Treatment with oral dimethyl fumarate has led to notable improvements in disease classification criteria for patients with plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology. The study found that even when the medication was discontinued before week 52, patients with moderate to severe disease classification saw significant enhancements in physical symptoms and pruritus.
Background and Methods
Dimethyl fumarate, approved in Germany in 1994, along with its metabolite monomethyl fumarate, has a well-documented safety and efficacy profile for treating moderate to severe psoriasis. This long-term efficacy and safety were reaffirmed over 52 weeks in various studies, including the 2022 SKILarence in long-term treatment (SKILL) study.
Building on SKILL’s findings, researchers aimed to evaluate dimethyl fumarate’s impact on patients with low body surface area (BSA) and Psoriasis Area and Severity Index (PASI) scores, focusing on those classified with moderate to severe plaque psoriasis.
The 52-week, open-label, non-randomized, multicenter observational study, known as UPSKIL, was conducted in Germany from July 2019 to February 2022. It included adult patients with plaque psoriasis and low PASI/BSA scores who met the criteria for moderate to severe disease and were indicated for dimethyl fumarate treatment. Patients with a history of prior treatment and inadequate response to fumaric acid esters were excluded.
Effectiveness was measured using PASI, BSA, the Dermatology Life Quality Index (DLQI), Physician’s Global Assessment (PGA), and ItchyQoL scores at baseline and at 12, 24, 36, and 52 weeks. Researchers assessed different psoriasis types and the most severely affected areas at each visit, while also monitoring safety and adverse events.
Findings
After excluding 23 patients due to protocol violations, 180 patients were included in the effectiveness analysis. Among these, 145 patients (80.6%) discontinued the study early for reasons such as loss to follow-up (28.9%), withdrawal of consent (1.1%), end of therapy (50.6%), and other reasons (1.7%). Intolerance was the primary reason for discontinuation, affecting 71 patients, with only 35 patients (19.4%) completing the study through week 52.
At baseline, the average PASI score was 5.7, BSA was 6.2, DLQI was 12.7, and PGA was 2.7, indicating mild severity. Most patients had visible psoriasis (86.1%) and pruritus (81.1%), with 42.8% having comorbid conditions.
Patients began treatment with dimethyl fumarate at 30 mg/day, increasing to 720 mg/day if tolerated. The average daily dose was 30 mg at baseline, rising to 307 mg at month 3, and decreasing to 251 mg by month 12. Nearly all patients used additional topical therapies during the study.
The proportion of patients achieving PASI <3 improved from 7.9% to 55.3% (last observation carried forward) and from 10.0% to 91.9% (observed cases) by week 52. DLQI scores indicating minimal impact on quality of life rose from 17.4% to 52.1% (last observation carried forward) and from 16.8% to 85.3% (observed cases). PGA scores showed significant improvements, with reductions in severity and increases in clear/almost clear classifications over time.
Over half of the patients (51.2%) reported at least one adverse drug reaction, with common reactions including diarrhea (16.3%), flushing (14.8%), upper abdominal pain (14.3%), and lymphopenia (12.3%). Seven serious adverse events were reported in 3 patients (1.5%). A total of 84 patients (41.4%) discontinued dimethyl fumarate due to adverse events, primarily upper abdominal pain, diarrhea, lymphopenia, and flushing.
Conclusions
“This study is the first to assess the effect of systemic treatment in patients with mild somatic disease and presence of upgrade criteria under real-world conditions,” according to study authors Gerdes et al.
Potential limitations included its non-interventional design, absence of a comparator group, and a high dropout rate.
“Real-world data collected in this non-interventional study provided additional insights on patients receiving DMF due to upgrade criteria,” the authors concluded. “Due to their long-term presence in the market, fumaric acid esters have become an established daily tool for dermatologists treating patients with comorbidities and psoriasis lesions in difficult-to-treat areas.”
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