Objective: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated for psoriasis. This study assessed the relationship between pruritus and clinical signs of psoriasis (assessed by Physician's Global Assessment [PGA]) in patients with moderate-to-severe chronic plaque psoriasis receiving tofacitinib.
Methods: In this 16-week (12-week treatment period, 4-week observation period), double-blind, placebo-controlled, phase IIb study (NCT00678210), 197 patients were randomized to tofacitinib 2, 5 or 15 mg BID, or placebo. Pruritus was patient assessed using the Itch Severity Score (ISS), a 0-10 (10=worst itching) rating scale recorded daily from baseline to week 2 and at study visits. Mediation modeling was used to determine relationships between ISS (average score weeks 2-12), PGA (average score weeks 2-12) and treatment groups.
Results: Mediation analysis showed that 70.2-80.5% (p<0.001 versus placebo) of tofacitinib's effect on pruritus was direct, and mostly independent of improvements in erythema, induration and scaling. ISS measurements had acceptable test-retest reliability. Correlation analyses with clinical outcomes supported the validity of the ISS as a pruritus measure.
Conclusions: Tofacitinib has a direct, beneficial effect on patient-reported pruritus independent from improvements in clinician-reported psoriasis severity signs. The ISS demonstrated favorable psychometric characteristics, supporting its use as a pruritus assessment tool.
Keywords: Erythema; induration; mediation modeling; plaque psoriasis; pruritus; scaling; tofacitinib.