Quality of life outcomes in adults with moderate-to-severe plaque psoriasis treated with dimethylfumarate (DMF): a post hoc analysis of the BRIDGE study

Abstract

Background: Psoriasis is a chronic inflammatory skin disease associated with quality of life (QoL) impairment. BRIDGE was a randomized, double-blind, phase III study comparing the efficacy and safety of dimethylfumarate (DMF) with a fixed combination of fumaric acid esters (FAE) or placebo for the treatment of moderate-to-severe psoriasis.

Objectives: This post hoc analysis investigated treatment effect on QoL overall and by patient subgroups categorized by disease severity. Week 8 efficacy responses were also investigated as possible predictors of Week 16 Dermatology Life Quality Index (DLQI) outcomes.

Methods: Patients were randomized to receive a maximum daily dose of 720 mg of DMF, FAE (gradual up-titration) or placebo for 16 weeks. Psoriasis Area Severity Index, Body Surface Area, Physician's Global Assessment and DLQI were assessed at baseline, Weeks 8 and 16. DLQI 0-1 indicated 'no effect on patient life'. Associations between baseline severity, Week 16 DLQI and Week 8 efficacy (as observed cases) were also examined.

Results: At baseline, 671 patients were included in the full analysis set (267 randomized to DMF, 273 to FAE and 131 to placebo). DMF was superior to placebo (P < 0.001) and not significantly different to FAE regarding Week 16 DLQI outcomes (P > 0.05). Baseline disease severity did not impact DLQI outcomes at Week 16. In DMF- and FAE-treated patients, Week 8 PASI 50/75 responders reported better DLQI responses at Week 16 vs non-responders (P < 0.05). Week 8 PASI ≤ 3 and/or PGA 0-1 responders were also more likely to report DLQI 0-1 at Week 16 vs non-responders (P < 0.05).

Conclusion: Dimethylfumarate significantly improved DLQI outcomes vs. placebo and was not affected by baseline disease severity. Efficacy responses (PASI 50/75, PASI ≤3 and PGA 0-1) as early as Week 8 were predictive of QoL outcomes at Week 16 in DMF- and FAE-treated patients.

Figure 1

(a) Mean (SD) DLQI and (b) percentage of patients who reported a DLQI 0‐1 response at baseline and Week 16 treated with DMF, FAE combination or placebo. **P < 0.001; ***P < 0.0001. DLQI, Dermatology Life Quality Index; DMF, dimethylfumarate; FAE, fumaric acid ester; SD, standard deviation.

Figure 2

Percentage of patients who reported (a) DLQI 0‐1 and (b) ≥5‐point reduction responses at Week 16 by baseline disease severity, in patients treated with DMF, FAE combination and placebo. No significant differences were observed between disease severity subgroups (P > 0.05). Chi‐square tests. BSA, Body Surface Area; DLQI, Dermatology Life Quality Index; DMF, dimethylfumarate; FAE, fumaric acid ester; PASI, Psoriasis Area and Severity Index; PGA, Physician's Global Assessment.

Figure 3

Percentage of patients who reported DLQI 0‐1 at Week 16 and their corresponding absolute PASI score at Week 16; (a) PASI ≤5, (b) PASI ≤3 and (c) PASI ≤1. DLQI, Dermatology Life Quality Index; DMF, dimethylfumarate; FAE, fumaric acid ester; PASI, Psoriasis Area and Severity Index.

Figure 4

(a) PASI 75 at Week 8 as a predictor of a ≥5‐point reduction in DLQI at Week 16 (percentage of responding patients). (b) PASI75 response at Week 8 as a predictor of DLQI 0‐1 at Week 16 (percentage of responding patients). *P < 0.05; **P < 0.01. Chi‐square tests. DLQI, Dermatology Life Quality Index; DMF, dimethylfumarate; FAE, fumaric acid ester; PASI, Psoriasis Area and Severity Index; PASI 75, 75% reduction in PASI.

Figure 5

(a) PASI ≤3 and (b) PGA 0‐1 at Week 8 as predictors of a DLQI 0‐1 response at Week 16 (percentage of responding patients). *P < 0.05, **P < 0.01, ***P < 0.001 Chi‐square tests. DLQI, Dermatology Life Quality Index; DMF, dimethylfumarate; FAE, fumaric acid ester; PASI, Psoriasis Area and Severity Index; PGA, Physician's Global Assessment.