Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. Psoriasis impacts on physical and psychological well-being; improvements in health-related quality of life (HRQoL) with etanercept in psoriasis are well documented.

Objective: To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non-inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591).

Methods: Adults with moderate to severe chronic plaque psoriasis were randomized 3:3:3:1 to tofacitinib 10 or 5 mg twice daily (BID), etanercept 50 mg twice weekly or placebo, for 12 weeks. Patient-reported outcomes (PROs) included Dermatology Life Quality Index (DLQI), Itch Severity Item and Patient Global Assessment of psoriasis.

Results: At baseline, 83.4% (911/1092) of patients had a DLQI score ranging between 6 and 30, indicating a substantial burden of disease. By Week 12, 47.3%, 43.6% and 30.9% of patients in the tofacitinib 10 mg BID, etanercept and tofacitinib 5 mg BID groups, respectively, had a DLQI score of 0 or 1 (no effect of psoriasis on QoL) vs. 7.8% for placebo (all P < 0.0001). Tofacitinib significantly reduced itch vs. placebo (P < 0.05 both doses) and etanercept (P < 0.0001 both doses) within 1 day of starting treatment. Furthermore, reductions in itch were greater with tofacitinib 10 mg BID, vs. etanercept, at Weeks 2-12 (all time points P < 0.05). At Week 2, an Itch Severity Item score of 'little or no itch' was more frequent with tofacitinib 10 mg (68.6%) vs. etanercept (57.4%) and placebo (12.2%), and the PtGA response rate was significantly greater with tofacitinib 10 mg vs. placebo (P < 0.05).

Conclusion: Oral tofacitinib provided significant improvements across multiple PROs by Week 12. Improvements with tofacitinib 10 mg BID were comparable to etanercept, and improvements in itch were greater and more rapid with tofacitinib 10 mg BID.

Figure 1

Proportion of patients in DLQI categories at baseline and Week 12, categorized according to the effect of the disease on patients’ lives as per previously described classification19 (FAS, observed cases). BID, twice daily; BIW, twice weekly; DLQI, Dermatology Life Quality Index; FAS, full analysis set.

Figure 2

Proportion of patients at baseline, Week 4 and Week 12 with a DLQI score of ≤ 1, indicating ‘no effect of psoriasis on quality of life’ (FAS, NRI). *P < 0.05, ***P < 0.0001 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full analysis set; DLQI, Dermatology Life Quality Index; NRI, non‐responder imputation; SE, standard error.

Figure 3

LS mean change in itch (measured by ISI) from (a) baseline to Day 15 (patient diary entries) and (b) from Week 2 to Week 12 (clinic assessments) (FAS, observed cases). The last patient diary entry was scheduled for the evening before the Week 2 visit. However, not all patients completed the diary for the entirety of the intended period. Also, the window for the Week 2 visit was Day 15 ± 3 days; hence, the Week 2 visit did not necessarily take place on Day 15 for all participants. The Week 2 assessment was made for all patients at the clinic, and these differences account for the apparent difference in ISI values between Day 15 and Week 2. Days 1–15: tofacitinib 5 mg BID N = 291, tofacitinib 10 mg BID N = 296, etanercept N = 290, placebo N = 104. Week 2–12: tofacitinib 5 mg BID N = 304, tofacitinib 10 mg BID N = 306, etanercept N = 304, placebo N = 107. *P < 0.05, **P < 0.001, ***P < 0.0001 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full analysis set; ISI, itch severity item; LS, least squares; SE, standard error.

Figure 4

Proportion of patients with a baseline ISI score > 1 who reported ‘little or no itch’ (score of 0 or 1) at a subsequent visit (FAS, NRI). *P < 0.05, ***P < 0.0001 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full analysis set; ISI, itch severity item; NRI, non‐responder imputation; SE, standard error.

Figure 5

Mean (SE) proportion of patients with a PtGA score of 0 ‘clear’ or 1 ‘almost clear’ (FAS, NRI). *P < 0.05, ***P < 0.0001 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full analysis set; NRI, non‐responder imputation; PtGA, Patient Global Assessment; SE, standard error.