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THU0187 Safety of Tofacitinib, An Oral Janus Kinase Inhibitor: Integrated Data Analysis from The Global Chronic Plaque Psoriasis Clinical Trials
  1. R.G.B. Langley1,
  2. A.D. Cohen2,
  3. P. Foley3,
  4. C.E.M. Griffiths4,
  5. M. Lebwohl5,
  6. C. Leonardi6,
  7. K. Winthrop7,
  8. J. Proulx8,
  9. S.T. Rottinghaus9,
  10. R. Wolk8,
  11. J.R. Thompson8,
  12. S. Tatulych8,
  13. L. Mallbris10,
  14. R. Swanson11
  1. 1Department of Medicine, Dalhousie University, Halifax, Canada
  2. 2Department of Quality Measures and Research, Clalit Health Services, Tel Aviv, Israel
  3. 3University of Melbourne, Parkville, Australia
  4. 4Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester, United Kingdom
  5. 5Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York
  6. 6St Louis University Department of Dermatology, St Louis
  7. 7Oregon Health and Science University, Portland
  8. 8Pfizer Inc
  9. 9Formerly of Pfizer Inc, Groton
  10. 10Formerly of Pfizer Inc, Collegeville
  11. 11Pfizer Inc, New York, United States

Abstract

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis that is being investigated for psoriasis.

Objectives To report pooled trial safety data in patients with psoriasis to expand knowledge around the safety profile of tofacitinib in inflammatory diseases.

Methods The 1-year randomised controlled trials (RCT) group included patients with psoriasis who received ≥1 dose of tofacitinib 5 or 10 mg BID in three 1-year Phase 3 RCTs. The integrated safety group included patients with psoriasis who received ≥1 dose of tofacitinib in four Phase 3 studies (5 or 10 mg BID) or a long-term extension (LTE) study. In the LTE study, patients entered following one Phase 2 study or the Phase 3 studies and received 10 mg BID (for 3 months), then 5 or 10 mg BID (ongoing, database not locked, data cut-off April 4, 2014). Incidence rates (IR; patients with events/100 patient-years) were calculated for the 1-year RCT and integrated safety groups. For the integrated safety group, data were pooled across doses.

Results In the 1-year RCT group, 2436 patients received tofacitinib (5 mg BID, n=1217; 10 mg BID, n=1219), with a median of 253 days of tofacitinib exposure (range: 1–431, first and third quartiles: 168, 364). In the integrated safety group, 3623 patients received tofacitinib, with a median of 527 days of tofacitinib exposure (range: 1–1344, first and third quartiles: 261, 766). Serious infection IRs were 1.37 and 2.42 respectively for 5 and 10 mg BID in the 1-year RCT group, and 1.68 in the integrated safety group. Herpes zoster IRs were 1.00 and 2.32 for 5 and 10 mg BID in the 1-year RCT group, and 2.55 in the integrated safety group. Malignancy (excluding non-melanoma skin cancer [NMSC]) IRs were 1.12 and 0.81 for 5 and 10 mg BID in the 1-year RCT group, and 1.00 in the integrated safety group. NMSC IRs were 0.63 and 1.27 for 5 and 10 mg BID in the 1-year RCT group, and 0.74 in the integrated safety group. Major adverse cardiovascular event IRs were 0.50 and 0.23 for 5 and 10 mg BID in the 1-year RCT group, and 0.37 in the integrated safety group. In the 1-year RCT group, 95% confidence intervals for 10 vs 5 mg BID hazard ratios included 1 for each of these events.

Conclusions Serious infection, herpes zoster and NMSC IRs were numerically, but not statistically, higher with 10 vs 5 mg BID. IRs were similar in the RCT group and the integrated safety group, indicating that IRs are stable over time. Tofacitinib was well tolerated in patients with plaque psoriasis – including up to 44 months of exposure for some patients in the ongoing LTE study at data cut-off.

Acknowledgement Previously presented (Langley R et al. J Invest Dermatol 2015; 135 (S3): 39). This study was funded by Pfizer Inc. Editorial support was provided by Complete Medical Communications, and funded by Pfizer Inc.

Disclosure of Interest R. G. Langley Grant/research support from: AbbVie, Amgen, Celgene, Leo, Eli Lilly, Merck, Novartis, Pfizer Inc, Consultant for: AbbVie, Amgen, Celgene, Leo, Eli Lilly, Merck, Novartis, Pfizer Inc, Speakers bureau: AbbVie, Amgen, Celgene, Leo, Merck, Novartis, Pfizer Inc, A. Cohen Grant/research support from: Novartis, AbbVie, Consultant for: Pfizer Inc, Novartis, AbbVie, Janssen, P. Foley Grant/research support from: Galderma, Leo/Peplin, Ascent, Abbott/AbbVie, Janssen-Cilag, Wyeth/Pfizer Inc, Novartis, Roche, Consultant for: Galderma, Leo/Peplin, Ascent, Clinuvel, Janssen-Cilag, Eli Lilly, Australian Ultraviolet Services, Roche, Speakers bureau: CSL, Galderma, 3M/iNova/Valeant, Leo/Peplin, Ascent, Clinuvel, GSK/Stiefel, Abbott/AbbVie,Biogen Idec, Janssen-Cilag, Merck Serono, Schering-Plough/MSD, Wyeth/Pfizer Inc, Amgen, Novartis, Eli Lilly, Celgene, Roche, Aspen, BMS, C. E. Griffiths Grant/research support from: AbbVie, Actelion, Biotest, Celgene, Eli Lilly, Incyte, Janssen, Leo, MSD, Novartis, Pfizer Inc, Sandoz, Stiefel U.K., Trident, Zymogenetics and UCB, M. Lebwohl Consultant for: AbGenomics, Amgen, Anacor, Canfite Biopharma, Celgene, Clinuvel, Coronado Biosciences, Dermipsor, Ferndale, Lilly, Janssen Biotech, Leo, Merz, Novartis, Pfizer Inc, C. Leonardi Grant/research support from: AbbVie, Amgen, Anacor, Celgene, Coherus, Eli Lilly, Galderma, Janssen, Merck, Pfizer Inc, Sandoz, Stiefel, Leo, Novartis and Tolmar, Consultant for: AbbVie, Amgen, Dermira, Janssen, Boehringer-Ingleheim, Eli Lilly, Leo, Sandoz, UCB and Pfizer Inc, Speakers bureau: AbbVie, K. Winthrop Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, J. Proulx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Rottinghaus Shareholder of: Pfizer Inc, Employee of: Pfizer Inc (at the time of analysis), R. Wolk Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Thompson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Tatulych Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Mallbris Shareholder of: Pfizer Inc, Employee of: Pfizer Inc (at the time of analysis), R. Swanson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

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