2629 - Postmarketing Surveillance of Tocilizumab for Rheumatoid Arthritis In Japan – Full Analysis Report of 7,901 Patients

Wednesday, November 9, 2011: 11:30 AM
W196b (McCormick Place West)
Hisashi Yamanaka, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, Masayoshi Harigai, Tokyo Medical and Dental Univ, Tokyo, Japan, Shigeko Inokuma, Japanese Red Cross Medical Center, Tokyo, Japan, Naoki Ishiguro, Nagoya University, Graduate School & Faculty of Medicine, Nagoya, Aichi, Japan, Junnosuke Ryu, Nihon University School of Medicine, Tokyo, Japan, Syuji Takei, Kagoshima University, Kagoshima City, Japan, Tsutomu Takeuchi, Keio University School of Medicine, Tokyo, Japan, Yoshiya Tanaka, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan, Youko Sano, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan and Takao Koike, Sapporo Medical Center NTT EC, Sapporo, Japan
Presentation Number: 2629

Background/Purpose: A postmarketing surveillance (PMS) was performed for all patients with rheumatoid arthritis (RA) who were treated with tocilizumab (TCZ) in Japan to investigate the safety and effectiveness in the daily clinical setting.

Method: This full analysis report includes 7,901 patients. They received 8 mg/kg of TCZ every 4 weeks, and were observed for 28 weeks. Baseline characteristics, effectiveness as measured by 28-joint disease activity score (DAS28-ESR) and Boolean remission criteria (tender joint count ≤ 1, swollen joint count ≤ 1, patient global assessment [on 0–10 scale] ≤ 1, and serum concentration of C-reactive protein [mg/dL] ≤ 1), and all adverse events (AEs) were assessed.

Result: Baseline patient characteristics were as follows: mean age of 58.7 years (≥70 years of age in 20.7% of patients); mean disease duration of RA of 10.4 years (≥10 years in 37.8%); respiratory comorbidities in 17.0% and cardiac comorbidities in 5.1%; previous TNF inhibitor use in 62.8%; and concomitant methotrexate (MTX) use in 55.8% and concomitant glucocorticoid use in 74.0%. Mean baseline DAS28-ESR was 5.5, which declined to 2.9 at week 28 (LOCF method); 47.6% of patients achieved DAS28 remission (DAS28-ESR < 2.6), and 15.1% of patients achieved Boolean remission. The incidences of DAS28 remission and Boolean remission in patients with disease duration <2 years were significantly better than those in patients with ≥10 years' disease duration (p < 0.001, χ2 test). TNF inhibitor naïve patients showed significantly better response than the patients with prior anti-TNF use (p < 0.001, χ2 test)(Table).

The incidences of total and serious AEs (SAEs) were 43.9% and 9.6%, respectively. The incidence of SAEs was higher in the patients whose disease duration was ≥10 years (p < 0.001, χ2test, vs. <10 years) or who did not use MTX concomitantly (p < 0.001, χ2test, vs. concomitant MTX use) (Table). Infections and infestations were the most frequent AEs (11.1%) and the most frequent SAEs (3.8%). Although malignancies were reported as AEs in 39 patients (0.5%), no specific patterns were observed. Gastrointestinal disorders were reported in 373 patients (4.7%) including 13 (0.16%) gastrointestinal tract perforations. Thirty-five patients died within 28 weeks, and the standardized mortality ratio, with the Japanese general population in 2008 as a control, was 1.15 (95%CI: 0.83–1.61), which was numerically lower than the previous report (1.66; 95%CI: 1.12–2.46 from the interim analysis reports of 3,818 patients) and similar to the results reported in the Japanese cohort study of RA patients (Nakajima A, et al. Scand J Rheumatol. 2010; 39: 360–7)

Conclusion: The results from this study revealed that TCZ was effective and well-tolerated in Japanese RA patients in the daily clinical setting.

Incidence

total

Disease duration (years) 

Anti-TNF naïve

Anti-TNF used

<2

2≤ >10

10≤

MTX+

MTX-

MTX+

MTX-

DAS28

remission

47.6

56.1*

50.1

42.4

60.5†¶

50.6

45.6

39.1

Boolean

remission

15.1

22.3*

16.4

10.7

22.1

20.2

12.0

11.7

AEs

43.9

43.8

43.4

46.3

42.0

43.0

45.4

43.5

SAEs

9.6

8.5*

8.3

12.0

8.7

10.8

8.1

11.8

Infections

11.1

8.9*

9.4

14.0

10.0§

12.0

10.5

12.0

Serious

infections

3.8

2.6*

3.3

4.9

3.6

4.5

3.1

4.4

*;p<0.001 between <2years and ≤10 years, †;p<0.001, ‡;p<0.01, §;p<0.05 between

 MTX+ and MTX-, ¶;p<0.001 between anti-TNF naïve and anti-TNF used  


Keywords: Japanese, cytokines, rheumatoid arthritis (RA) and tocilizumab

Disclosure: H. Yamanaka, Abbott Japan, Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Co. Ltd., and Pfizer Japan Inc., 2, Abbott Japan, Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Co. Ltd., and Pfizer Japan Inc., 5, Abbott Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Co. Ltd., and Pfizer Japan Inc., 8 ; M. Harigai, Abbott Japan, Astellas, Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd,, 2, Abbott Japan, Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd, 5, Abbott Japan, Bristol-Myers Japan, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd, 8 ; S. Inokuma, None; N. Ishiguro, Abbott Japan, Chugai Pharmaceutical Co. Ltd., Daiichi-Sankyo Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 8, Abbott Japan, Chugai Pharmaceutical Co. Ltd., Daiichi-Sankyo Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 2 ; J. Ryu, None; S. Takei, None; T. Takeuchi, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Novartis, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 5, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Novartis, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 2, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Novartis, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 8 ; Y. Tanaka, Abbott Japan, Astellas Pharma, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Merck & Co. Inc, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 2, Abbott Japan, Astellas Pharma, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Merck & Co. Inc, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 5, Abbott Japan, Astellas Pharma, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Merck & Co. Inc, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 8 ; Y. Sano, Chugai Pharmaceutical, 3 ; T. Koike, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 2, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 5, Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd., 8 .