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

Abstract

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 By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re-treatment (W56, DLQI: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.

Figure 1

Study design and patient numbers. *Patients were evaluated at Weeks 28, 32, 36 and 40. If patients experienced > 50% loss of Week 24 PASI response at any time point, they advanced to the re‐treatment period. All patients advanced to the re‐treatment period by Week 40. ^†Study duration was 56 weeks. If a patient entered the re‐treatment period before Week 40, the duration of the re‐treatment period was > 16 weeks; efficacy evaluations were carried out after 16 weeks of re‐treatment. BID, twice daily; PASI, Psoriasis Area and Severity Index; PASI75, ≥ 75% reduction in PASI score from baseline; PGA, Physician's Global Assessment.

Figure 2

Mean score over time for (a) ISI and (b) DLQI (Full analysis set, observed case). *Patients experiencing > 50% loss of Week 24 PASI response advanced to re‐treatment before Week 40. BID, twice daily; DLQI, Dermatology Life Quality Index; ISI, Itch Severity Item; PASI; Psoriasis Area and Severity Index; SE, standard error; wk, week.

Figure 3

(a) Proportion of patients achieving ISI ≤ 1 (little or no pruritus) during the initial treatment period, among patients with baseline ISI > 1; (b) Proportion of patients maintaining ISI ≤ 1 during treatment withdrawal, among patients with ISI ≤ 1 at the start of the withdrawal period; (c) Proportion of patients achieving ISI ≤ 1 during the re‐treatment period, among patients with ISI > 1 at the start of the re‐treatment period (Full analysis set, non‐responder imputation). BID, twice daily; ISI, Itch Severity Item; SE, standard error.

Figure 4

(a) Proportion of patients achieving DLQI ≤ 1 (little to no impact of psoriasis on quality of life) during the initial treatment period, among patients with baseline DLQI > 1; (b) Proportion of patients maintaining DLQI ≤ 1 during treatment withdrawal, among patients with DLQI ≤ 1 at the start of the withdrawal period; (c) Proportion of patients achieving DLQI ≤ 1 during the re‐treatment period, among patients with DLQI > 1 at the start of the re‐treatment period (Full analysis set, non‐responder imputation). BID, twice daily; DLQI, Dermatology Life Quality Index; SE, standard error.

Figure 5

Percentage of patients within each PtGA assessment category in (a) the initial treatment period; (b) the treatment‐withdrawal period; (c) the re‐treatment period (Full analysis set, observed case). BID, twice daily; PtGA, Patient's Global Assessment.