361
Views
0
CrossRef citations to date
0
Altmetric
Review

Efficacious dosing regimens for anti-TNF therapies in inflammatory bowel disease: where do we stand?

ORCID Icon, ORCID Icon & ORCID Icon
Pages 341-351 | Received 23 Jan 2023, Accepted 29 Mar 2023, Published online: 09 Apr 2023

References

  • Derkx B, Taminiau J, Radema S, et al. Tumour-necrosis-factor antibody treatment in Crohn’s disease. Lancet. 1993 Jul 17;342(8864):173–174.
  • van Dullemen HM, van Deventer SJ, Hommes DW, et al. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995 Jul;109(1):129–135.
  • Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 study group. N Engl J Med. 1997 Oct 9;337(15):1029–1035. DOI:10.1056/NEJM199710093371502
  • Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet. 2002 May 4;359(9317):1541–1549. DOI:10.1016/S0140-6736(02)08512-4
  • Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 26;350(9):876–885.
  • Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462–2476.
  • Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006 Feb;130(2):323–333. quiz 591. DOI:10.1053/j.gastro.2005.11.030
  • Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52–65.
  • Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn's disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):829–838.
  • D’haens GR, Sandborn WJ, Loftus EV Jr., et al. Higher vs standard adalimumab induction dosing regimens and two maintenance strategies: randomized SERENE CD trial results. Gastroenterology. 2022 Jun;162(7):1876–1890. DOI:10.1053/j.gastro.2022.01.044
  • 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):1232–1239.
  • Colombel JF, Sandborn WJ, Rutgeerts P, et al. Comparison of two adalimumab treatment schedule strategies for moderate-to-severe Crohn’s disease: results from the CHARM trial. Am J Gastroenterol. 2009 May;104(5):1170–1179.
  • Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102–1111 e2.
  • Colombel JF, Schwartz DA, Sandborn WJ, et al. Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut. 2009 Jul;58(7):940–948.
  • Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomized controlled trial. Gut. 2011 Jun;60(6):780–787.
  • Panes J, Colombel JF, D’haens GR, et al. Higher vs standard adalimumab induction and maintenance dosing regimens for treatment of ulcerative colitis: sERENE UC trial results. Gastroenterology. 2022 Jun;162(7):1891–1910.
  • Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012 Feb;142(2):257–265.
  • Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007 Jul 19;357(3):228–238.
  • Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007 Jul 19;357(3):239–250.
  • Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85–95. quiz e14-5. DOI:10.1053/j.gastro.2013.05.048
  • Probert CS, Sebastian S, Gaya DR, et al. Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis). BMJ Open Gastroenterol. 2018;5(1):e000212. DOI:10.1136/bmjgast-2018-000212
  • Taxonera C, Iborra M, Bosca-Watts MM, et al. Early dose optimization of golimumab induces late response and long-term clinical benefit in moderately to severely active ulcerative colitis. Curr Med Res Opin. 2019 Jul;35(7):1297–1304.
  • Berends SE, Strik AS, Jansen JM, et al. Pharmacokinetics of golimumab in moderate to severe ulcerative colitis: the GO-KINETIC study. Scand J Gastroenterol. 2019 Jun;54(6):700–706.
  • Schultheiss JPD, Mahmoud R, Louwers JM, et al. Loss of response to anti-TNFα agents depends on treatment duration in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2021 Nov;54(10):1298–1308.
  • Qiu Y, Chen BL, Mao R, et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease. J Gastroenterol. 2017 May;52(5):535–554.
  • Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019 May;4(5):341–353.
  • 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 Feb 13;348(7):601–608.
  • Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009 Nov;137(5):1628–1640.
  • Vande Casteele N, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015 Oct;64(10):1539–1545.
  • Sazonovs A, Kennedy NA, Moutsianas L, et al. HLA-DQA1*05 Carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with crohn’s disease. Gastroenterology. 2020 Jan;158(1):189–199.
  • Vaisman-Mentesh A, Gutierrez-Gonzalez M, DeKosky BJ, et al. The molecular mechanisms that underlie the immune biology of anti-drug antibody formation following treatment with monoclonal antibodies. Front Immunol. 2020;11:1951.
  • 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):1258–1264.
  • Bots SJ, Parker CE, Brandse JF, et al. Anti-drug antibody formation against biologic agents in inflammatory bowel disease: a systematic review and meta-analysis. BioDrugs. 2021 Nov;35(6):715–733. DOI:10.1007/s40259-021-00507-5
  • Seow CH, Newman A, Irwin SP, et al. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010 Jan;59(1):49–54.
  • Roblin X, Marotte H, Rinaudo M, et al. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014 Jan;12(1):80–84 e2.
  • Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019 Aug;17(9):1655–1668.e3. DOI:10.1016/j.cgh.2019.03.037
  • Imaeda H, Takahashi K, Fujimoto T, et al. Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohn’s disease. J Gastroenterol. 2014 Jan;49(1):100–109.
  • 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 Apr;45(7):933–940.
  • Reinisch W, Colombel JF, Sandborn WJ, et al. Factors associated with short- and long-term outcomes of therapy for Crohn’s disease. Clin Gastroenterol Hepatol. 2015 Mar;13(3):539–547.e2.
  • Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014 Nov;63(11):1721–1727.
  • Gonczi L, Vegh Z, Golovics PA, et al. Prediction of short- and medium-term efficacy of biosimilar infliximab therapy. do trough levels and antidrug antibody levels or clinical and biochemical markers play the more important role? J Crohns Colitis. 2017 Jun 1;11(6):697–705.
  • Barclay ML, Karim S, Helms ETJ, et al. Infliximab and adalimumab concentrations and anti-drug antibodies in inflammatory bowel disease control using New Zealand assays. Intern Med J. 2019 Apr;49(4):513–518.
  • Singh N, Rosenthal CJ, Melmed GY, et al. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014 Oct;20(10):1708–1713.
  • Ward MG, Warner B, Unsworth N, et al. Infliximab and adalimumab drug levels in Crohn’s disease: contrasting associations with disease activity and influencing factors. Aliment Pharmacol Ther. 2017 Jul;46(2):150–161.
  • Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of induction infliximab levels with clinical response in perianal crohn’s disease. J Crohns Colitis. 2017 May 1;11(5):549–555.
  • van Hoeve K, Dreesen E, Hoffman I, et al. Higher infliximab trough levels are associated with better outcome in paediatric patients with inflammatory bowel disease. J Crohns Colitis. 2018 Nov 15;12(11):1316–1325.
  • Papamichael K, Rakowsky S, Rivera C, et al. Association between serum infliximab trough concentrations during maintenance therapy and biochemical, endoscopic, and histologic remission in crohn’s disease. Inflamm Bowel Dis. 2018 Sep 15;24(10):2266–2271.
  • Dreesen E, D’haens G, Baert F. Infliximab exposure predicts superior endoscopic outcomes in patients with active crohn’s disease: pharmacokinetic–pharmacodynamic analysis of TAILORIX. J Crohns Colitis. 2018;12:S063–064.
  • Yarur AJ, Kubiliun MJ, Czul F, et al. Concentrations of 6-thioguanine nucleotide correlate with trough levels of infliximab in patients with inflammatory bowel disease on combination therapy. Clin Gastroenterol Hepatol. 2015 Jun;13(6):1118–24.e3.
  • 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. 2016 Apr;14(4):550–557 e2.
  • 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 Apr;14(4):543–549.
  • Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014 Dec;147(6):1296–1307.e5.
  • Marits P, Landucci L, Sundin U, et al. Trough s-infliximab and antibodies towards infliximab in a cohort of 79 IBD patients with maintenance infliximab treatment. J Crohns Colitis. 2014 Aug;8(8):881–889.
  • Roblin X, Boschetti G, Duru G, et al. Distinct thresholds of infliximab trough level are associated with different therapeutic outcomes in patients with inflammatory bowel disease: a prospective observational study. Inflamm Bowel Dis. 2017 Nov;23(11):2048–2053.
  • Kobayashi T, Suzuki Y, Motoya S, et al. First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis. J Gastroenterol. 2016 Mar;51(3):241–251.
  • 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 Feb;47(4):478–484.
  • Mattoo VY, Basnayake C, Connell WR, et al. Systematic review: efficacy of escalated maintenance anti-tumour necrosis factor therapy in Crohn’s disease. Aliment Pharmacol Ther. 2021 Aug;54(3):249–266.
  • Ma C, Huang V, Fedorak DK, et al. Adalimumab dose escalation is effective for managing secondary loss of response in Crohn’s disease. Aliment Pharmacol Ther. 2014 Nov;40(9):1044–1055.
  • Afif W, Loftus EV Jr., Faubion WA, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010 May;105(5):1133–1139.
  • Steenholdt C, Bendtzen K, Brynskov J, et al. Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn’s disease. J Crohns Colitis. 2015 Mar;9(3):238–245.
  • Srinivasan A, Vasudevan A, McFarlane A, et al. Anti-TNF re-induction is as effective, simpler, and cheaper compared with dose interval shortening for secondary loss of response in Crohn’s Disease. J Crohns Colitis. 2018 Feb 28;12(3):280–288.
  • Battat R, Lukin D, Scherl EJ, et al. Immunogenicity of tumor necrosis factor antagonists and effect of dose escalation on anti-drug antibodies and serum drug concentrations in inflammatory bowel disease. Inflamm Bowel Dis. 2021 Aug 19;27(9):1443–1451.
  • Assa A, Matar M, Turner D, et al. Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with crohn’s disease compared with reactive monitoring. Gastroenterology. 2019 Oct;157(4):985–996 e2.
  • Papamichael K, Juncadella A, Wong D, et al. Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared with standard of care in patients with inflammatory bowel disease. J Crohns Colitis. 2019 Aug 14;13(8):976–981.
  • Fernandes SR, Serrazina J, Rodrigues IC, et al. Proactive therapeutic drug monitoring is more effective than conventional management in inducing fecal calprotectin remission in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2021 Dec 1;33(12):1539–1546.
  • Fernandes SR, Bernardo S, Simões C, et al. Proactive infliximab drug monitoring is superior to conventional management in inflammatory bowel disease. Inflamm Bowel Dis. 2020 Jan 6;26(2):263–270.
  • 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 Jun 28;12(7):804–810.
  • Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015 Jun;148(7):1320–9.e3.
  • Strik AS, Löwenberg M, Mould DR, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021 Feb;56(2):145–154.
  • D’haens G, Vermeire S, Lambrecht G, et al. Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, and corticosteroid-free remission in patients with active luminal crohn’s disease. Gastroenterology. 2018 Apr;154(5):1343–1351.e1.
  • Strik AS, van den Brink GR, Ponsioen C, et al. 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 Apr;45(8):1128–1134.
  • 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 Apr;11(4):444–447.
  • Ungar B, Kopylov U, Engel T, et al. Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab. Aliment Pharmacol Ther. 2017 Jan;45(2):276–282.
  • 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):1383–1395.
  • 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.
  • Vermeire S, Noman M, Van Assche G, et al. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007 Sep;56(9):1226–1231.
  • Colombel JF, Adedokun OJ, Gasink C, et al. Combination therapy with infliximab and azathioprine improves infliximab pharmacokinetic features and efficacy: a post hoc analysis. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1525–1532.e1.
  • Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomized controlled trial. Lancet. 2015 Nov 7;386(10006):1825–1834.
  • Colombel JF, Panaccione R, Bossuyt P, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomized, controlled phase 3 trial. Lancet. 2017 Dec 23;390(10114):2779–2789.
  • Matsumoto T, Motoya S, Watanabe K, et al. Adalimumab monotherapy and a combination with azathioprine for crohn’s disease: a prospective, randomized trial. J Crohns Colitis. 2016 Nov;10(11):1259–1266.
  • Watanabe K, Matsumoto T, Hisamatsu T, et al. Clinical and pharmacokinetic factors associated with adalimumab-induced mucosal healing in patients with crohn’s disease. Clin Gastroenterol Hepatol. 2018 Apr;16(4):542–549 e1.
  • Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in crohn’s disease: medical treatment. J Crohns Colitis. 2020 Jan 1;14(1):4–22.
  • Beaugerie L, Kirchgesner J. Balancing benefit vs risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019 Feb;17(3):370–379.
  • 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 Jun;134(7):1861–1868.
  • Louis JE, Resche-Rigon M, Laharie D, et al. OP01 Withdrawal of infliximab or anti-metabolite therapy in Crohn’s Disease patients in sustained remission on combination therapy: a randomized unblinded controlled trial (SPARE). J Crohn’s Colitis. 2022;16(Supplement_1):i001. DOI:10.1093/ecco-jcc/jjab232.000
  • Pierre N, Huynh-Thu VA, Marichal T, et al. Distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn’s disease stopping infliximab: when the remission state hides different types of residual disease activity. Gut. 2022 Aug 25;72:443–450.
  • Roblin X, Boschetti G, Williet N, et al. Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomized clinical trial. Aliment Pharmacol Ther. 2017 Jul;46(2):142–149.
  • Borren NZ, Luther J, Colizzo FP, et al. Low-dose methotrexate has similar outcomes to high-dose methotrexate in combination with anti-TNF Therapy in inflammatory bowel diseases. J Crohns Colitis. 2019 Aug 14;13(8):990–995.
  • Colman RJ, Rubin DT. Optimal doses of methotrexate combined with anti-TNF therapy to maintain clinical remission in inflammatory bowel disease. J Crohns Colitis. 2015 Apr;9(4):312–317.
  • Roblin X, Vérot C, Paul S, et al. Is the pharmacokinetic profile of a first anti-TNF predictive of the clinical outcome and pharmacokinetics of a second anti-TNF? Inflamm Bowel Dis. 2018 Aug 16;24(9):2078–2085.
  • Roblin X, Williet N, Boschetti G, et al. Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomized trial. Gut. 2020 Jul;69(7):1206–1212.
  • Schreiber S, Ben-Horin S, Leszczyszyn J, et al. Randomized Controlled trial: subcutaneous vs intravenous infliximab CT-P13 maintenance in inflammatory bowel disease. Gastroenterology. 2021 Jun;160(7):2340–2353.
  • Buisson A, Nachury M, Reymond M, et al. Effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases: the REMSWITCH study. Clin Gastroenterol Hepatol. 2022 Aug 17. DOI:10.1016/j.cgh.2022.08.011

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.