Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial

Abstract

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.

Keywords: Janus kinase inhibitor; Japanese; oral medicine; plaque psoriasis; tofacitinib.

Figure 1

Proportion of patients achieving (a) PASI‐75 and (b) PGA response through week 52 (FAS, NRI). *P < 0.01; **P < 0.001; ***P < 0.0001 vs placebo, Barnard's test. Patients initially assigned to placebo moved to active treatment at week 16; only two patients advanced from placebo (to tofacitinib 5 mg b.i.d.), both achieved PASI‐75 and PGA response at all subsequent time points, data are not shown for weeks 20–52 for these patients. At week 28, patients who did not achieve PASI‐75 or PGA response were withdrawn from the study. Eligible patients could enroll in an open‐label LTE study; otherwise, a follow‐up visit was performed 2–4 weeks after the patient's last dose of study medication. CI, confidence interval; FAS, full analysis set; LTE, long‐term extension; NRI, non‐responder imputation; PASI, Psoriasis Area and Severity Index; PASI‐75, 75% or more reduction from baseline in PASI score; PGA, Physician's Global Assessment; PGA response, “clear” or “almost clear”.

Figure 2

Change from baseline in (a) ISI and (b) DLQI, and (c) percent change from baseline in NAPSI over 52 weeks (FAS, observed cases). Patients initially assigned to placebo moved to active treatment at week 16; only two patients advanced from placebo (to tofacitinib 5 mg b.i.d.), data are not shown for weeks 20–52 for these patients. At week 28, patients who did not achieve PASI‐75 or PGA response were withdrawn from the study. Eligible patients could enroll in an open‐label LTE study; otherwise, a follow‐up visit was performed 2–4 weeks after the patient's last dose of study medication. DLQI, Dermatology Life Quality Index; FAS, full analysis set; ISI, Itch Severity Item; LTE, long‐term extension; NAPSI, Nail Psoriasis Severity Index; PASI‐75, 75% or more reduction from baseline in PASI score; PGA, Physician's Global Assessment; SE, standard error.

Figure 3

Change from baseline in (a) LDL‐C and (b) HDL‐C over 52 weeks (FAS, observed cases). Patients initially assigned to placebo moved to active treatment at week 16; only two patients advanced from placebo (to tofacitinib 5 mg b.i.d.), data are not shown for weeks 20–52 for these patients. FAS, full analysis set; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SE, standard error.