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＜博士論文＞
一般臨床検査値によるRAに対するTNF阻害及びIL-6阻害の有効性予測スコア : 多施設後方視的観察研究
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| 概要 | BACKGROUND:Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individua...l 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.続きを見る |
本文ファイル
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med3101_abstract
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169 KB | 318 | 要旨 | |
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med3101_summary
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169 KB | 518 | 要約 | |
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med3101_review
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168 KB | 255 | 審査結果要旨 |
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| 登録日 | 2018.05.30 |
| 更新日 | 2018.08.31 |