Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy

Abstract

Objective: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T).

Methods: In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS) <smallest detectable change (SDC) at week 72.

Results: Of 318 patients enrolled, 271 completed the follow-up for 72 weeks and were subjects of the analyses. Factors [odds ratio (95% confidence interval)] significantly associated with the HAQ-DI ≤0.5 were SDAI remission at week 24 [2.99 (1.42–6.28), p = 0.004], baseline HAQ-DI [0.28 (0.18–0.45), p = 1.3 × 10⁻⁷], and baseline vdH-mTSS [0.986 (0.976–0.996), p = 0.009]. A factor associated with ΔvdH-mTSS < SDC was SDAI remission at week 24 [3.53 (1.62–7.71), p = 0.002].

Conclusion: Predictive validity of SDAI remission for good outcomes was verified in a T2T-implementing cohort in the current clinical settings.

Keywords:

• Health assessment questionnaire
• Modified Sharp score
• Rheumatoid arthritis
• Simplified disease activity index
• Treat-to-target

Acknowledgments

We thank the site investigators of the T2T Epidemiological Study Group who contributed in recruiting patients and collecting clinical data: Takahiko Sugihara (Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan), Yoshinori Nonomura (Department of Rheumatology, Tokyo Kyosai Hospital, Tokyo, Japan), Masayuki Inoo (Department of Rheumatology, Utazu-Hama Clinic, Kagawa, Japan), Makoto Soejima (Ome Municipal General Hospital, Ome, Japan), Hiroyuki Hagiyama (Department of Rheumatology, Yokohama City Minato Red Cross Hospital, Yokohama, Japan), Toshihiko Hidaka (Institute of Rheumatology, Zenjinkai Shimin-no-Mori Hospital, Miyazaki, Japan), Mitsuhiro Iwahashi (Higashihiroshima Memorial Hospital, Hiroshima, Japan), Shinya Hirata (Department of Hematology, Rheumatology, and Infectious Disease, Kumamoto University Graduate School of Medicine, Kumamoto, Japan), and Shuji Ohta (Oasis Clinic, Hitachi, Japan). We also thank Ms. Marie Kokido for her contribution at the secretariat of this study. We sincerely thank all the rheumatologists and medical staff who took care of the patients enrolled in this study.

Conflict of interest

Fumio Hirano and Waka Yokoyama have nothing to declare. Tokyo Medical and Dental University (TMDU) received unrestricted research grants for Department of Pharmacovigilance from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, with which TMDU paid the salary of Hayato Yamazaki. Koichi Amano received grants from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc. and received consultant fees from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Pfizer Japan Inc. Atsushi Kawakami received grants from AbbVie GK, Eisai Co., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Company, Astellas Pharma Inc., ONO Pharmaceutical Co., Kissei Pharmaceutical Co., Boehringer Ingelheim Japan., AstraZeneca Co., Otsuka Pharmaceutical Co., Chugai Pharmaceutical Co., Santen Pharmaceutical Co., Daiichi Sankyo Co. and MSD Co., a consultant fee from Astellas Pharma Inc., and speaker’s fees from AbbVie GK, Takeda Pharmaceutical Company, ONO Pharmaceutical Co., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., MSD Co., Takeda Pharmaceutical Company and Pfizer Japan. Taichi Hayashi has nothing to declare. Naoto Tamura received grants from Astellas Pharma Inc., Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd. Shinsuke Yasuda received a grant from Bristol-Myers Squibb K.K. Hiroaki Dobashi has nothing to declare. Takao Fujii belongs to the department that is financially supported by four pharmaceutical companies (Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Bristol-Myers K.K., and Eisai Co., Ltd.). Takao Fujii also received honoraria (lecture fee) from Bristol-Myers K.K., Ono Pharmaceutical Co., Ltd. and Pfizer Japan Inc., and grant/research funding from AbbVie GK., Pfizer Japan Inc., Astellas Pharma Inc., Takeda Pharmaceutical Co., Santen Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd. Satoshi Ito received honoraria from AbbVie GK, Bristol-Myers Squibb K.K., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co. Ltd., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K. Yuko Kaneko has received lecture fees from AbbVie GK, Eisai Co., Ltd., Chugai Pharmaceutical Co., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Bristol-Myers K.K., Astellas Pharma Inc., Pfizer, Janssen, Santen Pharmaceutical Co., Ltd., Kyowa Hakko Kirin, and UCB Japan. Toshihiro Matsui and Yasuaki Okuda and Kazuyoshi Saito have nothing to declare. Fumihito Suzuki received an honorarium from Santen Pharmaceutical Co. Ltd. Ryusuke Yoshimi has received a Bristol-Myers K.K. RA Clinical Investigation Grant. TMDU received unrestricted research grants for Department of Pharmacovigilance from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, with which TMDU paid the salary of Ryoko Sakai. Ryoko Sakai has received a research grant from Bristol-Myers Squibb K.K. Ryuji Koike has nothing to declare. Hitoshi Kohsaka received research grants/support from Ajinomoto Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Japan Science and Technology Agency, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Santen Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., AbbVie Inc., Astellas Pharma Inc., Japan Blood Products Organization, Bristol-Myers Squibb, Eisai Co., Ltd., Pfizer Inc., Actelion Pharmaceuticals Japan Ltd., Daiichi Sankyo Co., Ltd., and received honoraria (lecture fee) from Ono Pharmaceuticals Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Mitsubishi Tanabe Pharma Co. Nobuyuki Miyasaka has nothing to declare. TMDU received unrestricted research grants for Department of Pharmacovigilance from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, with which TMDU paid the salary of Masayoshi Harigai.

This work was supported by a grant-in-aid from the Ministry of Health, Labour and Welfare, Japan, for the Study Group on the Standardization of Clinical Practice of Rheumatoid Arthritis in Japan, the Ministry of Health, Labour and Welfare of Japan (H23-meneki-shitei-016 and H26-meneki-shitei-021 to N.M. and M.H.).