Efficacy and Safety of Dimethyl Fumarate in Patients with Moderate-to-Severe Plaque Psoriasis: Results from a 52-Week Open-Label Phase IV Clinical Trial (DIMESKIN 1)

Abstract

Introduction: Although dimethyl fumarate (DMF) has been approved since 2017 for treatment of moderate-to-severe plaque psoriasis, limited data on its safety and efficacy are available in clinical practice. The objective was to assess the efficacy and safety of DMF in patients with moderate-to-severe plaque psoriasis through 52 weeks in conditions close to real clinical practice.

Methods: DIMESKIN 1 was a 52-week, open-label, phase IV clinical trial conducted at 36 Spanish sites. Adults with diagnosis of moderate-to-severe plaque psoriasis, treated with DMF as per its summary of product characteristics and with ≥ 1 post-baseline Psoriasis Area and Severity Index (PASI) value were included [intention-to-treat (ITT) population]. Efficacy analyses were performed for ITT population and are based on multiple imputation.

Results: Overall, 282 and 274 patients were included in the safety and ITT populations, respectively. At week 24, 46.0%/24.8%/10.9% of patients achieved PASI 75/90/100 response, respectively. At week 52, these percentages were 46.0%/21.9%/10.9%, respectively. Mean body surface area affected decreased from 17.4% to 6.9%/7.3% after 24/52 weeks (p < 0.001, both). A total of 42.9%/49.4% of patients had a Physician's Global Assessment 0-1 at week 24/52, respectively. Mean pruritus visual analogue scale (VAS) significantly decreased after 24 and 52 weeks (p < 0.001, both), with 56.5% and 67.6% of patients, respectively, rating a pruritus VAS < 3. At week 24/52, 61.3%/73.4% patients had a Dermatology Life Quality Index (DLQI) ≤ 5 and 34.7%/32.1% had a DLQI 0-1. The most frequent adverse events were gastrointestinal disorders (mainly diarrhea/abdominal pain in 50.0%/35.1% of patients, respectively), flushing (28.0%), and lymphopenia (31.2%), mostly mild/moderate.

Conclusions: DMF significantly improves main severity and extension indexes and rates, as well as patient-reported outcomes such as pruritus and quality of life in patients with moderate-to-severe psoriasis after 24 weeks of treatment. These improvements are sustained through 52 weeks. The safety profile of DMF is similar to that previously described for fumarates.

Eudract number: 2017-00136840.

Keywords: Clinical practice; Dimethyl fumarate; Efficacy; Psoriasis; Safety.

Fig. 1

Patient flowchart. AE adverse event, ITT intention-to-treat, PASI Psoriasis Area and Severity Index

Fig. 2

Evolution of PASI 50, PASI 75, PASI 90, and PASI 100 responses through week 52. MI multiple imputation, OC observed cases, PASI Psoriasis Area and Severity Index

Fig. 3

PASI score at baseline and weeks 24/52 (a). Evolution of absolute PASI ≤ 1, ≤ 3, and ≤ 5 responses through week 52 (b). MI multiple imputation, OC observed cases, PASI Psoriasis Area and Severity Index

Fig. 4

BSA score at baseline and weeks 24/52 (a). Proportion of patients with PGA 0–1 at weeks 24/52 (b). *One patient had no BSA value at baseline. BSA body surface area, MI multiple imputation, OC observed cases, PGA Physician’s Global Assessment

Fig. 5

Pruritus VAS score at baseline and weeks 24/52 (a). Evolution of mean pruritus VAS (MI and OC) and proportion of patients with pruritus VAS < 3 (OC) through week 52 (b). MI multiple imputation, OC observed cases, VAS visual analogue scale

Fig. 6

DLQI mean score at baseline and weeks 24/52 (a). Proportions of patients (MI) with DLQI ≤ 5 and 0–1 at baseline and weeks 24/52 (b). DLQI Dermatology Life Quality Index, MI multiple imputation, OC observed cases

Fig. 7

PASI score at baseline and weeks 24/52 among systemic-naïve patients. MI multiple imputation, OC observed cases, PASI Psoriasis Area and Severity Index