Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double-blind, phase 3 study

Abstract

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double-blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open-label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end-points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of "clear" or "almost clear" (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty-seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.

Keywords: Japan; kinase inhibitor; plaque psoriasis; psoriatic arthritis; tofacitinib.

Figure 1

Study design. ^†Stratified by type of psoriasis at randomization. BL, baseline; FU, follow‐up.

Figure 2

Patient disposition. ^†Five patients in the tofacitinib 10 mg b.i.d. group had both plaque psoriasis and psoriatic arthritis. AEs, adverse events; FAS, full analysis set; SAS, safety analysis set.

Figure 3

Proportion of patients with moderate to severe plaque psoriasis achieving (a) PASI75, (b) PASI90 and (c) PGA response of “clear” or “almost clear” over time, according to initially randomized dose group (NRI). *P < 0.05 versus tofacitinib 5 mg b.i.d.; FU, follow‐up; NRI, non‐responder imputation; PASI, Psoriasis Area and Severity Index; PGA, Physician's Global Assessment; SE, standard error.

Figure 4

Proportion of patients with psoriatic arthritis who achieved (a) ACR20, (b) ACR50 and (c) ACR70 response, according to initially randomized dose group (NRI). *P < 0.05 versus tofacitinib 5 mg b.i.d. ACR, American College of Rheumatology response criteria; FU, follow‐up; NRI, non‐responder imputation; SE, standard error.

Figure 5

Change from baseline in laboratory parameters through follow‐up, for (a) neutrophil counts, (b) lymphocyte counts, (c) hemoglobin levels, (d) creatine phosphokinase, (e) LDL cholesterol, (f) HDL cholesterol and (g) LDL/HDL ratio, by initially randomized dose group (safety analysis set). HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; SD, standard deviation.