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FRI0188 IL-6 inhibitor or TNF inhibitor? A scoring method to predicts preferable treatment for rheumatoid arthritis
  1. J. Nakagawa1,
  2. Y. Koyama2,
  3. T. Horiuchi3,
  4. A. Uchino1,
  5. T. Ota1,
  6. S. Nagano1
  1. 1Center for Rheumatic Disease, Iizuka Hospital, Iizuka-shi
  2. 2Division of Rheumatology, Okayama Red Cross General Hospital, Okayama-shi
  3. 3Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka-shi, Japan

Abstract

Background TNF inhibitors are recommended as the first line biologics to date because of a great deal of evidence, however, some patients show more obvious response to IL-6 inhibitor (tocilizumab; TCZ) treatment. For the purpose of achieving early remission and efficient medical economics, it would be desirable to be able to predict the efficacy of each anti-cytokine therapy before treatment.

Objectives The purpose of this study is to establish a scoring method that predicts preferable treatment before starting either TCZ or TNF inhibitor.

Methods First, mRNA levels of IL-6 and TNF-α in the peripheral blood of 45 newly diagnosed RA patients were analyzed by using Agilent whole human genome 60K cDNA arrays. The correlation analysis between mRNA levels of IL-6 and TNF-α and the correlation analysis between each laboratory datum and the difference between IL-6 and TNF-α mRNA levels were performed.

Next, 183 patients given anti-cytokine therapy in our hospital were retrospectively analyzed. They were divided into 2 groups, Group A consisted of 37 patients treated with TCZ, and Group B consisted of 146 patients treated with TNF inhibitor. The correlation analysis between the labo-data at baseline and the ratio of the DAS28-ESR before and 6 months after treatment (DAS ratio) was performed for each group. Labo-data with a significant correlation to the DAS ratio were selected, and a scoring formula for predicting the efficacy of TCZ treatment was devised by using those labo-data. On the basis of this formula, a scoring table was devised. The propriety of this scoring system was investigated by the clinical data of 183 RA patients.

Results The correlation analysis between mRNA levels of IL-6 and TNF-α showed a significant inverse correlation between them. In order to find the useful laboratory datum to represent the balance between IL-6 and TNF-α, the correlation analysis was performed between each laboratory datum and the difference between IL-6 and TNF-α mRNA levels. It showed that hemoglobin (Hb), platelet count (Plt), ALT, and ESR have significant correlation to the difference of IL-6 and TNF-α level. AST also have weak correlation to it.

Next, the correlation analysis between DAS ratio and each labo-data in Group A showed that Hb, Plt, AST and ALT had significant correlation to the DAS ratio, whereas no similar correlation was shown in the Group B. On the basis of these results, the following scoring formula was devised:

Score = {120 × Plt1.4 × Hb(–1.9) × AST(–0.65) × ALT(–0.65)}2,

Then, on the basis of above formula, a scoring table was devised. Each item (Plt, Hb, AST, and ALT) has 0-10 points, and the full score is 40 points. When the scores calculated by this table were more than 20 points, response rates of Group A vs Group B were as follows; good resonse 60% vs 0%, more than moderate response 100% vs 66.7%, No response 0% vs 33.3%.

Conclusions The finding of inverse correlation between mRNA expression of IL-6 and of TNF-α in RA supports a possibility to establish a scoring method to predict dominant cytokine that should be targeted for the treatment. As our scoring system was devised from retrospective analysis, it requires accumulation of data for the better accuracy. However this kind of approach would help to guide the selection of either the TNF inhibitor or the IL-6 inhibitor for each RA patient.

Disclosure of Interest None Declared

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