Use Of Dimethyl Fumarate Research Articles

Use of dimethyl fumarate for MS not linked to Fanconi syndrome

Use of dimethyl fumarate for MS not linked to Fanconi syndrome

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

Divulging the Intricacies of Crosstalk Between NF-kB and Nrf-2/Keap1 Pathway in the Treatment of Arthritis by Dimethyl Fumarate.

The aim of this study was to examine the hypothesis that use of dimethyl fumarate (DMF) may mitigate arthritic symptoms in collagen-induced arthritis (CIA) rats through activation of NF-E2-related factor 2(Nrf-2) and suppression of NF-kB pathway. Arthritis in rats was induced by subcutaneous injection of collagen type II (200µl) at the base of the tail. After inductionarthritic rats were treated with DMF (25mg/kg b.wt.) for 20daysfrom the day 25th to 45th. At the end of the study, serum and joint homogenate was used to assess the oxidative stress and cytokines level. In addition, mRNA expression of various genes such as NF-kB,Keap-1 (Kelch-like ECH-associated protein 1) and Nrf-2 was assayed through qRT-PCR in joint tissue. Finally, all these biochemical and molecular results were confirmed by histological and in silico study. Our results showed that decrease in the clinical severity, inflammation, and cell necrosis in DMF-treated rats. This was related with decrease in NF-kB activity and increase in activity of Nrf-2. Treatment with DMF increases the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and decreases inflammation. These biochemical and molecular results were further confirmed by performing in silico study that shows DMF strongly inhibits the activation of NF-kB, and conversely at the same time increases the activity of Nrf-2 that means a significantly lower amount of inflammatory mediators and oxidants was produced. Decrease in inflammation leads to preserving the joint architecture and alleviation from clinical symptoms of arthritis. Collectively, these results indicate that Nrf-2 activation protects against arthritic symptoms.

Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune‐driven demyelination

AbstractObjectivesMultiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease‐modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.MethodsUsing the well‐established murine model for immune‐driven demyelination of MS, experimental autoimmune encephalomyelitis, the effect of KOR agonists in combination with DMTs fingolimod or dimethyl fumarate on disease progression, immune cell infiltration and activation as well as myelination were analysed.ResultsFingolimod in combination with the KOR agonist, nalfurafine, significantly increased each individual beneficial effect as measured by increased recovery of mice and reduced relapses. These beneficial effects correlated with a reduction in immune cell infiltration into the CNS as well as peripheral immune cell alterations including a reduction in autoreactive CD4+ T‐cell cytokine production as well as increased myelination in the spinal cords of co‐treated animals. In contrast, while the use of dimethyl fumarate in combination with nalfurafine did not adversely affect the benefits of nalfurafine, the combination did not significantly enhance those benefits.ConclusionThis study indicates that KOR agonists can be used in combination with fingolimod and dimethyl fumarate with the nalfurafine–fingolimod combination providing enhanced benefits.

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method.

Dimethyl fumarate (DMF) is a widely used oral disease-modifying therapy for multiple sclerosis (MS). Its efficacy and safety profiles are supported by over a decade of experience. Differences exist between Asia and Europe/United States in the prevalence and characteristics of MS; most data for DMF are derived from populations outside Asia. DMF was recently (2021) approved for use in China. The objectives of this review were to evaluate the evidence for DMF's profile, to provide an update to healthcare providers on current knowledge surrounding its use and to assess the relevance of existing data to use in China. This study used a modified Delphi method based on the insights of a scientific Steering Committee (SC), with a structured literature review conducted to assess the data of DMF. The literature review covered all papers in English (from 01 January 2011 to 21 February 2022) that include 'dimethyl fumarate' and 'multiple sclerosis', and their MeSH terms, on PubMed, supplemented by EMBASE and Citeline searches. Papers were categorized by topic and assessed for relevance and quality, before being used to formulate statements summarizing the literature on each subject. SC members voted on/revised statements, requiring ⩾80% agreement and ⩽10% disagreement for inclusion. Statements not reaching this level were discussed further until agreement was reached or until there was agreement to remove the statement. A total of 1030 papers were retrieved and used to formulate the statements and evidence summaries considered by the SC members. A total of 45 statements were agreed by the SC members. The findings support the positive efficacy and safety profile of DMF in treating patients with MS. Limited Chinese patient data are an ongoing consideration; however, based on current evidence, the statements are considered applicable to both the global and Chinese populations. DMF is a valuable addition to address unmet MS treatment needs in China. Registration: Not applicable.

Real-world use of dimethyl fumarate in patients with plaque psoriasis: a Delphi-based expert consensus.

Dimethyl fumarate (DMF) was recently approved by the European Medicines Agency for systemic treatment of moderateto- severe chronic plaque psoriasis. Appropriate management of DMF treatment is required to achieve optimal clinical benefits. 7 dermatology experts gathered online for 3 meetings to identify consensus on the use of DMF in patient selection, drug dosage/titration, side effects management, and follow-up, with the aim to provide guidance on the use of DMF for psoriasis in clinical dermatological practice based on literature data and expert opinion. 20 statements were discussed and voted on using a facilitator- mediated modified Delphi methodology. Strong consensus was reached for all statements (agreement level of 100%). DMF treatment is characterized by dosage flexibility, sustained efficacy, high rates of drug survival, and low potential for drug-drug interactions. It can be used in a broad range of patients, including the elderly or those with comorbidities. Side effects (mainly gastrointestinal disorders, flushing, and lymphopenia) are frequently reported but are generally mild and transient and can be minimized by dosage adjustments and a slow titration schedule. Hematologic monitoring throughout the treatment course is required to reduce the risk of lymphopenia. This consensus document provides clinical dermatologists with answers on the optimal use of DMF to treat psoriasis.

Diroximel Fumarate as a Novel Oral Immunomodulating Therapy for Relapsing Forms of Multiple Sclerosis: A Review on the Emerging Data.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation oral fumaric acid ester (FAE) that was developed as a formulation with better GI tolerability. The improved tolerability is assumed to be related to a lower synthesis of gut-irritating methanol. Other explanations for DRF's lower extent of GI irritation include a more modest off-target activity due to its chemical structure. The superior GI tolerability of DRF compared to DMF could be proven in clinical trials and lead to approval of DRF for the treatment of relapsing forms of MS/relapsing-remitting MS (United States Food and Drug Administration and European Medicines Agency, respectively). Here, we summarize the mode of action of oral FAE and compare the chemical and physiological characteristics of DMF and DRF. Moreover, we discuss the adverse effects of FAE and introduce the emerging preclinical and trial data leading to the approval of DRF in MS. This article additionally reviews our current understanding of coronavirus disease 2019 (COVID-19) and the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in people treated with FAE.

Effects of Scale-Up and Impeller Types on Spherical Agglomeration of Dimethyl Fumarate

Spherical agglomeration (SA) allows for intensifying a crystallization process through simultaneous particle size enlargement and process efficiency enhancement, without a compromise between bioavailability and processability of active pharmaceutical ingredients (APIs). Inefficient collision intensity may encounter during scale-up of an SA process, while mixing intensity and flow patterns do play critical roles especially in a batchwise stirred tank. In the present study, the scalability of an SA process by operating at all the same configurations of different scales, 0.5, 2, and 10 L, using a common one-layered impeller with four pitched blades was examined through the use of dimethyl fumarate as a model API. Insights into the guidelines for scaling up of the SA process are also given. Furthermore, the effects of impeller types, including the one-layered impeller, the two-layered impeller with four pitched blades, and the maxblend impeller, on the size, size distribution, and roundness of dimethyl fumarate agglomerates were investigated carefully.

Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis.

To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses. We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

Proposed Neuroimmune Roles of Dimethyl Fumarate, Bupropion, S-Adenosylmethionine, and Vitamin D3 in Affording a Chronically Ill Patient Sustained Relief from Inflammation and Major Depression.

We had discussed earlier that, after most of the primary author’s multiple sclerosis (MS) symptoms were lessened by prior neuroimmune therapies, use of dimethyl fumarate (DMF) gradually subdued his asthma and urticaria symptoms, as well as his MS-related intercostal cramping; and bupropion supplemented with S-adenosylmethionine (SAMe) and vitamin D3 (vit-D3) helped remit major depression (MD). Furthermore, the same cocktail (bupropion plus supplements), along with previously discussed routines (yoga, meditation, physical exercises, and timely use of medications for other illnesses), continued to subdue MD during new difficulties with craniopharyngioma, which caused bitemporal vision loss; sphenoid sinus infections, which caused cranial nerve-VI (CN6) palsy and diplopia; and through their treatments. Impressed with the benefit the four compounds provided, in this manuscript, we focus on explaining current neuroimmune literature proposals on how: (1) DMF impedes inflammation, oxidative stress, and cell death in CNS and peripheral tissues; (2) Bupropion curbs anxiety, MD, and enhances alertness, libido, and moods; (3) SAMe silences oxidative stress and depression by multiple mechanisms; and (4) Vit-D3 helps brain development and functioning and subdues inflammation. We realize that herein we have reviewed proposed mechanisms of remedies we discovered by literature searches and physician assisted auto-experimentation; and our methods might not work with other patients. We present our experiences so readers are heartened to reflect upon their own observations in peer-reviewed forums and make available a wide body of information for the chronically ill and their physicians to benefit from.

Exploring the Use of Dimethyl Fumarate as Microglia Modulator for Neurodegenerative Diseases Treatment

The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression.

Prevalence of Latent Tuberculosis in the Multiple Sclerosis Clinic and Effect of Multiple Sclerosis Treatment on Tuberculosis Testing.

Patients with a compromised immune system are at risk for converting from latent tuberculosis infection (LTBI) to active tuberculosis (TB) infection. Multiple sclerosis (MS) therapies may put individuals with LTBI at higher risk of TB. Patients at the Beth Israel Deaconess Medical Center MS Clinic were screened for TB as part of routine testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay (Cellestis Ltd) from 2013 to 2017. Patients were tested either before or during immunomodulatory therapy. Four of 222 patients (1.8%; 95% CI, 0.1%-3.6%) had positive QFT-GIT results; three patients had risk factors for TB, having emigrated from TB-endemic countries or worked in the health care industry. Twenty-eight of 222 patients (12.6%) had an indeterminate assay result, and 75.0% of these occurred in patients taking dimethyl fumarate. Fingolimod, natalizumab, or anti-CD20 treatments showed 0% to 7.7% indeterminate results. The prevalence of LTBI was 1.8% in the Beth Israel Deaconess Medical Center MS Clinic. Not all LTBI cases were associated with known risk factors for TB. Screening for LTBI before starting immunosuppressive agents for MS could help prevent activation of TB. Dimethyl fumarate use is associated with indeterminate QFT-GIT results, possibly due to functional effects on lymphocytes and levels of cytokines, such as interferon gamma. In contrast, fingolimod use was rarely associated with indeterminate QFT-GIT results despite a high rate of lymphopenia in virtually all patients.

Assessing Barriers to Adherence with the Use of Dimethyl Fumarate in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, central nervous system demyelinating disease that requires long-term use of disease-modifying therapies (DMT). Patient adherence to DMT is key in reducing the inflammation that leads to relapses and neurodegeneration. Dimethyl fumarate (DMF) poses unique challenges to adherence including being the only twice-daily dosing DMT. Previous research suggests there are direct roles that providers play on improving their patients' adherence rates, such as focusing on the patient-provider relationship, helping put the patient at ease so that they feel understood and respected. Also, route of administration affects adherence in other chronic healthcare conditions. However, the issue of adherence to DMT in MS is more complex than just route of administration, with adverse effects being the main predictor of adherence. (1) To define various patient specific factors (e.g. fatigue and mood disorders) that affect adherence with DMF and (2) to understand how patients' perceptions of treatment satisfaction (such as effectiveness, convenience, side effects and global satisfaction) and DMFs impact on quality of life (such as social support, activities of daily living, coping) influence adherence. Our study was a prospective, observational measurement of adherence to treatment with DMF in MS patients over 52weeks. Twenty-five out of thirty-five patients enrolled completed the study. Adverse event (AE) data was reviewed on all participants. Adherence rates correlated with patient's perceived effectiveness (0.25, p < 0.023) and the level of bothersome symptoms the patient experienced (0.45, p < 0.0001). The majority of new AE onset was reported within 12weeks of DMF initiation. This is consistent with previously published data with DMF use. Adherence rates are an important factor to be considered when starting patients on DMT. DMF creates its own barriers to adherence with our study highlighting some, including twice-daily dosing and AEs experienced following treatment initiation. Healthcare providers should be aware of these barriers prior to treatment initiation and counsel patients appropriately.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BackgroundCurrent data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing–remitting multiple sclerosis (RRMS) is limited.ObjectivesTo assess the efficacy of DMF in Japanese patients with RRMS.MethodsThe phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12–24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase.ResultsDMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12–24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks.ConclusionsDMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

BackgroundThe use of dimethyl fumarate has not been reported in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis.ObjectivesThe purpose of this study was to evaluate the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis.MethodsAPEX was a phase 3, multinational trial, which consisted of a 24-week, randomized (1:1), double-blind study where patients received dimethyl fumarate 240 mg or placebo twice daily, followed by an open-label extension where all patients received dimethyl fumarate 240 mg. The primary endpoints were the total number of new gadolinium-enhancing (Gd+) lesions in Weeks 12–24 (Part I) and long-term safety (Part II). This post-hoc subgroup analysis evaluated the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis (n=52) up to Week 72 (24 weeks Part I and 48 weeks Part II).ResultsDimethyl fumarate reduced the mean total number of new gadolinium-enhancing lesions at Weeks 12–24 by 94% versus placebo; the number of patients who had a relapse over 24 weeks was reduced by 72%. Adverse events leading to discontinuation of the study drug were reported in 9% of patients receiving placebo/dimethyl fumarate and 4% of patients in dimethyl fumarate/dimethyl fumarate.ConclusionsDimethyl fumarate demonstrated sustained efficacy and acceptable tolerability in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis for 72 weeks.

Clinical guidelines for the use of dimethyl fumarate in relapsing-remitting multiple sclerosis

Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease. The new oral agent for the treatment of relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (DMF), helps change the pathogenetic mechanisms of the disease, thus decreasing the rate of exacerbations, slowing down disease progression, and reducing the risk of radiological progression of the disease.

Factors associated with dimethyl fumarate use and treatment patterns among patients with multiple sclerosis in a real-world setting

Factors associated with dimethyl fumarate use and treatment patterns among patients with multiple sclerosis in a real-world setting

The effectiveness of dimethyl fumarate monotherapy in the treatment of relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

Background:Dimethyl fumarate (BG-12, Tecfidera®) is a new oral drug approved by FDA and EMA in March 2013 for relapsing – remitting multiple sclerosis (RRMS). The drug was much anticipated because of its possible superiority over currently available medications: fingolimod and teriflunomide as the only MS treatments currently available in oral form.Objective:The aim of this systematic review with meta-analysis was to assess the efficacy and safety of BG-12 in the treatment of RRMS.Methods:A systematic literature search was conducted in Medline/PubMed, EMBASE, and Cochrane Library up till 3rd November, 2013. We sought all published randomized clinical trials evaluating the use of dimethyl fumarate for the treatment of patients with RRMS. All included studies were critically appraised and analyzed with the use of Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol.Results:Two trials, DEFINE and CONFIRM involved 2 651 patients and compared dimethyl fumarate taken either two or three times daily with placebo in patients with RRMS. Additionally in CONFIRM trial third group of patients received glatiramer acetate. The overall results of the meta-analysis showed that BG-12 (at both dosages) given to patients with RRMS is safe and statistically significantly more effective than placebo in reducing the proportion of patients who had a relapse by 2 years, the rate of disability progression and the mean number of gadolinium-enhancing lesions at 2 years. The comparison between BG-12 and glatiramer acetate revealed that the analyzed agent could potentially be more effective in the treatment of RRMS.Conclusions:Despite limited RCTs data available, both analyzed BG-12 regimens showed their efficacy on clinical disease parameters and other measures of disease activity in RRMS. The safety profile of the study agent was acceptable.

Dimethyl Fumarate (Tecfidera)

To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS). A comprehensive PubMed search was conducted in July 2013 using the search terms dimethyl fumarate and Tecfidera. Reference lists of abstracted publications were reviewed to identify relevant works that were not retrieved via the electronic search. Additional information was obtained from the FDA Web site, manufacturer prescribing information, and Clinicaltrials.gov. Clinical trials and review articles that included the use of dimethyl fumarate in the treatment of MS and were available in English were abstracted for review. The safety and efficacy of dimethyl fumarate for the treatment of relapsing remitting MS was confirmed in 2 phase III trials, DEFINE and CONFIRM. Relative to placebo, twice-daily dimethyl fumarate was found to reduce the proportion of patients with relapses at 2 years by 34% to 49% and the annualized relapse rate by 44% to 53%. Although the incidence of serious adverse effects did not differ from that of placebo, intolerable flushing and gastrointestinal adverse effects prompted discontinuation in 3% and 4% of patients, respectively. In March 2013, dimethyl fumarate was approved as a third oral option for patients with relapsing forms of MS. Although no head-to-head trials have been conducted, a comparison of data from phase III trials suggests that the efficacy of dimethyl fumarate is comparable to that of existing oral agents and may offer a preferable safety profile.

Survey of Dimethyl Fumarate in Desiccant Products During 2009 in Italy

Dimethyl fumarate (DMFu) is a substance with remarkable hygroscopicity and fungicidal power, which has recently showed to be a strong sensitizer to humans. The use of DMFu in little desiccant pouches, for e.g. in handbags or footwear boxes, might result in the contamination of leather products, with the subsequent exposure to consumers by contact. In 2009, 153 samples of desiccant material were collected from leather manufactures all over Italy and analyzed for DMFu. Results proved to fall in a wide range (0.14-7145mg/kg).