fumarates and Lymphopenia

Certain disease modifying therapies may negatively impact the humoral response to SARS-CoV-2 vaccines. Many MS related clinical, demographic, and immunological characteristics can also affect vaccine response but those have not been fully explored. This study aimed to investigate potential correlations between clinical, demographic, and immunological variables in MS patients to post-vaccination spike protein antibody positivity rates and levels.. Patients with MS and related neuroimmunological disorders who requested verification of the immune response to the SARS-COV-2 vaccine were tested for the spike protein antibody from January to October 2021. We performed an exploratory analysis to compare patients with positive versus negative spike protein antibody.. Fifty patients (mean age 53 ±12, 78% females) were included. There were 29 patients with positive post-vaccination spike protein antibody (58%) and 21 with negative antibody (42%). Patients with negative antibody were more likely to have been on B-cell therapy (86% vs 31%, P=.001) while positive patients were more likely to have been on a fumarate (31% vs 4.8%, P=.03). Thirty percent of positive patients on fumarate therapy had mild lymphopenia. No differences existed between groups in gender, age, race, disease phenotype, vaccine brand, and lymphocyte counts. Among patients on B-cell therapy, 33% had a positive spike protein antibody. There was an association between detectable CD19 cells at time of vaccination and positive humoral response to vaccination (P=0.049). There was no relationship between subgroups in terms of vaccine timing relative to B-cell therapy dose. Hypogammaglobulinemia was not associated with seroconversion rates, however it was associated with decreased quantitative spike protein antibody levels (p=0.045).. B-cell therapy is associated with a negative humoral response to SARS-COV-2 vaccines. Patients on B-cell depleting therapy with detectable CD19 counts at the time of vaccination were associated with a positive humoral response. There was no relationship between hypogammaglobinemia and seroconversion rate, however it was associated with decreased spike protein antibody levels. The fumarates are associated with positive humoral response even in the presence of mild lymphopenia.

Topics: Antibodies, Viral; COVID-19; COVID-19 Vaccines; Female; Fumarates; Humans; Lymphocyte Count; Lymphopenia; Male; Multiple Sclerosis; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccination

Fumaric acid esters (FAEs) have been used for fifty years to treat moderate-to-severe psoriasis. However, recent case reports of progressive multifocal leukoencephalopathy, associated with FAE-induced lymphopaenia, have been a cause for concern (J Dtsch Dermatol Ges. 2009;7:603).. We report six cases of persistent lymphopaenia following cessation of treatment with FAEs, with a mean duration of lymphopaenia of 33 months.. Given the lack of evidence regarding expected recovery of lymphocyte counts, further research is required to guide physicians in the risk stratification of patients prior to considering treatment with FAEs.

Topics: Aged; Female; Fumarates; Humans; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Psoriasis

Fumaric acid esters (FAEs) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects of FAEs on lymphocytes.. To evaluate the influence of long-term FAE (Fumaderm. In this single-centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiating FAE therapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping.. FAEs significantly reduced the numbers of CD4. Monitoring distinct T-cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both the FAE treatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoring CD4

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatologic Agents; Esters; Female; Fumarates; Humans; Immunophenotyping; Lymphopenia; Male; Middle Aged; Psoriasis; Retrospective Studies; T-Lymphocytes; Young Adult

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Fumarates; Humans; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Pharmacovigilance; Psoriasis; Retrospective Studies; Risk Assessment; Young Adult

Fumaric acid esters (FAEs) are a well-established efficacious systemic treatment for psoriasis. Recent recommendations from the European Medicines Agency suggest monitoring of full blood count every 4 weeks for the duration of therapy for psoriasis. The aim of our study was to assess the incidence of lymphopenia in patients taking FAEs and the impact of recent recommendations for our practice.. We reviewed 151 patients treated with FAEs for psoriasis between December 2013 and 2015.. Lymphopenia <700 × 109/L was detected within the last 12 months in 36/151 (24%) and lymphopenia <500 × 109/L in 10/151 (7%). Of 39 patients no longer on treatment, 7 (18%) stopped because of persistent lymphopenia.. The implementation of these recommendations would have significant resource implications and also likely influence the acceptability of FAEs to patients. Cessation of FAEs necessitates the need for alternative therapy, commonly biologic therapy.

Topics: Blood Cell Count; Drug Monitoring; Esters; Fumarates; Humans; Lymphopenia; Practice Guidelines as Topic; Psoriasis

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.. To examine the influence of FAEs on white blood cells with special regard to leukocytes, lymphocytes, and CD4+ and CD8+ cells during psoriasis therapy.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Follow-Up Studies; Fumarates; Humans; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Prospective Studies; Psoriasis; Young Adult

Topics: Dimethyl Fumarate; Fatal Outcome; Female; Fumarates; Humans; Immunosuppressive Agents; Leukocyte Count; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Lymphopenia; Middle Aged; Opportunistic Infections; Psoriasis

Topics: Delayed-Action Preparations; Dimethyl Fumarate; Fatal Outcome; Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphocyte Count; Lymphopenia; Middle Aged; Multiple Sclerosis; Opportunistic Infections

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphopenia

Topics: Female; Fumarates; Humans; Immunosuppressive Agents; Leukoencephalopathy, Progressive Multifocal; Lymphopenia

Fumaric acid esters (FAE) have been used to treat severe psoriasis in northern Europe for over 20 years. A recent systematic review has shown FAE to be an effective systemic treatment for severe psoriasis. However, FAE remain unlicensed in the U.K.. To present data relating to the efficacy and tolerability of FAE in severe psoriasis and report our experiences of FAE therapy at one U.K. centre.. Patients who had received FAE for severe psoriasis at one U.K. regional referral centre between June 1999 and October 2003 were identified from pharmacy records. Their records were analysed retrospectively.. Fifty-eight patients (25 women, 33 men) were identified. Fifty-five (95%) of the 58 patients had previously used other systemic antipsoriatic therapies with over 70% previously using two or more agents. Thirty-two patients (55%) showed improvement in their psoriasis with 10 (17%) being rated as 'clear' or 'virtually clear' by the attending physician. No improvement was seen in 28% patients and 16% showed worsening of their disease. Adverse events were common and were reported in 66% patients. These mainly consisted of abdominal pain (61%), diarrhoea (55%), flushing (45%), nausea (21%) and malaise (15%). They led to discontinuation of treatment in 15 patients after a mean period of 4.7 months. Lymphocytopenia developed during treatment in 57% of patients, all of whom had had a baseline value within the normal range. In only one patient was this considered severe enough to warrant withdrawal of treatment.. Our study has shown that FAE are an effective therapy in selected patients with severe psoriasis, even in those who have previously been intolerant of systemic therapy or where it has failed.

Topics: Adolescent; Adult; Aged; Chemical and Drug Induced Liver Injury; Chi-Square Distribution; Dimethyl Fumarate; Eosinophilia; Female; Fumarates; Humans; Immunosuppressive Agents; Liver; Liver Diseases; Lymphopenia; Male; Middle Aged; Psoriasis; Retrospective Studies; Treatment Outcome

Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow-up periods. In view of the chronic character of psoriasis, long-term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment.. To investigate adverse events of therapy with systemic FAE with follow-up periods of up to 14 years, in order to determine safety aspects of their long-term use in patients with severe psoriasis.. Current and/or past therapeutic use of FAE was reviewed in 66 patients with severe psoriasis.. Forty-one of 66 patients had received FAE for at least 1 year, and 12 of these 41 patients had received FAE for between 10 and 14 years. Adverse events were reported in 73% of the patients. These were usually mild and mainly consisting of flushing (55%), diarrhoea (42%), nausea (14%), tiredness (14%) and stomach complaints (12%). A relative lymphocytopenia was observed in 76% of patients during therapy with FAE, resulting in a permanent discontinuation of therapy with FAE in four patients. A transient eosinophilia and moderate liver enzyme elevations were observed in 14% and 25% of patients, respectively.. The present study indicates that FAE can be considered as a safe long-term treatment in patients with severe psoriasis.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Dermatologic Agents; Drug Administration Schedule; Female; Fumarates; Humans; Liver; Lymphopenia; Male; Middle Aged; Psoriasis