AB0495 Post-marketing surveillance of tofacitinib in japanese patients with rheumatoid arthritis: an interim report of safety data
Authors: N. Tamura, M. Kuwana, T. Atsumi, S. Takei, M. Harigai, T. Fujii, H. Matsuno, T. Mimori, S. Momohara, K. Yamamoto, K. Nomura, Y. Endo, N. Sugiyama, T. Hirose, Y. Morishima, N. Yoshii, M. Takagi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib have been shown in patients (pts) with RA in global Phase (P)2, P3 and a long-term extension (LTE) study and in 2 P2 and 1 LTE study in Japanese pts. <h3>Objectives</h3> To evaluate safety of tofacitinib following drug approval in Japanese pts with RA using all-case post-marketing surveillance (PMS) data. <h3>Methods</h3> An interim analysis (IA) of safety data from an ongoing 3 year PMS study was conducted (5 Nov 2017 data-cut). All Japanese RA pts receiving tofacitinib were prospectively registered in the PMS study. All adverse events (AEs) were collected during tofacitinib treatment. Follow-up surveillance after discontinuation was conducted for serious infection events (SIEs; 1 year), malignancy and death (3 years). For all AEs and serious AEs, 6 month IA data was used. For AEs of special interest, all-period data (up to 36 months) was used to calculate cumulative incidence rates (IRs: pts with events/100 pt-years [yrs]) over time for herpes zoster (HZ) and SIEs during treatment +28 days and for malignancies during the full observation period. <h3>Results</h3> Overall, 3929 tofacitinib-treated pts with 1704.1 pt-yrs of exposure were included in the 6 month IA of safety: 80.5% were female, mean age was 62.7 years, with 32.6% of pts≥70 years. Of these, 892 pts (22.7%) discontinued treatment, mainly due to AEs (351 pts; 8.9%) or lack of effectiveness (335 pts; 8.5%). At least one AE was observed in 1313 pts (33.4%); infections were observed in 493 pts (12.5%). The most frequent AEs were HZ (145 pts; 3.7%) and abnormal hepatic function (72 pts; 1.8%). SAEs occurred in 287 pts (7.3%); the most frequent SAEs were HZ (24 pts; 0.6%) and pneumonia/bacterial pneumonia (33 pts; 0.8%). SIEs occurred in 130 pts (3.3%). Malignancy (all causality) was reported in 25 pts (0.6%); lymphoma/lymphoproliferative disorder occurred in 5 pts (0.1%) and breast cancer in 3 pts (0.08%). There were 21 deaths (0.5%) during the 6 month period. The most common causes of death (including pts with multiple causes listed) were infection (6 cases) and malignancy (5 cases). For AEs of special interest from all-period data the IR of HZ (serious and non-serious) was 6.81 (264 pts; 3876 pt-yrs), the IR of SIEs was 5.38 (212 pts; 3941 pt-yrs) and the IR of malignancy was 1.25 (61 pts; 4874 pt-yrs). <h3>Conclusions</h3> This IA of tofacitinib PMS in Japan did not reveal any new or unexpected safety signals vs the tofacitinib RA clinical trials. IRs for HZ and malignancy were similar to IRs in clinical trials of tofacitinib in Japanese RA pts and the SIE IR was within the range reported in PMS of biologic treatments. Continuous monitoring of SAEs is required until the final PMS results. <h3>Acknowledgements</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by A MacLachlan of CMC and funded by Pfizer Inc. <h3>Disclosure of Interest</h3> N. Tamura Grant/research support from: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Takeda, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Janssen, Mitsubishi-Tanabe, M. Kuwana Grant/research support from: Ayumi, Chugai, Eisai, Mitsubishi-Tanabe, Ono, Pfizer Inc, Speakers bureau: Astellas, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Ono, Pfizer Inc, UCB, T. Atsumi Grant/research support from: Alexion, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Sanofi Scholarship donations from: Bayer, Daiichi-Sankyo, Takeda, Speakers bureau: AbbVie, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, Takeda, Pfizer Inc, UCB Japan, S. Takei Grant/research support from: Chugai, Eisai, Mitsubishi-Tanabe, Takeda, Speakers bureau: Asahi-kasei, Ayumi, Chugai, Mitsubishi-Tanabe, Ono, M. Harigai Grant/research support from: Eisai, Takeda, Teijin, Consultant for: AbbVie, Ayumi, Bristol-Myers Squibb, Chugai, Janssen, Pfizer Inc, Paid instructor for: Takeda, T. Fujii Shareholder of: AbbVie, Ayumi, Bristol-Myers Squibb, Chugai, Janssen, Eisai, Mitsubishi-Tanabe, Ono, Grant/research support from: Eisai, Mitsubishi-Tanabe, Ono, Daiichi-Sankyo, Pfizer Japan Inc, Speakers bureau: AbbVie, Mitsubishi-Tanabe, Ono, Pfizer Japan Inc., H. Matsuno Consultant for: Ayumi, Meiji Seika, Mochida, Nichi-Iko, T. Mimori Grant/research support from: Astellas, Ayumi, Chugai, Daiichi-Sankyo, Eisai, MSD, Mitsubishi-Tanabe, Sanofi, Taisho Toyama, Speakers bureau: Astellas, Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi-Tanabe, S. Momohara Speakers bureau: AbbVie, Bristol-Myers Squibb, Eisai, Janssen, Pfizer Japan Inc, Ono, Takeda, Mitsubishi-Tanabe, K. Yamamoto Grant/research support from: AbbVie, Astellas, Ayumi, Chugai, Eisai, Mitsubishi-Tanabe, Nippon Kayaku, Pfizer Inc, Takeda, Taisho Toyama, UCB, Teijin, Speakers bureau: Asahi-kasei, AstraZeneca, Ayumi, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Janssen, UCB, Mitsubishi-Tanabe, Pfizer Inc, Sanofi, Sumitomo Dainippon, Taisho-Toyama, Takeda, Teijin, K. Nomura Employee of: Pfizer Japan Inc, Y. Endo Employee of: Pfizer Japan Inc, N. Sugiyama Employee of: Pfizer Japan Inc, T. Hirose Employee of: Pfizer Japan Inc, Y. Morishima Employee of: Pfizer Japan Inc, N. Yoshii Employee of: Pfizer Japan Inc, M. Takagi Grant/research support from: Kaken, Taisho-Toyama, Eizai, Hisamitsu, Chugai, Pfizer Inc, Kyocera, Nihon Zoki, MSD, Astellas, AbbVie, Daiichi-Sankyo, Teijin, Takeda, Mitsubishi-Tanabe, Shionogi