Malignancy Data in Tofacitinib-Treated Japanese Patients with Rheumatoid Arthritis

Yoshiya Tanaka¹, Tsutomu Takeuchi², Hisashi Yamanaka³, Naonobu Sugiyama M.D., Ph.D⁴, Takunari Yoshinaga⁴, Kanae Togo⁴, Jamie Geier⁵, Mary Boy⁵ and Carol Connell⁵, ¹The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, ²Keio University School of Medicine, Tokyo, Japan, ³Tokyo Women’s Medical University, Tokyo, Japan, ⁴Pfizer Japan Inc, Tokyo, Japan, ⁵Pfizer Inc, Groton, CT

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Cancer, Early Rheumatoid Arthritis, Malignancy, rheumatoid arthritis (RA) and tofacitinib

Session Information

Date: Sunday, November 8, 2015

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

Session Type: ACR Poster Session A

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

Background/Purpose: Tofacitinib
is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis
(RA). In the global tofacitinib RA clinical program, rates and types of
malignancies remained stable over time with increasing tofacitinib exposure;
the overall malignancy incidence rate (IR) (excluding non-melanoma skin cancer
[NMSC]) was 0.85 (95% CI, 0.70-1.02) events per 100 patient-years (pt-yrs);
age- and sex-adjusted standardized incidence ratio (SIR) vs. US SEER database was
1.17 (95% CI, 0.96-1.41).¹ This analysis evaluated malignancy (excluding
NMSC) in Japanese RA (JRA) pts in the tofacitinib clinical program, compared
with JRA and Japanese general populations (JGP).

Methods: Malignancy data were
pooled from 2 Phase (P) 2, 1 P3 and 1 open-label long-term extension (LTE) RA
studies conducted in Japan (April 2014 data cut). Pts received tofacitinib 5 or
10 mg twice daily (BID) in P3 and LTE; also 1, 3, and 15 mg BID in P2.

Malignancy data were also obtained for: JGP aged 16-<75
yrs (2010 data from the Cancer Information Service, National Cancer Center,
Japan)²; Japan Medical Data Center (JMDC) RA population aged 16-<75
yrs (Jan 2005 to Oct 2013).

Results:
556 JRA pts (1705 pt-yrs of exposure)
received tofacitinib in P2/P3/LTE studies; 22 pts had malignancies. From JMDC (23,481
pts in total), 14,728 pts received any treatment for RA; 2,317 pts received nonbiologic
or biologic DMARDs.

Cumulative
IRs for malignancy (excluding NMSC) in tofacitinib-treated JRA pts in clinical
trials are shown in the Figure; SIRs (95% CI) for malignancy (excluding NMSC) were
2.13 (1.33-3.22) vs. JGP, 1.21 (0.76-1.83) vs. JMDC population receiving any
treatment for RA, and 0.87 (0.55-1.32) vs. JMDC population receiving nonbiologic
or biologic DMARDs (Table).

Conclusion:
Following numerically lower incidence rates over months 0-12 with possible
effect of pre-randomization screening, the risk of all malignancies (excluding
NMSC) among JRA pts exposed to tofacitinib appears stable with increasing
exposure to tofacitinib. The overall malignancy rate in the tofacitinib-treated
JRA population was similar to the JMDC RA populations, and was increased
compared with the JGP. Given the limited pt-yrs accrued to date in Japan, ongoing
post-marketing surveillance will further evaluate malignancy among JRA pts
exposed to tofacitinib.

References:

1.
Curtis
et al. Ann Rheum Dis
doi:10.1136/annrheumdis-2014-205847.

2.
Cancer Information Service, National Cancer
Center, Japan http://ganjoho.jp/en/professional/statistics/table_download.html
(accessed Feb 24, 2015)

Table. Crude IR and SIR for malignancy (excluding NMSC) for tofacitinib-treated RA patients in Japanese clinical trials compared with reference populations
		Crude IR (95% CI), events/100 pt-yrs	SIR (95% CI)
Comparator population	Tofacitinib-treated RA patients in Japanese clinical trials	1.29 (0.81, 1.96)	–
Reference populations	JGP	0.55 (0.55, 0.55)	2.13 (1.33, 3.22)
	JMDC population receiving any treatment for RA	0.77 (0.68, 0.88)	1.21 (0.76, 1.83)
	JMDC population receiving nonbiologic or biologic DMARDs	1.09 (0.81, 1.42)	0.87 (0.55, 1.32)
CI, confidence intervals; IR, incidence rates; JGP, Japanese general population – 2010; JMDC, Japan Medical Data Center RA population – Jan 2005 to Oct 2013; NMSC, non-melanoma skin cancer; pt-yrs, patient-years; SEER, US National Cancer Institute Surveillance and Epidemiology and End Results database, 1992–2011; SIR, standardized incidence ratios.

Disclosure: Y. Tanaka, Pfizer, Mitsubishi-Tanabe Pharma Corporation, Abbott Japan, Eisai, Chugai Pharma, Janssen Pharma, Santen, Astellas Pharma, Daiichi-Sankyo, GlaxoSmithKline, Astra Zeneca, Actelion Pharma, Eli Lilly Japan, Nippon Kayaku, UCB Japan, Ono, and Novartis Pharma, 8,Pfizer, Mitsubishi-Tanabe Pharma Corporation, Abbott Japan, Eisai, Chugai Pharma, Janssen Pharma, Santen, Astellas Pharma, Daiichi-Sankyo, GlaxoSmithKline, Astra Zeneca, Actelion Pharma, Eli Lilly Japan, Nippon Kayaku, UCB Japan, Ono, and Novartis Pharma, 5; T. Takeuchi, Asahi Kasei Medical, Astra Zeneca, Bristol-Myers, Eli Lilly, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, and Novartis., 2,Asahi Kasei Medical, Astra Zeneca, Bristol-Myers, Eli Lilly, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, and Novartis., 9; H. Yamanaka, Pfizer, Chugai, Eisai, AbbVie, Takeda, Mitsubishi-Tanabe, Janssen, Bristol-Meyers, Saiichi-Sankyo, Astra Zeneca, 5,Pfizer, Chugai, Eisai, AbbVie, Takeda, Mitsubishi-Tanabe, Janssen, Bristol-Meyers, Saiichi-Sankyo, Astra Zeneca, 8; N. Sugiyama M.D., Ph.D, Pfizer Inc, 1,Pfizer Inc, 3; T. Yoshinaga, Pfizer Inc, 1,Pfizer Inc, 3; K. Togo, Pfizer Inc, 1,Pfizer Inc, 3; J. Geier, Pfizer Inc, 1,Pfizer Inc, 3; M. Boy, Pfizer Inc, 1,Pfizer Inc, 3; C. Connell, Pfizer Inc, 1,Pfizer Inc, 3.

To cite this abstract in AMA style:

Tanaka Y, Takeuchi T, Yamanaka H, Sugiyama M.D. Ph.D N, Yoshinaga T, Togo K, Geier J, Boy M, Connell C. Malignancy Data in Tofacitinib-Treated Japanese Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/malignancy-data-in-tofacitinib-treated-japanese-patients-with-rheumatoid-arthritis/. Accessed .

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