Patients with atopic dermatitis with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Roekevisch, Evelien; Leeflang, Mariska; Schram, M. E.; Campbell, Linda E.; McLean, William; Kežić, Sanja; Bos, Jan D.; Spuls, Phyllis I.; Middelkamp‐Hup, Maritza A.

doi:10.1111/bjd.15191

Cited by 14 publications

(11 citation statements)

References 4 publications

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“…Previously, we showed a better response of systemic treatment in the non-FMG group over the course of 24 weeks. 3 However, in this study, we observe that this difference in effect fades away over time, and after 2 years the response in both groups is comparable. In the non-FMG group, there is a steep curve in reduction in SCORAD index in the first 3 months; in other words, not much further improvement is to be expected after 3 months of therapy (absolute SCORAD index reduction of only 4 points), whereas in the FMG group significant effect can still be expected (absolute SCORAD index reduction of 25 points).…”

contrasting

confidence: 52%

Methotrexate versus azathioprine in patients with atopic dermatitis: 2-year follow-up data

Roekevisch

Schram

Leeflang

et al. 2018

Journal of Allergy and Clinical Immunology

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Long-term data of methotrexate (MTX) and azathioprine (AZA) in atopic dermatitis (AD) are lacking. Previously, we published the results of a randomized controlled trial of 42 adults with severe AD treated with MTX or AZA for 12 to 24 weeks. Both MTX and AZA induced significant reductions in SCORing Atopic Dermatitis (SCORAD) index at 12 and 24 weeks after baseline, without a significant difference between treatments. 1 To assess long-term efficacy and safety of MTX versus AZA, all 42 patients were asked to participate in an observational follow-up study to be evaluated 3 monthly for 2 years. After 12 weeks of treatment with MTX or AZA, treatments were continued, stopped, or switched, reflecting normal clinical practice. The same outcomes as in the original randomized controlled trial were investigated, which correspond to the 4 core outcome domains for AD suggested by the Harmonising Outcome Measures for Eczema initiative. Patients were scored by trained blinded investigators. One of the primary outcomes was the difference in mean absolute and relative change in SCORAD

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contrasting

confidence: 52%

Methotrexate versus azathioprine in patients with atopic dermatitis: 2-year follow-up data

Roekevisch

Schram

Leeflang

et al. 2018

Journal of Allergy and Clinical Immunology

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“…Seven studies analyzed the association between FLG mutations and eczema severity [48,50,53,71,87,88,90]. Chang et al found that FLG LoF homozygotes and heterozygotes were less likely to report periods of skin clearance (OR 0.20; 95% CI 0.07-0.55) and more likely to report frequent steroid use (OR 3.18; 95% CI 1.22-8.30) [71].…”

Section: Filaggrin Mutations and Eczema Severitymentioning

confidence: 99%

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review

Martı́n

Estravís

Garcı́a-Sánchez

et al. 2020

Genes

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Background: Atopic dermatitis is a common inflammatory skin disorder that affects up to 15–20% of the population and is characterized by recurrent eczematous lesions with intense itching. As a heterogeneous disease, multiple factors have been suggested to explain the nature of atopic dermatitis (AD), and its high prevalence makes it necessary to periodically compile and update the new information available. In this systematic review, the focus is set at the genetic and epigenetic studies carried out in the last years. Methods: A systematic literature review was conducted in three scientific publication databases (PubMed, Cochrane Library, and Scopus). The search was restricted to publications indexed from July 2016 to December 2019, and keywords related to atopic dermatitis genetics and epigenetics were used. Results: A total of 73 original papers met the inclusion criteria established, including 9 epigenetic studies. A total of 62 genes and 5 intergenic regions were described as associated with AD. Conclusion: Filaggrin (FLG) polymorphisms are confirmed as key genetic determinants for AD development, but also epigenetic regulation and other genes with functions mainly related to the immune system and extracellular matrix, reinforcing the notion of skin homeostasis breakage in AD.

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“…Thymus and activation-regulated chemokine (TARC) was suggested to be the single best biomarker to assess disease severity [4], panels of biomarkers were proposed as “objective” substitutes for the EASI [5] and SCORAD [6] severity scores, and a discovery of AD endotypes was attempted by clustering of biomarker measurements [7]. Furthermore, the presence of FLG mutations [9] [10] and a high level of serum IgE [11] were found to be associated with poor treatment outcome for AD. However, biomarkers to predict therapeutic responses has been less studied for AD [8].…”

Section: Introductionmentioning

confidence: 99%

Can serum biomarkers predict the outcome of systemic therapy for atopic dermatitis?

Hurault

Roekevisch

Schram

et al. 2020

Preprint

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SUMMARYBackgroundAtopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification, rather than the “one-size-fits-all” treatments, is of high clinical relevance. It has been hypothesised that the measurement of biomarkers could help predict therapeutic response for individual patients.ObjectiveWe aim to assess whether biomarkers can predict the outcome of systemic therapy.MethodsWe developed a statistical machine learning predictive model using the data of an already published longitudinal study of 42 patients who received systemic therapy. The data contained 26 serum cytokines measured before the therapy. The model described the dynamics of the latent disease severity and measurement errors to predict AD severity scores (EASI, (o)SCORAD and POEM) two-weeks ahead. We conducted feature selection to identify the most important biomarkers for predicting the AD severity scores.ResultsWe validated our model and confirmed that it outperformed standard time-series forecasting models. Adding biomarkers did not improve predictive performance. Our estimates of the minimum detectable change for the AD severity scores were larger than already published estimates of the minimal clinically important difference.ConclusionsBiomarkers had a negligible and non-significant effect for predicting the future AD severity scores and the outcome of the systemic therapy. Instead, a historical record of severity scores provides rich and insightful dynamical information required for prediction of therapeutic responses.

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Patients with atopic dermatitis with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Cited by 14 publications

References 4 publications

Methotrexate versus azathioprine in patients with atopic dermatitis: 2-year follow-up data

Methotrexate versus azathioprine in patients with atopic dermatitis: 2-year follow-up data

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review

Can serum biomarkers predict the outcome of systemic therapy for atopic dermatitis?

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