis in patients with IBD. Aliment Pharmacol Ther. 2013 Jan; 37(1):162.
- Gallego-Gutierrez S, Navas-Lopez VM, Kolorz M, Bartosova L, et al. Successful Mercaptopurine Usage despite Azathioprine-Induced Pancreatitis in Paediatric Crohn’s Disease. J Crohns Colitis. 2015 Aug; 9(8):676–9.
- Bonaz B, Boitard J, Marteau P, et al. Tioguanine in patients with Crohn’s disease intolerant or resistant to azathioprine/mercaptopurine. Aliment Pharmacol Ther. 2003 Aug 15; 18(4):401–8.
- van Egmond R, Chin P, Zhang M, et al. High TPMT enzyme activity does not explain drug resistance due to preferential. Aliment Pharmacol Ther. 2012 May; 35(10):1181–9.
- Ansari A, Patel N, Sanderson J, et al. Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2010 Mar; 31(6):640–7.
- Ansari A, Elliott T, Baburajan B, et al. Long-term outcome of using allopurinol co-therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease. Aliment Pharmacol Ther. 2008 Sep 15; 28(6):734–41.
- Blaker PA, Arenas-Hernandez M, Smith MA, et al. Mechanism of allopurinol induced TPMT inhibition. Biochem Pharmacol. 2013 Aug 15; 86(4):539–47.
- van Schie KA, Ooijevaar-de Heer P, et al. Therapeutic TNF Inhibitors can Differentially Stabilize Trimeric TNF by Inhibiting Monomer Exchange. Sci Rep. 2016 Sep 8; 6:32747.
- Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn’s disease. Aliment Pharmacol Ther. 2011 May; 33(9):987–95.
- Roda G, Jharap B, Neeraj N, Colombel J-F. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol. 2016 Jan 7; 7:e135.
- Ford AC, Sandborn WJ, Khan KJ, et al. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr; 106(4):644–59, quiz 660.
- Ungar B, Anafy A, Yanai H, et al. Significance of low level infliximab in the absence of anti-infliximab antibodies. World J Gastroenterol. 2015 Feb 14; 21(6):1907–14.
- Vande Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol. 2013 Jun; 108(6):962–71.
- Yanai H, Lichtenstein L, Assa A, et al. Levels of drug and antidrug antibodies are associated with outcome of interventions after loss of response to infliximab or adalimumab. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2015 Mar; 13(3):522-530.e2.
- Personal Communication with Canterbury Health Laboratories, Christchurch, New Zealand. 2018.
- Lopetuso LR, Gerardi V, Papa V, et al. Can We Predict the Efficacy of Anti-TNF-alpha Agents? Int J Mol Sci. 2017 Sep 14; 18(9).
- Brandse JF, Mathot RA, van der Kleij D, et al. Pharmacokinetic Features and Presence of Antidrug Antibodies Associate With Response to Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2016 Feb; 14(2):251–258.e1–2.
- 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 Off Clin Pract J Am Gastroenterol Assoc. 2017 Oct;15(10):1580–1588.e3.
- Mitchell RA, Shuster C, Shahidi N, et al. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience. Can J Gastroenterol Hepatol. 2016; 2016:5203898.
- Armuzzi A, Felice C. IBD: Infliximab dose optimization in IBD-proactive or reactive? Nat Rev Gastroenterol Hepatol. 2014 Dec; 11(12):706–8.
- Vaughn BP, Martinez-Vazquez M, Patwardhan VR, et al. Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study. Inflamm Bowel Dis. 2014 Nov; 20(11):1996–2003.
- OP029. Drug-concentration versus symptom-driven dose adaptation of Infliximab in patients with active Crohn’s disease: a prospective, randomised, multicentre trial (Tailorix). J Crohns Colitis. 2016 Mar 1; 10(suppl_1):S24–S24.
- Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. 2015 Jun; 148.
- Ben-Horin S. Drug Level-based Anti-Tumor Necrosis Factor Therapy: Ready for Prime Time? Gastroenterology. 2015 Jun; 148(7):1268–71.
- Ben-Horin S, Chowers Y, Ungar B, et al. Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal. Aliment Pharmacol Ther. 2015 Aug; 42(3):356–64.
- Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun; 63(6):919–27.
- Ungar B, Levy I, Yavne Y, et al. Optimizing Anti-TNF-alpha Therapy: Serum Levels of Infliximab and Adalimumab Are Associated with Mucosal Healing in Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2016 Apr;1 4(4):550-557.e2.
- Roblin X, Rinaudo M, Del Tedesco E, et al. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am J Gastroenterol. 2014 Aug; 109(8):1250–6.
- Teruel C, Garrido E, Mesonero F. Diagnosis and management of functional symptoms in inflammatory bowel disease in remission. World J Gastrointest Pharmacol Ther. 2016 Feb 6; 7(1):78–90.
- Piche T, Ducrotte P, Sabate JM, et al. Impact of functional bowel symptoms on quality of life and fatigue in quiescent Crohn disease and irritable bowel syndrome. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2010 Jun; 22(6):626–e174.
- Jonefjall B, Strid H, Ohman L, et al. Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2013 Sep; 25(9):756–e578.
- Vivinus-Nebot M, Frin-Mathy G, Bzioueche H, et al. Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut. 2014 May; 63(5):744–52.
- Fukuba N, Ishihara S, Tada Y, et al. Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission: prospective multicenter study. Scand J Gastroenterol. 2014 Jun; 49(6):674–80.
- Ungar B, Chowers Y, Yavzori M, et al. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut. 2014 Aug; 63(8):1258–64.
- Strik AS, Bots SJA, D’Haens G, Lowenberg M. Optimization of anti-TNF therapy in patients with Inflammatory Bowel Disease. Expert Rev Clin Pharmacol. 2016; 9(3):429–39.
- Pharmaceutical Management Agency (PHARMAC). Form RS1581. [Internet]. 2019 [cited 2019 Jan 4]. Available from: http://www.pharmac.govt.nz/2019/01/01/RS1581.pdf
- Pharmaceutical Management Agency (PHARMAC). Form SA1621. [Internet]. 2018 [cited 2019 Jan 4]. Available from:
- European Medicines Agency. Guideline on bioanalytical method validation. Eur Med Agency Lond. 2009;
- Bodini G, Giannini EG, Furnari M, et al. Comparison of Two Different Techniques to Assess Adalimumab Trough Levels in Patients with Crohn’s Disease. J Gastrointest Liver Dis JGLD. 2015 Dec; 24(4):451–6.
- Vaughn BP, Sandborn WJ, Cheifetz AS. Biologic concentration testing in inflammatory bowel disease. Inflamm Bowel Dis. 2015 Jun; 21(6):1435–42.
- Restellini S, Bessissow T, Lemieux C, et al. P711 A pilot study using point of care testing for infliximab and faecal calprotectin in IBD patients with a secondary loss of response. J Crohns Colitis. 2018 Jan 16; 12(supplement_1):S470–1.
- Ametzazurra A, Rivera N, Hernández AM, et al. Rapid Point-of-Care Monitoring of Anti-Infliximab Antibodies in Patients with Inflammatory Bowel Disease Treated with the Reference Infliximab or CT-P13 in Routine Clinical Practice. Gastroenterology. 2017 Apr 1; 152(5):S391.
- 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 Off Clin Pract J Am Gastroenterol Assoc. 2013 Apr; 11(4):444–7.
- Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010 Apr 15; 362(15):1383–95.
- Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014 Feb; 146(2):392-400.e3.
- 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 Jul; 107(7):1051–63.
- Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007 Sep; 56(9):1232–9.
- Chalhoub JM, Rimmani HH, Gumaste VV, Sharara AI. Systematic Review and Meta-analysis: Adalimumab Monotherapy Versus Combination Therapy with Immunomodulators for Induction and Maintenance of Remission and Response in Patients with Crohn’s Disease. Inflamm Bowel Dis. 2017 Aug; 23(8):1316–27.
- Zator ZA, Regueiro M, Goldby-Reffner K, et al. Sa1961 Low-dose Concomitant Azathioprine is as Effective as High-dose Azathioprine in Preventing Immunogenicity to Infliximab. Gastroenterology. 2018 Feb 15; 150(4):S417.
- 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 Off Clin Pract J Am Gastroenterol Assoc. 2017 Jan; 15(1):69–75.
- D’Haens G, Reinisch W, Colombel J-F, et al. Five-year Safety Data From ENCORE, a European Observational Safety Registry for Adults with Crohn’s Disease Treated with Infliximab [Remicade(R)] or Conventional Therapy. J Crohns Colitis. 2017 Jun 1; 11(6):680–9.
- Steiner S. Clinical Outcomes of Methotrexate Binary treatment with INfliximab or adalimumab in practicE [Internet]. 2015. Available from: http://www.improvecarenow.org/the_combine_study
- Day AS, Gulati AS, Patel N, et al. The Role of Combination Therapy in Pediatric Inflammatory Bowel Disease: A Clinical Report from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):361–8.
- Gupta N, Bostrom AG, Kirschner BS, et al. Incidence of stricturing and penetrating complications of Crohn’s disease diagnosed in pediatric patients. Inflamm Bowel Dis. 2010 Apr; 16(4):638–44.
- Martelli L, Olivera P, Roblin X, et al. Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review. J Gastroenterol. 2017 Jan 1; 52(1):19–25.
- Ricciuto A, Dhaliwal J, Walters TD, et al. Clinical Outcomes with Therapeutic Drug Monitoring in Inflammatory Bowel Disease: A Systematic Review With Meta-Analysis. J Crohns Colitis. 2018 Nov 15; 12(11):1302–15.
- Bressler B, Marshall JK, Bernstein CN, et al. Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus. Gastroenterology. 2015 May 1; 148(5):1035–1058.e3.
- Giráldez J, Ferreiro R, López JG, et al. GM-032 Economic impact of adalimumab monitoring through algorithm use in patients with inflammatory bowel disease. Eur J Hosp Pharm. 2017 Mar 1; 24(Suppl 1):A171.
- Dean L. Thioguanine Therapy and TPMT Genotype. In: Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B, Malheiro A, editors. Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
- Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui C-H, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clin Pharmacol Ther. 2018.
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