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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, Jin1
  • Koyama, Yoshinobu2
  • Kawakami, Atsushi3
  • Ueki, Yukitaka4
  • Tsukamoto, Hiroshi5
  • Horiuchi, Takahiko6
  • Nagano, Shuji7
  • Uchino, Ayumi7
  • Ota, Toshiyuki7
  • Akahoshi, Mitsuteru1
  • Akashi, Koichi1
  • 1 Kyushu University Graduate School of Medical Sciences, Department of Medicine and Biosystemic Science, Fukuoka, 812-8582, Japan , Fukuoka (Japan)
  • 2 Division of Rheumatology, Japanese Red-Cross Okayama Hospital, Center for Autoimmune Diseases, 2-1-1 Aoe, Kita-ku, Okayama, 700-8607, Japan , Kita-ku (Japan)
  • 3 Nagasaki University Graduate School of Biomedical Sciences, Department of Immunology and Rheumatology, Nagasaki, 852-8501, Japan , Nagasaki (Japan)
  • 4 Sasebo Chuo Hospital, Rheumatic and Collagen Disease Center, Sasebo, 857-1195, Japan , Sasebo (Japan)
  • 5 Shin-Kokura Hospital, Department of Rheumatology, Kitakyushu, 803-8505, Japan , Kitakyushu (Japan)
  • 6 Kyushu University Beppu Hospital, Department of Internal Medicine and Clinical Immunology, Beppu, 874-0838, Japan , Beppu (Japan)
  • 7 Iizuka Hospital, Center for Rheumatic Diseases, Iizuka, 820-8505, Japan , Iizuka (Japan)
Published Article
Arthritis Research & Therapy
Springer Science and Business Media LLC
Publication Date
Aug 11, 2017
DOI: 10.1186/s13075-017-1387-9
Springer Nature


BackgroundCurrently, 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.MethodsThe 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.ResultsThere 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.ConclusionsThe 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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