SAT0118 PRETREATMENT PREDICTION OF INDIVIDUAL OUTCOME OF RHEUMATOID ARTHRITIS PATIENTTO INFLIXIMAB THERAPY USING SERUM BIOMARKERS AND CLINICAL DATA
Authors: Kazuyuki Yoshizaki, Kazuko Uno, Tsutomu Takeuchi, Keisuke Izumi, Mitsuhiro Iwahashi, Hitoshi Fujimiya
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Infliximab (IFX), is a most effective b-DMRD, and results in a 60% remission rate on average in rheumatoid arthritis (RA) patients. The remaining 40% of patients undergo other biologics treatments that follow a 'treat-to-target method' until they achieve remission. Predicting in advance that a patient cannot achieve clinical remission with IFX, would allow doctors to start such patients on treat-to-target treatments sooner. Unfortunately, no reliable method has yet been found to predict patient-response. <h3>Objectives:</h3> We tried to establish a prediction method using the serum of individual patient with RA related biomarkers present in varying amounts before they underwent IFX. <h3>Methods:</h3> This study uses an observational retrospective study with 85 patients. 22 clinical data were used as explanation variables, such as, disease duration, combination of c-DMRDs, DAS 28-ESR, and day 0 laboratory data. 84 biomarkers in patients' pretreatment serum were measured using Multi-Plex Human Cytokine Chemokine beads array. DAS-28-ESR after 24 weeks was used as an objective variable. Patients administered IFX with regular method were divided into two groups: complete remission (DAS 28-ESR&lt;2.6) and non-remission (DAS 28-ESR2.6) at 24 weeks. The log–transformed value of all parameters were used for the statistical analysis. We used the least ?absolute shrinkage and selection operator (Lasso) approach to select combination markers that were most predictive of remission. In the process of multi-marker prognostic model building, to avoid over fitting, leave-one-out cross validation (LOOCV) was used to evaluate the performance of the multi-marker model. The receiver operating characteristic (ROC) analysis was used to evaluate the ability of the models to predict the 24-week outcome of patients. The area under the ROC curve is the product of the cross validation procedure. <h3>Results:</h3> We selected a combination from 104 markers. 3 to 5 combinations were most predictive of remission with 1.405 Cohen's d and at 0.85 AUC, 0.826 PPV, 0.882 NPV, and 0.689 ACC. On the contrary, using 22 clinical parameters, AUC, PPV, NPV and ACC were 0.726, 0.713, 0.649 and 0.673, respectively. <h3>Conclusion:</h3> Using the pre-treatment serum, we were able to predict with high accuracy patients who would achieve remission. Our method is stable and economical; therefore, it may be applicable as a way of identifying individual patients who are resistant to IFX therapy, so as to avoid treating them with IFX in the first place. The next step is to confirm these results in larger scale retrospective and prospective studies. The first highly accurate method identified for predicting remission and non-remission in individual RA patients who are targeted for IFX treatment. <h3>Reference</h3> [1] Uno K, Yoshizaki K, et all. Pretreatment Prediction of Individual Rheumatoid Arthritis Patients' Response to Anti-Cytokine Therapy Using Serum Cytokine/Chemokine/Soluble Receptor Biomarkers. PLoS One. 2015Jul15;10(7): e0132055. <h3>Acknowledgement:</h3> Russel Pandra for helping abstract translation <h3>Disclosure of Interests:</h3> Kazuyuki Yoshizaki: None declared, Kazuko Uno: None declared, Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Mitsuhiro Iwahashi: None declared, Hitoshi Fujimiya: None declared