Optimizing adalimumab therapies using therapeutic drug monitoring: current evidence and future perspectives_Chinese Journal of Evidence-Based Medicine

Authors：

DING Xiaoliang ^1,2,3 ,  MIAO Liyan ^1,2,3

1. Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China;
2. College of Pharmaceutical Sciences, Soochow University, Suzhou 215100, P. R. China;
3. Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou 215006, P. R. China;

Corresponding author：

MIAO Liyan, Email: miaolysuzhou@163.com

Keywords：

Therapeutic drug monitoring; Adalimumab; Rheumatoid arthritis; Ankylosing spondylitis; Crohn’s disease; Psoriasis

DOI：

10.7507/1672-2531.202208123

Video：

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Abstract Full text Figures/Tables Video References Cited by

Therapeutic drug monitoring (TDM) has been more widely used in small molecule agents, such as immuno-suppressants, antiepileptic drugs and antibiotics, with less attention in the field of therapeutic biological agents. Monoclonal drugs represented by tumor necrosis factor alpha (TNF-α) inhibitors have shown a good relationship between exposure and efficacy in clinical studies. There are corresponding guidelines and consensus for the recommendations of TDM based on current research evidence. Therefore, this paper introduced the current evidence, strategies and considerations for TDM in the optimal treatment of adalimumab from the perspective of adalimumab TDM to provide references for the clinical practice of adalimumab TDM.

Citation： DING Xiaoliang, MIAO Liyan. Optimizing adalimumab therapies using therapeutic drug monitoring: current evidence and future perspectives. Chinese Journal of Evidence-Based Medicine, 2023, 23(1): 85-93. doi: 10.7507/1672-2531.202208123 Copy

1.	U. S. Food & Drug Administration. Label for HUMIRA^® (adalimumab) injection. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125057s417lbl.pdf.
2.	Papamichael K, Afif W, Drobne D, et al. Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives. Lancet Gastroenterol Hepatol, 2022, 7(2): 171-185.
3.	Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology, 2017, 153(3): 827-834.
4.	Mitrev N, Vande CN, 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.
5.	Cheifetz AS, Abreu MT, Afif W, et al. A comprehensive literature review and expert consensus statement on therapeutic drug monitoring of biologics in inflammatory bowel disease. Am J Gastroenterol, 2021, 116(10): 2014-2025.
6.	Irving PM, Gecse KB. Optimizing therapies using therapeutic drug monitoring: current strategies and future perspectives. Gastroenterology, 2022, 162(5): 1512-1524.
7.	Khan A, Berahmana AB, Day AS, et al. New Zealand Society of Gastroenterology Guidelines on therapeutic drug Monitoring in inflammatory bowel disease. N Z Med J, 2019, 132(1491): 46-62.
8.	Melmed GY, Irving PM, Jones J, et al. Appropriateness of testing for anti-tumor necrosis factor agent and antibody concentrations, and interpretation of results. Clin Gastroenterol Hepatol, 2016, 14(9): 1302-1309.
9.	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, 17(9): 1655-1668.
10.	Krieckaert CL, van Tubergen A, Gehin JE, et al. EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis, 2022. DOI: 10.1136/annrheumdis-2022-222155.
11.	Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut, 2019, 68(Suppl 3): s1-s106.
12.	Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. J Crohns Colitis, 2020, 14(1): 4-22.
13.	Ooi CJ, Hilmi I, Banerjee R, et al. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. J Gastroenterol Hepatol, 2019, 34(8): 1296-1315.
14.	中国炎症性肠病诊疗质控评估中心, 中华医学会消化病学分会炎症性肠病学组. 生物制剂治疗炎症性肠病专家建议意见. 中华炎性肠病杂志, 2021, 5(3): 193-206.
15.	U. S. Food & Drug Administration. Clinical pharmacology biopharmaceutics review(s) for Amjevita (adalimumab-atto). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024Orig1s000ClinPharmR.pdf.
16.	朱瑞芳, 李香莲, 丁肖梁, 等. 强直性脊柱炎患者血清阿达木单抗药物稳态谷浓度测定及变异研究. 中国药学杂志, 2019, 54(13): 1086-1091.
17.	Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA, 2011, 305(14): 1460-1468.
18.	Ding X, Zhu R, Wu J, et al. Early adalimumab and anti-adalimumab antibody levels for prediction of primary nonresponse in ankylosing spondylitis patients. Clin Transl Sci, 2020, 13(3): 547-554.
19.	Wynne C, Altendorfer M, Sonderegger I, et al. Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects. Expert Opin Investig Drugs, 2016, 25(12): 1361-1370.
20.	Kaur P, Chow V, Zhang N, et al. A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab. Ann Rheum Dis, 2017, 76(3): 526-533.
21.	Puri A, Niewiarowski A, Arai Y, et al. Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab/Humira, in healthy subjects. Br J Clin Pharmacol, 2017, 83(7): 1405-1415.
22.	Shin D, Lee Y, Kim H, et al. A randomized phase I comparative pharmacokinetic study comparing SB5 with reference adalimumab in healthy volunteers. J Clin Pharm Ther, 2017, 42(6): 672-678.
23.	Cao G, Yu J, Wu J, et al. A Randomized, double-blind, parallel-group, phase 1 clinical trial comparing the pharmacokinetic, safety, and immunogenicity of the biosimilar HS016 and the originator adalimumab in Chinese healthy male subjects. Clin Pharmacol Drug Dev, 2021, 10(3): 317-325.
24.	Zhang H, Wu M, Sun J, et al. Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: results of a randomized, double-blind, parallel-controlled, phase 1 study. Pharmacol Res Perspect, 2021, 9(2): e00733.
25.	Wang Y, Gao Z, Liu Z, et al. A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers. Expert Opin Biol Ther, 2022, 22(2): 225-234.
26.	国家药品监督管理局药品审批中心. 阿达木单抗注射液(JXSS1800013-14)申请上市技术审评报告. Available at: https://www.cde.org.cn/main/xxgk/postmarketpage?acceptidCODE=34953e55364c33d5662eb005970144cb.
27.	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, 4(5): 341-353.
28.	Nakase H, Motoya S, Matsumoto T, et al. Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial. Aliment Pharmacol Ther, 2017, 46(9): 873-882.
29.	Ungar B, Levy I, Yavne Y, et al. Optimizing anti-TNF-α therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol, 2016, 14(4): 550-557.
30.	Pouw MF, Krieckaert CL, Nurmohamed MT, et al. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis, 2015, 74(3): 513-518.
31.	Jani M, Chinoy H, Warren RB, et al. Clinical utility of random anti-tumor necrosis factor drug-level testing and measurement of antidrug antibodies on the long-term treatment response in rheumatoid arthritis. Arthritis Rheumatol, 2015, 67(8): 2011-2019.
32.	Vogelzang EH, Kneepkens EL, Nurmohamed MT, et al. Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up. Ann Rheum Dis, 2014, 73(12): 2178-2182.
33.	Wilkinson N, Tsakok T, Dand N, et al. Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study. J Invest Dermatol, 2019, 139(1): 115-123.
34.	Menting SP, Coussens E, Pouw MF, et al. Developing a therapeutic range of adalimumab serum concentrations in management of psoriasis: a step toward personalized treatment. JAMA Dermatol, 2015, 151(6): 616-622.
35.	Han ZM, Elodie WH, Yan LH, et al. Correlation between ultrasonographic response and anti-tumor necrosis factor drug levels in Crohn's disease. Ther Drug Monit, 2022, 44(5): 659-664.
36.	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, 109(8): 1250-1256.
37.	Roblin X, Genin C, Nancey S, et al. Swapping versus dose optimization in patients losing response to adalimumab with adequate drug levels. Inflamm Bowel Dis, 2022, 28(5): 720-727.
38.	Ulijn E, den Broeder N, Wientjes M, et al. Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD. Ann Rheum Dis, 2020, 79(7): 867-873.
39.	Wientjes MHM, Atiqi S, Wolbink GJ, et al. Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial. Trials, 2021, 22(1): 406.
40.	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, 157(4): 985-996.
41.	Yao J, Jiang X, You JHS. Proactive therapeutic drug monitoring of adalimumab for pediatric Crohn's disease patients: a cost-effectiveness analysis. J Gastroenterol Hepatol, 2021, 36(9): 2397-2407.
42.	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, 13(8): 976-981.
43.	D'Haens GR, Sandborn WJ, Loftus EV, et al. Higher vs standard adalimumab induction dosing regimens and two maintenance strategies: randomized SERENE CD trial results. Gastroenterology, 2022, 162(7): 1876-1890.
44.	l'Ami MJ, Krieckaert CL, Nurmohamed MT, et al. Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial. Ann Rheum Dis, 2018, 77(4): 484-487.
45.	Chen DY, Chen YM, Hsieh TY, et al. Drug trough levels predict therapeutic responses to dose reduction of adalimumab for rheumatoid arthritis patients during 24 weeks of follow-up. Rheumatology (Oxford), 2016, 55(1): 143-148.

1. U. S. Food & Drug Administration. Label for HUMIRA^® (adalimumab) injection. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125057s417lbl.pdf.
2. Papamichael K, Afif W, Drobne D, et al. Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives. Lancet Gastroenterol Hepatol, 2022, 7(2): 171-185.
3. Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology, 2017, 153(3): 827-834.
4. Mitrev N, Vande CN, 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.
5. Cheifetz AS, Abreu MT, Afif W, et al. A comprehensive literature review and expert consensus statement on therapeutic drug monitoring of biologics in inflammatory bowel disease. Am J Gastroenterol, 2021, 116(10): 2014-2025.
6. Irving PM, Gecse KB. Optimizing therapies using therapeutic drug monitoring: current strategies and future perspectives. Gastroenterology, 2022, 162(5): 1512-1524.
7. Khan A, Berahmana AB, Day AS, et al. New Zealand Society of Gastroenterology Guidelines on therapeutic drug Monitoring in inflammatory bowel disease. N Z Med J, 2019, 132(1491): 46-62.
8. Melmed GY, Irving PM, Jones J, et al. Appropriateness of testing for anti-tumor necrosis factor agent and antibody concentrations, and interpretation of results. Clin Gastroenterol Hepatol, 2016, 14(9): 1302-1309.
9. 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, 17(9): 1655-1668.
10. Krieckaert CL, van Tubergen A, Gehin JE, et al. EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Ann Rheum Dis, 2022. DOI: 10.1136/annrheumdis-2022-222155.
11. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut, 2019, 68(Suppl 3): s1-s106.
12. Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. J Crohns Colitis, 2020, 14(1): 4-22.
13. Ooi CJ, Hilmi I, Banerjee R, et al. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. J Gastroenterol Hepatol, 2019, 34(8): 1296-1315.
14. 中国炎症性肠病诊疗质控评估中心, 中华医学会消化病学分会炎症性肠病学组. 生物制剂治疗炎症性肠病专家建议意见. 中华炎性肠病杂志, 2021, 5(3): 193-206.
15. U. S. Food & Drug Administration. Clinical pharmacology biopharmaceutics review(s) for Amjevita (adalimumab-atto). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024Orig1s000ClinPharmR.pdf.
16. 朱瑞芳, 李香莲, 丁肖梁, 等. 强直性脊柱炎患者血清阿达木单抗药物稳态谷浓度测定及变异研究. 中国药学杂志, 2019, 54(13): 1086-1091.
17. Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA, 2011, 305(14): 1460-1468.
18. Ding X, Zhu R, Wu J, et al. Early adalimumab and anti-adalimumab antibody levels for prediction of primary nonresponse in ankylosing spondylitis patients. Clin Transl Sci, 2020, 13(3): 547-554.
19. Wynne C, Altendorfer M, Sonderegger I, et al. Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects. Expert Opin Investig Drugs, 2016, 25(12): 1361-1370.
20. Kaur P, Chow V, Zhang N, et al. A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab. Ann Rheum Dis, 2017, 76(3): 526-533.
21. Puri A, Niewiarowski A, Arai Y, et al. Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab/Humira, in healthy subjects. Br J Clin Pharmacol, 2017, 83(7): 1405-1415.
22. Shin D, Lee Y, Kim H, et al. A randomized phase I comparative pharmacokinetic study comparing SB5 with reference adalimumab in healthy volunteers. J Clin Pharm Ther, 2017, 42(6): 672-678.
23. Cao G, Yu J, Wu J, et al. A Randomized, double-blind, parallel-group, phase 1 clinical trial comparing the pharmacokinetic, safety, and immunogenicity of the biosimilar HS016 and the originator adalimumab in Chinese healthy male subjects. Clin Pharmacol Drug Dev, 2021, 10(3): 317-325.
24. Zhang H, Wu M, Sun J, et al. Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: results of a randomized, double-blind, parallel-controlled, phase 1 study. Pharmacol Res Perspect, 2021, 9(2): e00733.
25. Wang Y, Gao Z, Liu Z, et al. A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers. Expert Opin Biol Ther, 2022, 22(2): 225-234.
26. 国家药品监督管理局药品审批中心. 阿达木单抗注射液(JXSS1800013-14)申请上市技术审评报告. Available at: https://www.cde.org.cn/main/xxgk/postmarketpage?acceptidCODE=34953e55364c33d5662eb005970144cb.
27. 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, 4(5): 341-353.
28. Nakase H, Motoya S, Matsumoto T, et al. Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial. Aliment Pharmacol Ther, 2017, 46(9): 873-882.
29. Ungar B, Levy I, Yavne Y, et al. Optimizing anti-TNF-α therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol, 2016, 14(4): 550-557.
30. Pouw MF, Krieckaert CL, Nurmohamed MT, et al. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis, 2015, 74(3): 513-518.
31. Jani M, Chinoy H, Warren RB, et al. Clinical utility of random anti-tumor necrosis factor drug-level testing and measurement of antidrug antibodies on the long-term treatment response in rheumatoid arthritis. Arthritis Rheumatol, 2015, 67(8): 2011-2019.
32. Vogelzang EH, Kneepkens EL, Nurmohamed MT, et al. Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up. Ann Rheum Dis, 2014, 73(12): 2178-2182.
33. Wilkinson N, Tsakok T, Dand N, et al. Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study. J Invest Dermatol, 2019, 139(1): 115-123.
34. Menting SP, Coussens E, Pouw MF, et al. Developing a therapeutic range of adalimumab serum concentrations in management of psoriasis: a step toward personalized treatment. JAMA Dermatol, 2015, 151(6): 616-622.
35. Han ZM, Elodie WH, Yan LH, et al. Correlation between ultrasonographic response and anti-tumor necrosis factor drug levels in Crohn's disease. Ther Drug Monit, 2022, 44(5): 659-664.
36. 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, 109(8): 1250-1256.
37. Roblin X, Genin C, Nancey S, et al. Swapping versus dose optimization in patients losing response to adalimumab with adequate drug levels. Inflamm Bowel Dis, 2022, 28(5): 720-727.
38. Ulijn E, den Broeder N, Wientjes M, et al. Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD. Ann Rheum Dis, 2020, 79(7): 867-873.
39. Wientjes MHM, Atiqi S, Wolbink GJ, et al. Using adalimumab serum concentration to choose a subsequent biological DMARD in rheumatoid arthritis patients failing adalimumab treatment (ADDORA-switch): study protocol for a fully blinded randomised superiority test-treatment trial. Trials, 2021, 22(1): 406.
40. 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, 157(4): 985-996.
41. Yao J, Jiang X, You JHS. Proactive therapeutic drug monitoring of adalimumab for pediatric Crohn's disease patients: a cost-effectiveness analysis. J Gastroenterol Hepatol, 2021, 36(9): 2397-2407.
42. 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, 13(8): 976-981.
43. D'Haens GR, Sandborn WJ, Loftus EV, et al. Higher vs standard adalimumab induction dosing regimens and two maintenance strategies: randomized SERENE CD trial results. Gastroenterology, 2022, 162(7): 1876-1890.
44. l'Ami MJ, Krieckaert CL, Nurmohamed MT, et al. Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial. Ann Rheum Dis, 2018, 77(4): 484-487.
45. Chen DY, Chen YM, Hsieh TY, et al. Drug trough levels predict therapeutic responses to dose reduction of adalimumab for rheumatoid arthritis patients during 24 weeks of follow-up. Rheumatology (Oxford), 2016, 55(1): 143-148.

Chinese Journal of Evidence-Based Medicine

Optimizing adalimumab therapies using therapeutic drug monitoring: current evidence and future perspectives

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