Lymphopenia and CD4+/CD8+ Cell Reduction under Fumaric Acid Esters

Abstract

Background: Fumaric acid esters (FAEs) are a broadly used therapy option for patients suffering from moderate-to-severe plaque psoriasis. Various studies in psoriasis have already shown peripheral blood lymphopenia during oral FAE therapy. Smaller studies also documented a reduction of CD4+ and CD8+ cell counts. Up to now, there are few case reports on opportunistic infections under FAE therapy - all of them associated with lymphopenia. Objective: To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy. Patients and Methods: A cohort of 105 patients with diagnosed moderate-to-severe chronic plaque psoriasis was enrolled in this single-centre observational trial. For a cohort of 36 patients, T-cell subset analyses were performed. Results: Of the total, 65 patients were male (61.9%) and 40 (38.1%) female; the mean age was 43.3 years (range 16-73 years). The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy. When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia. Severe lymphopenia (<500/µL) was documented in 11.4% of the patients. The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively. Conclusion: To the best of our knowledge this is the largest clinical investigation analysing prospectively CD4+ and CD8+ cell counts in psoriasis patients receiving FAEs. We suggest periodic monitoring of absolute lymphocyte counts as well as the establishment of the determination of T-cell subsets prior to and during therapy.

Long‐term real‐life safety profile and effectiveness of fumaric acid esters in psoriasis patients: a single‐centre, retrospective, observational study

“…49 Usually, these phenomena are transient and reversible 14,[50][51][52] and may serve as a biomarker for drug efficacy of FAEs. 53 The changes in leucocyte and lymphocyte counts observed in the present study (Table 7) compare well with those recently reported by Sondermann et al 54 In that study, which included a much smaller cohort of 105 patients with psoriasis, the median leucocyte count decreased by about 17.3% and the median lymphocyte count by about 35.8% in the first 6 months of FAE therapy. Over a maximum FAE treatment period of 112 months, that group observed severe lymphopenia (CTCAE grade 3 or 4) in 11.4% of patients.…”

“…Over a maximum FAE treatment period of 112 months, that group observed severe lymphopenia (CTCAE grade 3 or 4) in 11.4% of patients. Although severe, persistent leucopenia and lymphopenia events were rare, these AEs resulted relatively often in the physician's decision to discontinue treatment to decrease the risk of opportunistic infection . Although opportunistic infections are very rare, 19 cases of progressive multifocal leucoencephalopathy have been identified among patients treated with different FAE preparations to date; 14 of these occurred during therapy for psoriasis (11 patients used Fumaderm ® and three patients used Psorinovo ® , DMF, compounding pharmacy).…”

“…All of these patients were lymphopenic and had been receiving FAE therapy for prolonged periods. Only patients with prolonged uncontrolled lymphopenia during FAE therapy seem to be at higher risk for this very rare but serious side‐effect of FAEs . Additionally, fatal cases of West Nile encephalitis, generalized varicella zoster, and Kaposi sarcoma have been associated with FAEs .…”

“…Although severe, persistent leucopenia and lymphopenia events were rare, 49,55 these AEs resulted relatively often in the physician's decision to discontinue treatment to decrease the risk of opportunistic infection. 54 Although opportunistic infections are very rare, 19 cases of progressive multifocal leucoencephalopathy have been identified among patients treated with different FAE preparations to date; 56,57 14 of these Long-term real-life use of FAEs in psoriasis occurred during therapy for psoriasis (11 patients used Fumaderm â and three patients used Psorinovo â , DMF, compounding pharmacy). All of these patients were lymphopenic and had been receiving FAE therapy for prolonged periods.…”

“…Only patients with prolonged uncontrolled lymphopenia during FAE therapy seem to be at higher risk for this very rare but serious side-effect of FAEs. 7,54 Additionally, fatal cases of West Nile encephalitis, 58 generalized varicella zoster, 59 and Kaposi sarcoma 60 have been associated with FAEs. 61 In our total cohort, we did not observe any severe or opportunistic infections leading to treatment discontinuation.…”