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Introduction to dermatological treatment
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
There are no reports of severe long-term toxicity, development of cancers or a higher susceptibility to bacterial infections. This makes fumaric acid esters a safe regimen, compared to other agents. Dosing starts at 30 mg daily increasing weekly to a maximum of 240 mg t.i.d.
Clinical applications of magnesium in cutaneous medicine
Published in Kupetsky A. Erine, Magnesium, 2019
Laura Marie Jordan, Sunny K. Chun
Moderate success has also been seen in the treatment of psoriasis with fumaric acid esters (FAEs) due to their immunomodulatory and anti-inflammatory effects. Specifically, Ghoreschi et al. found that fumarate treatment in humans interferes with the production of IL-12 and IL-23, which promote pathogenic Th-cell differentiation.26 Psoriasis is approved to be treated with Fumaderm in Germany, an FAE containing dimethylfumarate, calcium, magnesium, and zinc salts of monoet hyl hydrogen fumarate. Atwan et al.’s review of literature included six randomized controlled trials studying the FAE treatment of psoriasis and found that FAEs are more efficacious than placebo treatment and potentially equitable to methotrexate for psoriasis. However, the authors acknowledge limitations to their study, as four out of the six studies were either abstracts or reports.27
Current Recommendations for the Treatment of Psoriasis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
FP187 (Forward-Pharma) is a dimethyl fumarate currently undergoing phase III clinical trials for its treatment in both psoriasis and multiple sclerosis. Data from phase II clinical studies have not yet been published. Fumaric acid esters have been used to treat psoriasis for decades in northern Europe but are not yet available in the United States. Its mechanism is not entirely understood, but one commonly proposed theory involves decreased translocation of NF-kB, leading to the decreased expression of pro-inflammatory cytokines.76,77 Progressive multifocal leukoencephalopathy has been reported in case reports of patients who received long-term fumaric acid therapy.78,79
Development of applicable thiol-linked antibody–drug conjugates with improved stability and therapeutic index
Published in Drug Delivery, 2022
Yanming Wang, Fei Xie, Lianqi Liu, Xin Xu, Shiyong Fan, Wu Zhong, Xinbo Zhou
To develop a novel type of thiol-linked linker system, we designed a variety of thiol-reactive maleimide analogs based on maleic acid amide, fumaric acid amide, fumaramide methyl ester, and maleamic methyl ester groups in order to develop a novel type of thiol-linked linker system for ADCs. Initially, we synthesized two linker-MMAE conjugates (S5 and S6) with a thiol-reactive maleic acid amide (Supporting Information, Scheme S1). During the preparation of the corresponding ADCs, we found that even if the reaction time was extended by 10-fold, only a very small amount (DAR <0.5) of antibody modification could be achieved (Supporting Information, Figure S1). Moreover, we tried to react fumaric acid amide with the reduced antibody, but the desired effect was also not achieved (data not shown). We speculate that the hydrolysis of the maleimide ring to maleic acid changed the ring tension in the original structure. In addition, the generated carboxyl group may significantly reduce the electron cloud density of the double bond or form a hydrogen bond with the thiol (Knight, 1979; Ryan et al., 2011), which is not conducive to the reaction with the thiol groups of the antibody.
Multiarm study comparing patient-reported and clinical outcome measures in patients undergoing antipsoriatic therapy with non-biological systemic agents in a real-world setting
Published in Journal of Dermatological Treatment, 2022
Christine Fink, Christina Alt, Timo E. Schank, Katharina Sies, Samuel Kilian, Knut Schäkel
Overall, 28 out of 80 (35.0%) patients interrupted antipsoriatic therapy during the first 6 months. Therapy interruption rate was considerably higher in patients receiving fumaric acids (64.3%) compared to apremilast (22.2%) and methotrexate (16.0%; p = 0.001). Antipsoriatic therapy was interrupted by 3 of the 6 patients (50.0%) in the apremilast group due to secondary drug failure, one patient (16.7%) discontinued due to side-effects (recurrent severe headache), another patient (16.7%) due to therapy inefficacy and one patient (16.7%) was lost to follow-up. In the methotrexate group 2 (50.0%) of the total 4 therapy-interrupting patients suffered from side effects (gastrointestinal AEs, i.e. diarrhea, nausea, and vomiting), one (25.0%) discontinued due to secondary drug failure and another patient (25.0%) was lost to follow-up. From the 18 patients interrupting therapy with fumaric acid 11 patients (61.1%) discontinued due to side effects (6 patients with gastrointestinal AEs i.e. diarrhea, nausea, and vomiting; 4 patients with severe lymphopenia, one patient with flush), 4 patients (22.2%) were lost to follow up and 3 patients (16.7%) interrupted due to therapy inefficacy. All study AEs were mild to moderate in severity. No serious AEs occurred within this study. In total, systemic therapy was discontinued after a mean period of 84.8 d (±54.7). Apremilast was administered for a mean period of 124.5 (±51.4) d until interruption compared to 75.0 (±67. 9) d in the methotrexate and 73.7 (±49.6) d in the fumaric acids group (p = 0.171) (Table 3).
Perspectives on the pharmacological management of psoriasis in pediatric and adolescent patients
Published in Expert Review of Clinical Pharmacology, 2021
Emmanuel Mahé, Maud Amy De La Bretêque, Céline Phan
Fumaric acid esters are licensed for use in pediatric patients in some countries. They are known to have immunomodulatory effects, but their mechanisms of action are unclear. The major disadvantage of fumaric acid esters is the length of time needed for these treatments to become effective: it may take 6 months or longer before their maximum effectiveness is observed. The effectiveness of fumaric acid esters in pediatric psoriasis has been evaluated in one retrospective study involving children with recalcitrant plaque psoriasis. The treatment reduces disease severity and improve quality of life in the majority of the children. Adverse events – gastrointestinal complaints (93%) and flushes (71%) – occurred frequently but were usually mild and transient [53]. Efficacy and efficiency can be improved by combining fumaric acid ester treatment with phototherapy [54].