FRI0099 PREDICTIVE FACTORS FOR REMISSION ACHIEVEMENT BY TOCILIZUMAB MONOTHERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER INADEQUATE RESPONSE TO METHOTREXATE: A POST HOC ANALYSIS OF THE SURPRISE STUDY
Authors: Masaru Kato, Yuko Kaneko, Yoshiya Tanaka, Masayuki Inoo, Hitomi Kobayashi-Haraoka, Koichi Amano, Masayuki Miyata, Yohko Murakawa, Hidekata Yasuoka, Shintaro Hirata, Hayato Nagasawa, Eiichi Tanaka, Nobuyuki Miyasaka, Hisashi Yamanaka, Kazuhiko Yamamoto, Isao Yokota, Tatsuya Atsumi, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Interleukin (IL)-6 pathway inhibitors are suggested by European League Against Rheumatism recommendations to have some advantages in rheumatoid arthritis (RA) patients who are not suitable to use methotrexate as comedication compared with other biological disease-modifying antirheumatic drugs. However, it remains to be elucidated what predicts remission achievement by IL-6 pathway inhibitor monotherapy. <h3>Objectives:</h3> To identify predictive factors for clinical and structural remission by tocilizumab without methotrexate in patients with RA. <h3>Methods:</h3> This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH) in active RA patients despite methotrexate therapy. The primary endpoint was the DAS28-ESR remission (&lt; 2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (ΔmTSS/year) was also assessed as an endpoint. The effect of clinical parameters, including serum levels of CRP, IL-6, serum amyloid A (SAA), MMP-3, RF and IgG at baseline, on the achievement of DAS28 remission at week 24 was estimated by logistic regression analysis. Multivariate analysis was performed after adjusting for age, gender, height, body weight, body mass index, disease duration, the dose of glucocorticoids, and that of methotrexate. <h3>Results:</h3> In SWITCH (n = 96), CRP, SAA, RF and DAS28 at baseline showed predictive value for DAS28 remission at week 24 in univariate analysis. Multivariate analysis confirmed SAA, RF and DAS28 at baseline, but not CRP, as predictive factors, with SAA having the highest value (OR [95%CI] by decrease of 5.0 μg/mL = 1.011 [1.002-1.020], p = 0.01, ROC-AUC = 0.731). SAA of &lt; 50.0 μg/mL showed extremely high predictive value for DAS28 remission (OR [95%CI] = 6.012 [1.997-18.096], p = 0.0008, ROC-AUC = 0.761). Furthermore, structural remission (ΔmTSS/year ≤ 0.5) rate at week 52 was significantly higher in patients with SAA of &lt; 50.0 μg/mL than those with SAA of ≥ 50.0 μg/mL (71% vs 51%, p = 0.048). In contrast, in ADD-ON (n = 98), only DAS28 at baseline showed predictive value for DAS28 remission at week 24 in both univariate and multivariate analysis. In patients with SAA &lt; 50.0 μg/mL, both DAS28 remission (75% vs 77%, p = 0.79) and structural remission (71% vs 68%, p = 0.71) rate were comparable between SWITCH and ADD-ON. <h3>Conclusion:</h3> SAA levels at baseline can predict the necessity of concomitant methotrexate in tocilizumab initiation in patients with RA. Patients with low levels of SAA at baseline may benefit similarly from tocilizumab therapy with and without methotrexate in terms of achieving clinical and structural remission. <h3>Reference:</h3> [1] Kaneko Y, et al. Ann Rheum Dis. 2016 Nov;75(11):1917-1923. Kaneko Y, et al. Ann Rheum Dis. 2018 Sep;77(9):1268-1275. <h3><b>Disclosure of Interests:</b> :</h3> Masaru Kato Grant/research support from: GSK, Actelion, Speakers bureau: GSK, Actelion, Bayer, Nippon Shinyaku, Eli Lilly, Chugai, Pfizer, Ayumi, Eisai, Asahi Kasei, Yuko Kaneko Grant/research support from: Abbvie, Eisai, Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, UCB, Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Masayuki Inoo: None declared, Hitomi Kobayashi-Haraoka: None declared, Koichi Amano Grant/research support from: Asahi Kasei Pharma, Chugai Pharmaceutical Co. Ltd., Speakers bureau: AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, Pfizer Japan Inc., Masayuki Miyata: None declared, Yohko Murakawa Grant/research support from: Asahi Kasei Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Teijin Pharma Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Paid instructor for: Kissei Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K. Eisai Co., Ltd., Speakers bureau: Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., UCB Japan Co. Ltd., Chugai Pharmaceutical Co., Ltd., AbbVie GK, Daiichi Sankyo Co., Ltd., AYUMI Pharmaceutical Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Company Limited, Sanofi K.K. Teijin Pharma Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Hidekata Yasuoka: None declared, Shintaro Hirata Grant/research support from: Eli Lilly, UCB, Consultant for: Bristol-Myers Squibb, Jansen, UCB, Paid instructor for: AbbVie, Eisai, Tanabe-Mitsubishi, Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, UCB, Hayato Nagasawa: None declared, Eiichi Tanaka Speakers bureau: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Nobuyuki Miyasaka: None declared, Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio, Kazuhiko Yamamoto Grant/research support from: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU., Speakers bureau: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU., Isao Yokota Speakers bureau: Chugai Pharma, Tatsuya Atsumi Grant/research support from: Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co., Ltd. and Pfizer Inc.. Alexion Inc., Bayer Yakuhin, Ltd,Otsuka Pharmaceutical Co., Ltd. Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Bristol-Myers Squibb Co., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Asahi Kasei Pharma Co., Consultant for: ONO PHARMACEUTICAL CO., LTD Sanofi K.K. Daiichi Sankyo Co., Ltd. Pfizer Inc., Speakers bureau: Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Pfizer Inc.,Daiichi Sankyo Co. Ltd., Bristol-Myers Squibb Co., Eli Lilly Japan K.K., 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.