IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis

Koji Takasugi, Keiichiro Nishida, Masamitsu Natsumeda, Misuzu Yamashita, Wataru Yamamoto, Kazuhiko Ezawa

Research output: Contribution to journalArticle

Abstract

Objective: We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3 mg/kg IFX. Methods: Among 42 patients allotted to receive 3 mg/kg IFX, 13 patients showed adequate response (DAS28 < 3.2) and 29 patients required dose escalation to 4.5 or 6 mg/kg after inadequate response (DAS28 ≥ 3.2) to 3 mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival. Results: One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0 pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16 pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712–1.006). In patients with IL-6 levels of less than 5.16 pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16 pg/mL and in those with levels greater than or equal to 5.16 pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p = .011). Conclusions: The results of our study indicated that a baseline serum level of IL-6 below 5.16 pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalModern Rheumatology
DOIs
Publication statusAccepted/In press - Aug 22 2017

Fingerprint

Interleukin-6
Rheumatoid Arthritis
Survival
Pharmaceutical Preparations
Serum
Infliximab
Interleukin-17
Biological Products
ROC Curve
Area Under Curve
Anti-Idiotypic Antibodies
Multivariate Analysis
Survival Rate
Sensitivity and Specificity

Keywords

  • anti-infliximab antibody
  • dose escalation
  • infliximab
  • interleukin (IL)-6
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis. / Takasugi, Koji; Nishida, Keiichiro; Natsumeda, Masamitsu; Yamashita, Misuzu; Yamamoto, Wataru; Ezawa, Kazuhiko.

In: Modern Rheumatology, 22.08.2017, p. 1-9.

Research output: Contribution to journalArticle

Takasugi, Koji ; Nishida, Keiichiro ; Natsumeda, Masamitsu ; Yamashita, Misuzu ; Yamamoto, Wataru ; Ezawa, Kazuhiko. / IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis. In: Modern Rheumatology. 2017 ; pp. 1-9.
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AU - Natsumeda, Masamitsu

AU - Yamashita, Misuzu

AU - Yamamoto, Wataru

AU - Ezawa, Kazuhiko

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N2 - Objective: We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3 mg/kg IFX. Methods: Among 42 patients allotted to receive 3 mg/kg IFX, 13 patients showed adequate response (DAS28 < 3.2) and 29 patients required dose escalation to 4.5 or 6 mg/kg after inadequate response (DAS28 ≥ 3.2) to 3 mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival. Results: One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0 pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16 pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712–1.006). In patients with IL-6 levels of less than 5.16 pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16 pg/mL and in those with levels greater than or equal to 5.16 pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p = .011). Conclusions: The results of our study indicated that a baseline serum level of IL-6 below 5.16 pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.

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