Tocilizumab Dose Tapering Based on a Model-Based Algorithm is Feasible in Clinical Practice: A Short Communication
Tocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been...
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| Vydáno v: | Therapeutic drug monitoring Ročník 46; číslo 3; s. 410 |
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| Médium: | Journal Article |
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United States
01.06.2024
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| ISSN: | 1536-3694, 1536-3694 |
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| Abstract | Tocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been described. However, no clinical trials have been published to date on this subject. Therefore, the objective of this study was to assess the feasibility of the tapering of intravenous (iv) tocilizumab with the use of a pharmacokinetic model-based algorithm in RA patients.
A randomized controlled trial with a double-blind design and follow-up of 24 weeks was conducted. RA patients who received the standard of tocilizumab for at least the past 24 weeks, which is 8 mg/kg every 4 weeks, were included. Patients with a tocilizumab serum concentration above 5 mg/L at trough were randomized between concentration-guided dose tapering, referred to as therapeutic drug monitoring (TDM), or the standard 8 mg/kg dose. In the TDM group, the tocilizumab dose was tapered with a recently published model-based algorithm to achieve a target concentration of 4-6 mg/L after 20 weeks of dose tapering.
Twelve RA patients were included and 10 were randomized between the TDM and standard dose group. The study was feasible regarding the predefined feasibility criteria and patients had a positive attitude toward therapeutic drug monitoring. In the TDM group, the tocilizumab trough concentration within patients decreased on average by 24.5 ± 18.3 mg/L compared with a decrease of 2.8 ± 12 mg/L in the standard dose group. None of the patients in the TDM group reached the drug range of 4-6 mg/L. Instead, tocilizumab concentrations of 1.6 and 1.5 mg/L were found for the 2 patients who completed follow-up on the tapered dose. No differences in RA disease activity were observed between the 2 study groups.
This study was the first to show that it is feasible to apply a dose-reduction algorithm based on a pharmacokinetic model in clinical practice. However, the current algorithm needs to be optimized before it can be applied on a larger scale. |
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| AbstractList | Tocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been described. However, no clinical trials have been published to date on this subject. Therefore, the objective of this study was to assess the feasibility of the tapering of intravenous (iv) tocilizumab with the use of a pharmacokinetic model-based algorithm in RA patients.BACKGROUNDTocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been described. However, no clinical trials have been published to date on this subject. Therefore, the objective of this study was to assess the feasibility of the tapering of intravenous (iv) tocilizumab with the use of a pharmacokinetic model-based algorithm in RA patients.A randomized controlled trial with a double-blind design and follow-up of 24 weeks was conducted. RA patients who received the standard of tocilizumab for at least the past 24 weeks, which is 8 mg/kg every 4 weeks, were included. Patients with a tocilizumab serum concentration above 5 mg/L at trough were randomized between concentration-guided dose tapering, referred to as therapeutic drug monitoring (TDM), or the standard 8 mg/kg dose. In the TDM group, the tocilizumab dose was tapered with a recently published model-based algorithm to achieve a target concentration of 4-6 mg/L after 20 weeks of dose tapering.METHODSA randomized controlled trial with a double-blind design and follow-up of 24 weeks was conducted. RA patients who received the standard of tocilizumab for at least the past 24 weeks, which is 8 mg/kg every 4 weeks, were included. Patients with a tocilizumab serum concentration above 5 mg/L at trough were randomized between concentration-guided dose tapering, referred to as therapeutic drug monitoring (TDM), or the standard 8 mg/kg dose. In the TDM group, the tocilizumab dose was tapered with a recently published model-based algorithm to achieve a target concentration of 4-6 mg/L after 20 weeks of dose tapering.Twelve RA patients were included and 10 were randomized between the TDM and standard dose group. The study was feasible regarding the predefined feasibility criteria and patients had a positive attitude toward therapeutic drug monitoring. In the TDM group, the tocilizumab trough concentration within patients decreased on average by 24.5 ± 18.3 mg/L compared with a decrease of 2.8 ± 12 mg/L in the standard dose group. None of the patients in the TDM group reached the drug range of 4-6 mg/L. Instead, tocilizumab concentrations of 1.6 and 1.5 mg/L were found for the 2 patients who completed follow-up on the tapered dose. No differences in RA disease activity were observed between the 2 study groups.RESULTSTwelve RA patients were included and 10 were randomized between the TDM and standard dose group. The study was feasible regarding the predefined feasibility criteria and patients had a positive attitude toward therapeutic drug monitoring. In the TDM group, the tocilizumab trough concentration within patients decreased on average by 24.5 ± 18.3 mg/L compared with a decrease of 2.8 ± 12 mg/L in the standard dose group. None of the patients in the TDM group reached the drug range of 4-6 mg/L. Instead, tocilizumab concentrations of 1.6 and 1.5 mg/L were found for the 2 patients who completed follow-up on the tapered dose. No differences in RA disease activity were observed between the 2 study groups.This study was the first to show that it is feasible to apply a dose-reduction algorithm based on a pharmacokinetic model in clinical practice. However, the current algorithm needs to be optimized before it can be applied on a larger scale.CONCLUSIONSThis study was the first to show that it is feasible to apply a dose-reduction algorithm based on a pharmacokinetic model in clinical practice. However, the current algorithm needs to be optimized before it can be applied on a larger scale. Tocilizumab in the treatment of rheumatoid arthritis (RA) is a potential candidate for concentration-guided tapering because the standard dose of tocilizumab results in a wide range of serum concentrations, usually above the presumed therapeutic window, and an exposure-response relationship has been described. However, no clinical trials have been published to date on this subject. Therefore, the objective of this study was to assess the feasibility of the tapering of intravenous (iv) tocilizumab with the use of a pharmacokinetic model-based algorithm in RA patients. A randomized controlled trial with a double-blind design and follow-up of 24 weeks was conducted. RA patients who received the standard of tocilizumab for at least the past 24 weeks, which is 8 mg/kg every 4 weeks, were included. Patients with a tocilizumab serum concentration above 5 mg/L at trough were randomized between concentration-guided dose tapering, referred to as therapeutic drug monitoring (TDM), or the standard 8 mg/kg dose. In the TDM group, the tocilizumab dose was tapered with a recently published model-based algorithm to achieve a target concentration of 4-6 mg/L after 20 weeks of dose tapering. Twelve RA patients were included and 10 were randomized between the TDM and standard dose group. The study was feasible regarding the predefined feasibility criteria and patients had a positive attitude toward therapeutic drug monitoring. In the TDM group, the tocilizumab trough concentration within patients decreased on average by 24.5 ± 18.3 mg/L compared with a decrease of 2.8 ± 12 mg/L in the standard dose group. None of the patients in the TDM group reached the drug range of 4-6 mg/L. Instead, tocilizumab concentrations of 1.6 and 1.5 mg/L were found for the 2 patients who completed follow-up on the tapered dose. No differences in RA disease activity were observed between the 2 study groups. This study was the first to show that it is feasible to apply a dose-reduction algorithm based on a pharmacokinetic model in clinical practice. However, the current algorithm needs to be optimized before it can be applied on a larger scale. |
| Author | van den Berg, Stefan P H Huitema, Alwin D R Boekel, Laura Leeuw, Maureen Rispens, Theo Layegh, Zohra Elkayam, Ori Pel, Sara de Vries, Annick Ruwaard, Jill Bastida, Carla Wolbink, Gertjan Dorlo, Thomas P C Hooijberg, Femke Nurmohamed, Mike |
| Author_xml | – sequence: 1 givenname: Femke surname: Hooijberg fullname: Hooijberg, Femke organization: Department of Rheumatology, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands – sequence: 2 givenname: Zohra surname: Layegh fullname: Layegh, Zohra organization: Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 3 givenname: Maureen surname: Leeuw fullname: Leeuw, Maureen organization: Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam, the Netherlands – sequence: 4 givenname: Laura surname: Boekel fullname: Boekel, Laura organization: Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam, the Netherlands – sequence: 5 givenname: Stefan P H surname: van den Berg fullname: van den Berg, Stefan P H organization: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands – sequence: 6 givenname: Jill surname: Ruwaard fullname: Ruwaard, Jill organization: Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam, the Netherlands – sequence: 7 givenname: Carla surname: Bastida fullname: Bastida, Carla organization: Department of Pharmacy, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain – sequence: 8 givenname: Alwin D R surname: Huitema fullname: Huitema, Alwin D R organization: Department of Pharmacology, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 9 givenname: Sara surname: Pel fullname: Pel, Sara organization: Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel; and – sequence: 10 givenname: Ori surname: Elkayam fullname: Elkayam, Ori organization: Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel; and – sequence: 11 givenname: Annick surname: de Vries fullname: de Vries, Annick organization: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands – sequence: 12 givenname: Mike surname: Nurmohamed fullname: Nurmohamed, Mike organization: Department of Rheumatology, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands – sequence: 13 givenname: Theo surname: Rispens fullname: Rispens, Theo organization: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands – sequence: 14 givenname: Thomas P C surname: Dorlo fullname: Dorlo, Thomas P C organization: Department of Pharmacy, Uppsala University, Uppsala, Sweden – sequence: 15 givenname: Gertjan surname: Wolbink fullname: Wolbink, Gertjan organization: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, Amsterdam, the Netherlands |
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| SubjectTerms | Adult Aged Algorithms Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - pharmacokinetics Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - administration & dosage Antirheumatic Agents - blood Antirheumatic Agents - pharmacokinetics Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - drug therapy Dose-Response Relationship, Drug Double-Blind Method Drug Monitoring - methods Drug Tapering - methods Feasibility Studies Female Humans Male Middle Aged |
| Title | Tocilizumab Dose Tapering Based on a Model-Based Algorithm is Feasible in Clinical Practice: A Short Communication |
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