Tofacitinib in Patients With Moderate-to-severe Chronic Plaque Psoriasis

Long-term Safety and Efficacy in an Open-label Extension Study

F. Valenzuela; N.J. Korman; R. Bissonnette; N. Bakos; T.-F. Tsai; M.K. Harper; W.C. Ports; H. Tan; A. Tallman; H. Valdez; A.C. Gardner


The British Journal of Dermatology. 2018;179(4):853-862. 

In This Article

Abstract and Introduction


Background: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported.

Objectives: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis.

Methods: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75).

Results: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52–62% of patients and PASI 75 by 56–74% of patients at each study visit through month 54.

Conclusions: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).


Tofacitinib is an oral Janus kinase (JAK) inhibitor. JAK inhibition by tofacitinib blocks signalling through several cytokines that are integral to lymphocyte function.[1] Tofacitinib attenuates pathological immune pathways in patients with psoriasis through rapid reduction of keratinocyte JAK/signal transducer activator of transcription signalling, inhibition of the interleukin–23/T-helper 17 pathway and removal of keratinocyte-induced cytokine signalling, resulting in reduction of pathological dendritic cell and T-cell numbers to nonlesional levels.[2]

The efficacy and safety of tofacitinib 5 and 10 mg twice daily (q12h) in patients with moderate-to-severe plaque psoriasis has been demonstrated in phase II[3] and global phase III[4–7] trials of up to 56 weeks' duration, and in this long-term extension (LTE) study based on interim data with efficacy end points reported through 24 months and safety reported over 33 months of exposure.[7] The efficacy and safety of tofacitinib has also been studied in several immune-mediated inflammatory diseases, including rheumatoid arthritis;[8–13] Crohn disease (NCT01470599);[14,15] psoriatic arthritis (NCT01976364);[16,17] ulcerative colitis;[18,19] and ankylosing spondylitis.[20]

The management of patients with moderate-to-severe plaque psoriasis often requires long-term maintenance treatment.[21,22] Here we report the final safety and efficacy data from the LTE study of tofacitinib in chronic plaque psoriasis.