Even though fumaric acid esters are increasingly considered to be a suitable, even a first-line, systemic treatment for moderate to severe psoriasis in some parts of Europe, the evidence supporting their use is sparse and of low quality, according to a report published online in the British Journal of Dermatology.

Fumarates were introduced as anti-psoriasis agents decades ago in Germany. The agents are thought to exert immunomodulating, antiproliferative, and antiangiogenic effects, and they are frequently used off label for psoriasis in the Netherlands and the United Kingdom, said Dr. Deepak M.W. Balak of the department of dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.

To summarize the clinical evidence for this treatment, the investigators performed a systematic review of publications, identifying 68 studies that reported the clinical effects of these agents in comparison with either placebo or other therapies. The researchers were unable to perform a meta-analysis of the data “due to considerable clinical heterogeneity among the studies” in design, patient populations, the drug formulations and dosages examined, the comparator treatments, and the outcomes measured.

Only seven randomized clinical trials were available for review. These had relatively small sample sizes and included only 449 patients in total. They assessed different drug formulations and different, short treatment durations ranging from 2.8 to 4 months. The overall quality of the evidence was rated “moderate.”

All randomized controlled trials reported statistically significant efficacy with fumaric acid ester treatment; mean Psoriasis Area Severity Index (PASI) scores decreased in 42%-65% of patients after 12-16 weeks of treatment. Adverse events were common, affecting 69%-92% of patients, and chiefly involved gastrointestinal complaints, flushing, and laboratory abnormalities such as elevated liver enzymes (up to 62%), eosinophilia (up to 46%), and lymphocytopenia (up to 38%). A total of 8%-39% of patients discontinued treatment because of adverse effects.

There also were 37 observational studies involving a total of 3,457 patients. Almost all were open-label, single-center, uncontrolled cohort studies or retrospective case series with small samples. Treatment duration ranged from 1 month to 14 years. The overall quality of the evidence was rated “very low” ( Br J Dermatol. 2016. doi: 10.1111/bjd.14500 ).

These studies reported similar outcomes to the randomized clinical trials: significant reductions in the extent and severity of psoriasis with fumarate treatment, and frequent adverse effects, predominantly GI problems, flushing, and laboratory abnormalities. Mean reductions in PASI were 13%-86% after 3-4 months of treatment. Several immunosuppressive adverse effects were linked to the treatment, including Kaposi’s sarcoma, organizing pneumonia, tuberculous lymphadenitis, squamous cell carcinoma, melanoma, and seven cases of progressive multifocal leukoencephalopathy. In addition, several renal complications were reported, including six cases of Fanconi syndrome and nine cases of acute renal insufficiency, and there was one case of collagenous colitis.

“Fumaric acid esters have a long history as a systemic psoriasis treatment” dating back to the 1950s, “but their development was not based on high-quality evidence,” Dr. Balak and his associates said.

They added that several randomized clinical trials assessing these agents are currently underway, but their findings haven’t yet been published. And new fumarates for the treatment of psoriasis currently are in development.

No sponsor or funding source was identified for this study. Dr. Balak and his associates reported having no relevant financial disclosures.