Effect of tofacitinib withdrawal and re‐treatment on patient‐reported outcomes: results from a Phase 3 study in patients with moderate to severe chronic plaque psoriasis

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re‐treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re‐treatment was effective in patients with chronic plaque psoriasis. OBJECTIVES: To describe the effects of tofacitinib withdrawal/re‐treatment on health‐related quality of life (HRQoL) and disease symptoms measured by patient‐reported outcomes (PROs). METHODS: The study was divided into initial treatment, treatment withdrawal, and re‐treatment periods. Initial treatment: patients were randomized to receive tofacitinib 5 (n = 331) or 10 mg (n = 335) BID for 24 weeks. Treatment withdrawal: patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline and Physician's Global Assessment of ‘clear’/‘almost clear’ at Week (W)24 received placebo (withdrawal) or the previous dose (continuous treatment). Re‐treatment: at relapse (> 50% loss of W24 PASI response) or at W40, patients received their initial tofacitinib dose. PROs included: Dermatology Life Quality Index (DLQI), Itch Severity Item (ISI), Short Form‐36 (SF‐36) and Patient's Global Assessment (PtGA). RESULTS: After initial treatment with tofacitinib 5 and 10 mg BID, substantial and significant improvements were reported for mean DLQI (baseline: 12.6 and 12.6; W24: 5.1 and 2.6) and ISI (baseline: 6.7 and 6.9; W24: 2.9 and 1.6). Patients continuously treated with tofacitinib 5 and 10 mg BID maintained those improvements through Week 56 (DLQI: 3.0 and 2.1; ISI: 2.3 and 1.4). By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re‐treatment (W56, DLQI: 3.4 and 2.4; ISI: 2.2 and 1.6). Similar results were reported for PtGA and SF‐36. CONCLUSION: Continuous tofacitinib treatment provided sustained improvement in HRQoL and disease symptoms. Patients randomized to treatment withdrawal lost initial improvements. Upon re‐treatment, improvements were recaptured to levels comparable to those seen with continuous treatment.