Oral Dimethyl Fumarate Improves All Disease Classification Criteria in Plaque Psoriasis

Treatment with oral dimethyl fumarate led to significant improvements of all criteria for disease classification upgrade criteria in patients with plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.¹

Even when discontinued prior to week 52 of the study, patients meeting the upgrade criteria for moderate to severe disease classification exhibited substantial improvements in involvement of physical areas and pruritus, among others.

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Background and Methods

Approved in Germany in 1994, dimethyl fumarate and its metabolite monomethyl fumarate have demonstrated a well-established safety and efficacy profile for treating moderate to severe psoriasis.² Its long-term effectiveness and safety in this indication were confirmed over 52 weeks in several studies, including the 2022 SKILarence in long-term treatment (SKILL) study.³

Expanding upon SKILL's findings, researchers involved in the present study sought to assessed dimethyl fumarate's effects on patients with low body surface area (BSA) and Psoriasis Area and Severity Index (PASI) scores and moderate to severe plaque psoriasis based on upgrade criteria.

The 52-week, open-label, non-randomized, multicenter observational study, known as UPSKIL, was conducted in Germany from July 2019 to February 2022. Adult patients with plaque psoriasis and low PASI/BSA scores meeting criteria for moderate to severe disease were included in the study if treatment with dimethyl fumarate was indicated. Patients with a history of prior treatment and inadequate response with fumaric acid esters were excluded from participation.

Effectiveness of treatment was measured using PASI, BSA, the Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and ItchyQoL [Quality of Life] scores at baseline and 12, 24, 36, and 52 weeks, with specific assessments made for different psoriasis types and most severely affected areas. At each visit described above, researchers monitored and recorded safety and adverse events.

Findings

After excluding 23 patients due to protocol violations, 180 patients were included in the study's effectiveness analysis. Of these, 145 (80.6%) left the study early due to reasons such as lost 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. Only 35 patients (19.4%) completed 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%), and 42.8% had comorbid conditions.

Patients started treatment with dimethyl fumarate at 30 mg/day, with dosage increasing up to 720 mg/day if tolerated. Average daily doses were 30 mg at baseline, increasing 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 a 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 improvement across all upgrade criteria, 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 due to upper abdominal pain, diarrhea, lymphopenia, and flushing.

Conclusions

"To the best of our knowledge, 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 of the study included its noninterventional design, absence of a comparator group, and its high drop-out rate.

"Taken together, the real-world data collected in this noninterventional study provided additional insights on patients receiving DMF due to upgrade criteria," wrote study authors. "In consequence of their long-term presence in the market, [fumaric acid esters] has become an established daily tool for dermatologists to treat patients burdened with comorbidities and psoriasis lesions in difficult-to-treat areas."

References

1. Gerdes S, Al Ghazal P, Diemert S, Termeer C. Effect of dimethyl fumarate in patients with plaque psoriasis meeting the upgrade criteria required for moderate-to-severe disease classification. J Eur Acad Dermatol Venereol. Published online July 3, 2024. https://doi.org/10.1002/jvc2.504
2. Mrowietz U, Barker J, Boehncke WH, Iversen L, Kirby B, Naldi L, et al. Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a European expert consensus. J Eur Acad Dermatol Venereol. 2018; 32(suppl 3): 3–14.
3. Augustin M, Landeck L, Diemert S, Asadullah K, Hammann U, Ertner K, et al. Long-term treatment with dimethyl fumarate for plaque psoriasis in routine practice: good overall effectiveness and positive effect on impactful areas. Dermatol Ther. 2022; 12(5): 1121–1131. https://doi.org/10.1007/s13555-022-00714-0