A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis: a retrospective, multicenter observational study

Jin Nakagawa, Yoshinobu Koyama, Atsushi Kawakami, Yukitaka Ueki, Hiroshi Tsukamoto, Takahiko Horiuchi, Shuji Nagano, Ayumi Uchino, Toshiyuki Ota, Mitsuteru Akahoshi, Koichi Akashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i.

METHODS: The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients.

RESULTS: There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively.

CONCLUSIONS: The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.

Original languageEnglish
Number of pages1
JournalArthritis research & therapy
Volume19
Issue number1
DOIs
Publication statusPublished - Aug 11 2017

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Multicenter Studies
Observational Studies
Interleukin-6
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Therapeutics
ROC Curve
Messenger RNA
Antirheumatic Agents
tocilizumab
Validation Studies
Disease Management
Aspartate Aminotransferases
Oligonucleotide Array Sequence Analysis
Alanine Transaminase
Platelet Count
Hemoglobins
Cytokines

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis : a retrospective, multicenter observational study. / Nakagawa, Jin; Koyama, Yoshinobu; Kawakami, Atsushi; Ueki, Yukitaka; Tsukamoto, Hiroshi; Horiuchi, Takahiko; Nagano, Shuji; Uchino, Ayumi; Ota, Toshiyuki; Akahoshi, Mitsuteru; Akashi, Koichi.

In: Arthritis research & therapy, Vol. 19, No. 1, 11.08.2017.

Research output: Contribution to journalArticle

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T1 - A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis

T2 - a retrospective, multicenter observational study

AU - Nakagawa, Jin

AU - Koyama, Yoshinobu

AU - Kawakami, Atsushi

AU - Ueki, Yukitaka

AU - Tsukamoto, Hiroshi

AU - Horiuchi, Takahiko

AU - Nagano, Shuji

AU - Uchino, Ayumi

AU - Ota, Toshiyuki

AU - Akahoshi, Mitsuteru

AU - Akashi, Koichi

PY - 2017/8/11

Y1 - 2017/8/11

N2 - BACKGROUND: Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i.METHODS: The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients.RESULTS: There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively.CONCLUSIONS: The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.

AB - BACKGROUND: Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i.METHODS: The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients.RESULTS: There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively.CONCLUSIONS: The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.

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