Effectiveness and Safety of Tocilizumab in Biologics-Naive RA Patients - Postmarketing Surveillance for Investigating Success in Achieving Clinical and Functional Remission and Sustaining Efficacy with Tocilizumab in Biologics-Naive RA Patients (FIRST Bio) Study

Naoki Ishiguro¹, Tatsuya Atsumi², Masayoshi Harigai³, Tsuneyo Mimori⁴, Norihiro Nishimoto⁵, Takayuki Sumida⁶, Tsutomu Takeuchi⁷, Yoshiya Tanaka⁸, Nobuhiro Takagi⁹, Ayako Nakasone¹⁰ and Hisashi Yamanaka¹¹, ¹Department of Orthopedic Suregery, Nagoya University Hospital, Nagoya, Japan, ²Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, ³Department of Phamacovigilance, Tokyo Medical and Dental University, Tokyo, Japan, ⁴Dept of Rheum & Clinical Immun, Kyoto Univ Grad Schl of Med, Kyoto, Japan, ⁵Osaka Rheumatology Clinic, Osaka, Japan, ⁶Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, ⁷Keio University School of Medicine, Tokyo, Japan, ⁸The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, ⁹Medical Science, Chugai Pharmaceutical, Tokyo, Japan, ¹⁰Chugai Pharmaceutical Co. Ltd, Tokyo, Japan, ¹¹Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: IL-6R signaling, methotrexate (MTX), rheumatoid arthritis (RA) and tocilizumab

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: The all-patient postmarketing surveillance (PMS) of tocilizumab (TCZ; PMS7901), which followed 7901 rheumatoid arthritis (RA) patients for 28 weeks (wks), showed that patients with high probability of remission and low probability of developing serious infections (SIs) were most likely to be those in early and less advanced stages of RA and who had not received biologics previously. The FIRST Bio study aimed to evaluate the overall effectiveness and safety of TCZ in biologics-naïve RA patients in the real clinical setting.

Methods: The FIRST Bio study was a 52-wk PMS. Patients who met the ACR/EULAR 2010 classification criteria and experienced inadequate response or were intolerant to ≥1 DMARDs received 8 mg/kg intravenous (IV) TCZ every 4 wks with or without DMARDs. Paired t-test was used for comparisons of continuous variables and X-squared test was used for categorical variables.

Results: Overall, 839 patients were observed. Patients from the FIRST Bio study had shorter mean disease duration (FIRST Bio, 7.5 years [y]; PMS7901, 10.4 y), and a higher percentage had less advanced Steinbrocker’s stage and class than those in PMS7901. At Wk 52, 72.3% of patients continued to receive IV TCZ (total, 718.4 patient-years [pty]). The mean Clinical disease activity index (CDAI) improved from baseline (23.3) to Wk 52 (6.6; p<0.0001). At Wk 52, CDAI remission rate was 36.8% and Boolean remission rate was 33.1%. Boolean remission rate was better in the FIRST Bio study at Wk 24 (27.7%) than in PMS7901 at Wk 28 (15.1%). The mean HAQ score improved from baseline (1.0) to Wk 52 (0.5; p<0.0001); in 65.1% patients, HAQ-DI score was ≤0.5 at Wk 52. While the CDAI remission rate was significantly higher in the <2-y vs ≥10-y disease duration categories at Wk 24 (p<0.0001), it increased in the ≥10-y group after Wk 24, making the difference not statistically significant at Wk 52 (Table). However, the remission rate in patients with HAQ score ≤0.5 was higher in the <2-y vs ≥10-y disease duration categories at Wk 24 and Wk 52. The incidence (events/100 pty) of total adverse events (AEs) and serious AEs (SAEs) was 75.7 and 18.1, respectively. Infections were the most frequent AEs (17.8) and SAEs (5.8). The incidence rates of SAEs and SIs were lower in FIRST Bio than in PMS7901 (PMS7901: SAEs, 27.4; SIs, 8.6). The mean dose of concomitant MTX decreased from baseline (9.1 mg/wk) to Wk 52 (6.4 mg/wk), and 19.3% patients discontinued MTX. The mean dose of concomitant glucocorticoid (GC) also decreased from baseline (5.4 mg/day) to Wk 52 (2.6 mg/day), and was suspended in 34.0% of patients. CDAI remission rate did not decrease in patients who discontinued MTX or GC.

Conclusion: The FIRST Bio study confirmed the high effectiveness and safety of TCZ in the real clinical setting in patients with less advanced RA who had not received biologics previously.

Table. Changes in CDAI and HAQ-DI remission rates over time in the FIRST Bio study
		Week 0	Week 12	Week 24	Week 36	Week 52
CDAI remission rate (%)	Total (n=722)	0.4	17.9	31.1	33.2	36.8
	<2 y (n=240)	0.8	21.6	40.2	40.4	42.9
	≥10 y (n=176)	0	12.6	20.5	27.3	33.5
HAQ-DIremission (≤0.5) rate (%)	Total (n=559)	34.3	59.8	62.0	64.9	65.1
	<2 y (n=183)	33.9	69.69	69.36	75.41	77.6
	≥10 y (n=140)	30.0	48.8	48.5	50.0	46.4

Disclosure: N. Ishiguro, AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi Tanabe, Pfizer and Takeda, 5,AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi Tanabe, Pfizer and Takeda, 8; T. Atsumi, Chugai, Eisai, Bristol-Myers Squibb, Astellas, Daiichi-Sankyo, Mitsubish-Tanabe, 2,Astellas, Mitsubish-Tanabe, 8; M. Harigai, AbbVie, Astellas, Chugai, Eisai, Mitsubishi Ono, Tanabe, Takeda and UCB, 2,Bristol-Myers Squibb, Chugai and Janssen, 5,AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Ono, Takeda, UCB and Pfizer, 8; T. Mimori, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, MSD, Nippon Kayaku, Nippon Shinyaku, Santen and Takeda, 2,Astellas, Bristol-Myers Squibb, Chugai, Mitsubishi Tanabe and Taisho Toyama, 8; N. Nishimoto, Chugai and Eisai, 2,Chugai, 3,Chugai, 5,Chugai, 7; T. Sumida, Chugai, 2,Chugai, 8; T. Takeuchi, AbbVie, Asahi Kasei, Asahi Kasei Medical, Astellas, Astra Zeneca, Bistol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Novartis, Pfizer, Santen, SymBio, Takeda, Taishyo Toyama and Teijin, 5,AbbVie, Asahi Kasei, Asahi Kasei Medical, Astellas, Astra Zeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Novartis, Pfizer, Santen, SymBio, Takeda, Taishyo Toyama and Teijin, 8; Y. Tanaka, Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, 8; N. Takagi, Chugai, 3; A. Nakasone, Chugai, 3; H. Yamanaka, Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, 5,AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Takeda, Teijin and UCB, 8.

To cite this abstract in AMA style:

Ishiguro N, Atsumi T, Harigai M, Mimori T, Nishimoto N, Sumida T, Takeuchi T, Tanaka Y, Takagi N, Nakasone A, Yamanaka H. Effectiveness and Safety of Tocilizumab in Biologics-Naive RA Patients – Postmarketing Surveillance for Investigating Success in Achieving Clinical and Functional Remission and Sustaining Efficacy with Tocilizumab in Biologics-Naive RA Patients (FIRST Bio) Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/effectiveness-and-safety-of-tocilizumab-in-biologics-naive-ra-patients-postmarketing-surveillance-for-investigating-success-in-achieving-clinical-and-functional-remission-and-sustaining-efficacy-wit/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effectiveness-and-safety-of-tocilizumab-in-biologics-naive-ra-patients-postmarketing-surveillance-for-investigating-success-in-achieving-clinical-and-functional-remission-and-sustaining-efficacy-wit/