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When to Check Drug Levels & Why

Stephen J. Balevic, MD, PhD, RhMSUS  |  Issue: March 2024  |  

References

  1. 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. 2023 Jan;82(1):65–73.
  2. Durcan L, Clarke WA, Magder LS, Petri M. Hydroxychloroquine blood levels in systemic lupus erythematosus: Clarifying dosing controversies and improving adherence. J Rheumatol. 2015;42(11):2092–2097.
  3. Derijks LJ, Gilissen LP, Engels LG, et al. Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease. Ther Drug Monit. 2006 Feb;28(1):45–50.
  4. Balevic et al. Interpreting hydroxychloroquine blood levels for medication non-adherence: A pharmacokinetic study. Manuscript under review.
  5. Balevic SJ, Randell R, Weiner D, et al. Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial. Lupus Sci Med. 2022 Nov; 9(1): e000811.
  6. Morales A, Salguti S, Miao CL, Lewis JD. Relationship between 6-mercaptopurine dose and 6-thioguanine nucleotide levels in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2007 Apr;13(4):380–385.
  7. Balevic SJ, Weiner D, Clowse MEB, et al. Hydroxychloroquine PK and exposure-response in pregnancies with lupus: The importance of adherence for neonatal outcomes. Lupus Sci Med. 2022 Jan;9(1):e000602.
  8. Balevic SJ, Sagcal-Gironella ACP. Precision medicine: Towards individualized dosing in pediatric rheumatology. Rheum Dis Clin North Am. 2022 Feb;48(1):305–330.
  9. Syversen SW, Jorgensen KK, Goll GL, et al. Effect of therapeutic drug monitoring vs standard therapy during maintenance infliximab therapy on disease control in patients with immune-mediated inflammatory diseases: A randomized clinical trial. JAMA. 2021 Dec;326(23):2375–2384.
  10. Vincent FB, Morand EF, Murphy K, et al. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: A real issue, a clinical perspective. Ann Rheum Dis. 2013; 72(2):165–178.
  11. Costedoat-Chalumeau N, Galicier L, Aumaître O, et al. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013 Nov;72(11):1786–1792.
  12. Chen DY, Chen YM, Tsai WC, et al. Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis. Ann Rheum Dis. 2015 Mar;74(3):e16.
  13. Pouw MF, Krieckaert CL, Nurmohamed MT, et al. Key findings towards optimising adalimumab treatment: The concentrationeffect curve. Ann Rheum Dis. 2015;74(3): 513–518.
  14. Sanmarti R, Inciarte-Mundo J, Estrada-Alarcon P, et al. Towards optimal cut-off trough levels of adalimumab and etanercept for a good therapeutic response in rheumatoid arthritis. Results of the INMUNOREMAR study. Ann Rheum Dis. 2015 Aug;74(8):e42.
  15. Vande Casteele N, Herfarth H, Katz J, Falck-Ytter Y, Singh S. 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 e836.
  16. Daien CI, Daien V, Parussini E, et al. Etanercept concentration in patients with rheumatoid arthritis and its potential influence on treatment decisions: A pilot study. J Rheumatol. 2012 Aug;39(8):1533–1538.
  17. Frances C, Cosnes A, Duhaut P, et al. Low blood concentration of hydroxychloroquine in patients with refractory cutaneous lupus erythematosus: A French multicenter prospective study. Arch Dermatol. 2012 Apr; 148(4):479–484.
  18. Costedoat-Chalumeau N, Houssiau F, Izmirly P, et al. A prospective international study on adherence to treatment in 305 patients with flaring SLE: Assessment by drug levels and self-administered questionnaires. Clin Pharmacol Ther. 2019 Aug;106(2):374–382.
  19. Ting TV, Kudalkar D, Nelson S, et al. Usefulness of cellular text messaging for improving adherence among adolescents and young adults with systemic lupus erythematosus. J Rheumatol. 2012 Jan;39(1):174–179.
  20. Garg S, Unnithan R, Hansen KE, et al. Clinical significance of monitoring hydroxychloroquine levels in patients with systemic lupus erythematosus: A systematic review and metaanalysis. Arthritis Care Res (Hoboken). 2021 May;73(5):707–716.
  21. Zahr N, Urien S, Funck-Brentano C, et al. Evaluation of hydroxychloroquine blood concentrations and effects in childhood-onset systemic lupus erythematosus. Pharmaceuticals (Basel). 2021 Mar;14(3):273.
  22. Petri M, Elkhalifa M, Li J, et al. Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy. Arthritis Rheumatol. 2020 Mar;72(3):448–453.
  23. Neumann I, Fuhrmann H, Fang IF, et al. Association between mycophenolic acid 12-h trough levels and clinical endpoints in patients with autoimmune disease on mycophenolate mofetil. Nephrol Dial Transplant. 2008 Nov;23(11):3514–3520.
  24. Woillard JB, Bader-Meunier B, Salomon R, et al. Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring. Br J Clin Pharmacol. 2014 Oct;78(4):867–876.
  25. Lertdumrongluk P, Somparn P, Kittanamongkolchai W, et al. Pharmacokinetics of mycophenolic acid in severe lupus nephritis. Kidney Int. 2010 Aug;78(4):389–395.
  26. Zahr N, Arnaud L, Marquet P, et al. Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum. 2010 Jul;62(7):2047–2054.
  27. Godron-Dubrasquet A, Woillard JB, Decramer S, et al. Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis. Pediatr Nephrol. 2021 Jul;36(2):341–347.
  28. Chen Y, Sun L, Xu H, et al. PK/PD Study of mycophenolate mofetil in children with systemic lupus erythematosus to inform model-based precision dosing. Front Pharmacol. 2020 Dec;11:605060.
  29. Sagcal-Gironella AC, Fukuda T, Wiers K, et al. Pharmacokinetics and pharmacodynamics of mycophenolic acid and their relation to response to therapy of childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum. 2011 Feb;40(4):307–313.
  30. Askanase AD, Wallace DJ, Weisman MH, et al. Use of pharmacogenetics, enzymatic phenotyping, and metabolite monitoring to guide treatment with azathioprine in patients with systemic lupus erythematosus. J Rheumatol. 2009 Jan;36(1):89–95.

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