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SAT0439 Integrated safety summary of tofacitinib in psoriatic arthritis clinical studies
  1. G Burmester1,
  2. O FitzGerald2,
  3. K Winthrop3,
  4. G Williams4,
  5. VF Azevedo5,
  6. WFC Rigby6,
  7. K Kanik7,
  8. C Wang7,
  9. P Biswas8,
  10. T Jones9,
  11. S Menon7,
  12. N Palmetto8,
  13. R Rojo7
  1. 1Charité - University Medicine Berlin, Berlin, Germany
  2. 2Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland
  3. 3Oregon Health and Science University, Portland, OR
  4. 4Williams Cancer Drug Consulting LLC, Wayne, NJ, United States
  5. 5Universidade Federal do Paraná, Curitiba, Brazil
  6. 6Geisel School of Medicine at Dartmouth, Lebanon, NH
  7. 7Pfizer Inc, Groton, CT
  8. 8Pfizer Inc, New York, NY
  9. 9Pfizer Inc, Collegeville, PA, United States

Abstract

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA).

Objectives To describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies.

Methods Data were analysed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analysed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analysed over 12 months in pts randomised to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomised to PBO were excluded from this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiac events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications.

Results C1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomised to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomised to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]) and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]).

Conclusions Tofacitinib was well tolerated in pts with PsA, with a safety profile consistent to that seen in RA; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA.

Acknowledgements These studies were sponsored by Pfizer Inc. Editorial support was provided by C Viegelmann of CMC and was funded by Pfizer Inc.

Disclosure of Interest G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, MSD, MedImmune, Novartis, Pfizer Inc, Sanofi, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, G. Williams Consultant for: Pfizer Inc, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Novartis, Pfizer Inc, Serono, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Jones Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Palmetto Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Rojo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

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