Skip to main content

Advertisement

SpringerLink
Log in

Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients: results of a 12-month observational prospective cohort study

  • Brief Report
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients’ status after ∼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58–161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1–5 μg/mL. One patient had very high ATI levels (>880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ATI:

Antibodies to infliximab

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

IFX:

Infliximab

INX:

Infliximab innovator

INB:

Infliximab biosimilar

IQR:

Interquartile range

TDM:

Therapeutic drug monitoring

TNFα:

Tumor necrosis factor alpha

References

  1. Krintel SB, Grunert VP, Hetland ML, Johansen JS, Rothfuss M, Palermo G et al (2013) The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure. Rheumatol Oxf Engl 52(7):1245–1253

    Article  CAS  Google Scholar 

  2. Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P et al (2013) A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 72(10):1605–1612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S et al (2013) A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 72(10):1613–1620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Park W, Lee SJ, Yun J, Yoo DH (2015) Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study. Expert Rev Clin Immunol 11(Suppl 1):S25–S31

    Article  PubMed  Google Scholar 

  5. Yoo DH, Racewicz A, Brzezicki J, Yatsyshyn R, Arteaga ET, Baranauskaite A et al (2015) A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther 18:82

    Article  Google Scholar 

  6. Park W, Yoo DH, Miranda P, Brzosko M, Wiland P, Gutierrez-Ureña S, et al. (2016) Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis 26

  7. Yoo DH, Prodanovic N, Jaworski J, Miranda P, Ramiterre E, Lanzon A, et al. (2016) Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis 29

  8. Gils A (2017) Combining therapeutic drug monitoring with biosimilars, a strategy to improve the efficacy of biologicals for treating inflammatory bowel diseases at an affordable cost. Dig Dis Basel Switz 35(1–2):61–68

    Article  Google Scholar 

  9. Schmitz EMH, van de Kerkhof D, Hamann D, van Dongen JLJ, Kuijper PHM, Brunsveld L, et al. (2015) Therapeutic drug monitoring of infliximab: performance evaluation of three commercial ELISA kits. Clin Chem Lab Med CCLM FESCC 20

  10. Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT et al (2006) Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum 54(3):711–715

    Article  PubMed  Google Scholar 

  11. Vande Casteele N, Gils A, Singh S, Ohrmund L, Hauenstein S, Rutgeerts P et al (2013) Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol 108(6):962–971

    Article  PubMed  Google Scholar 

  12. Ungar B, Chowers Y, Yavzori M, Picard O, Fudim E, Har-Noy O et al (2014) The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut 63(8):1258–1264

    Article  CAS  PubMed  Google Scholar 

  13. Wolbink GJ, Voskuyl AE, Lems WF, de Groot E, Nurmohamed MT, Tak PP et al (2005) Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis 64(5):704–707

    Article  CAS  PubMed  Google Scholar 

  14. Baraliakos X, Heldmann F, van den Bosch F, Burmester G, Gaston H, van der Horst-Bruinsma IE et al (2016) Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction. RMD Open 2(2):e000272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Plasencia C, Kneepkens EL, Wolbink G, Krieckaert CLM, Turk S, Navarro-Compán V et al (2015) Comparing tapering strategy to standard dosing regimen of tumor necrosis factor inhibitors in patients with spondyloarthritis in low disease activity. J Rheumatol 42(9):1638–1646

    Article  CAS  PubMed  Google Scholar 

  16. Pascual-Salcedo D, Plasencia C, Jurado T, Valle LG del, Sabina P, Diego C, et al. Dose-tapering of TNF inhibitors in daily rheumatology practice enables the maintenance of clinical efficacy while improving cost-effectiveness. J Pharmacovigil [Internet]. 2015 Aug 5 [cited 2017]; Available from: https://www.esciencecentral.org/journals/dosetapering-of-tnf-inhibitors-in-daily-rheumatology-practice-enables-the-maintenance-of-clinical-efficacy-while-improving-costeffectiveness-2329-6887-1000172.php?aid=58635

  17. Ghiti Moghadam M, Vonkeman HE, Ten Klooster PM, Tekstra J, van Schaardenburg D, Starmans-Kool M et al (2016) Stopping tumor necrosis factor inhibitor treatment in patients with established rheumatoid arthritis in remission or with stable low disease activity: a pragmatic multicenter, open-label randomized controlled trial. Arthritis Rheumatol Hoboken NJ 68(8):1810–1817

    Article  CAS  Google Scholar 

  18. Tanaka Y, Takeuchi T, Mimori T, Saito K, Nawata M, Kameda H et al (2010) Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis 69(7):1286–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. den Broeder AA, van Herwaarden N, van der Maas A, van den Hoogen FHJ, Bijlsma JW, van Vollenhoven RF et al (2013) Dose REduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non inferiority trial, the DRESS study. BMC Musculoskelet Disord 14:299

    Article  Google Scholar 

  20. Nikiphorou E, Kautiainen H, Hannonen P, Asikainen J, Kokko A, Rannio T, et al. (2015) Clinical effectiveness of CT-P13 (infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther 1–7

  21. Gentileschi S, Barreca C, Bellisai F, Biasi G, Brizi MG, Stefano RD et al (2016) Switch from infliximab to infliximab biosimilar: efficacy and safety in a cohort of patients with different rheumatic diseases. Expert Opin Biol Ther 16(10):1311–1312

    Article  PubMed  Google Scholar 

  22. Tweehuysen L, van den Bemt B.J.F., van Ingen I.L., de Jong A.J.L., van der Laan W.H., van den Hoogen F.H.J., den Broeder A.A. Clinical and immunogenicity outcomes after switching treatment from innovator infliximab to biosimilar infliximab in rheumatic diseases in daily clinical practice [Internet]. ACR Meeting Abstracts. [cited 2017 Feb 16] Available from: http://acrabstracts.org/abstract/clinical-and-immunogenicity-outcomes-after-switching-treatment-from-innovator-infliximab-to-biosimilar-infliximab-in-rheumatic-diseases-in-daily-clinical-practice/

  23. Benucci M, Gobbi FL, Bandinelli F, Damiani A, Infantino M, Grossi V et al (2016) Safety, efficacy and immunogenicity of switching from innovator to biosimilar infliximab in patients with spondyloarthritis: a 6-month real-life observational study. Immunol Res 23

Download references

Author information

Authors and Affiliations

  1. Clinical Laboratory, Máxima Medical Center, Veldhoven, the Netherlands

    E. M. H. Schmitz & M. A. C. Broeren

  2. Expert Center Clinical Chemistry, Eindhoven, the Netherlands

    E. M. H. Schmitz, V. Scharnhorst & M. A. C. Broeren

  3. Clinical Laboratory, Catharina Hospital, Eindhoven, the Netherlands

    E. M. H. Schmitz & V. Scharnhorst

  4. Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands

    E. M. H. Schmitz & V. Scharnhorst

  5. Department of Rheumatology, Máxima Medical Center, Eindhoven and Veldhoven, the Netherlands

    S. Benoy - De Keuster, A. J. L. Meier & R. A. M. Traksel

  6. Clinical Pharmacy, Máxima Medical Center, P.O. Box 7777, 5500 MB, Veldhoven, The Netherlands

    L. J. J. Derijks

Authors
  1. E. M. H. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Benoy - De Keuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. J. L. Meier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Scharnhorst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. A. M. Traksel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. A. C. Broeren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. J. J. Derijks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. J. J. Derijks.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmitz, E.M.H., Benoy - De Keuster, S., Meier, A.J.L. et al. Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients: results of a 12-month observational prospective cohort study. Clin Rheumatol 36, 2129–2134 (2017). https://doi.org/10.1007/s10067-017-3686-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-017-3686-6

Keywords

Search

Navigation