The long‐term safety of topical corticosteroids in atopic dermatitis: A systematic review
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SUBMITTER: Harvey J
PROVIDER: S-EPMC10549798 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe use of oral corticosteroids for prolonged periods may be associated with adverse events (AEs). Nevertheless, the risk of AEs with oral corticosteroids, especially among patients with atopic dermatitis (AD), has not been comprehensively investigated and lacks evidence on duration of treatment.ObjectiveTo assess the association between long-term exposure to oral corticosteroids and AEs among adult patients with AD.Design, setting, and participantsThis nested case-control study used data from the Health Insurance Review and Assessment Service database of South Korea between January 1, 2012, and October 31, 2021, which included 1 year prior to the cohort entry date of January 1, 2013, for assessing exclusion criteria and baseline characteristics, and 1 year after the study end date of October 31, 2020, to ensure a minimum duration for assessing exposure. Among the population of adults with AD, patients diagnosed with any of 11 AEs were matched with patients who had never received a diagnosis of any of the 11 AEs.ExposureLong-term use of oral corticosteroids was defined as cumulative supply of more than 30 days or more than 90 days of oral corticosteroid prescription per year.Main outcomes and measuresWe used multivariable conditional logistic regression analyses to measure the risk of 11 individual outcomes (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) as the composite outcome, controlling for potential confounders. We further classified the composite outcome to individual outcomes to evaluate the AE-specific risk.ResultsAmong 1 025 270 patients with AD between 2013 and 2020, 164 809 cases (mean [SD] age, 39.4 [14.8]; 56.9% women) were matched with 328 303 controls (mean [SD] age, 39.3 [14.7]; 56.9% women) for sex, age, cohort entry date, follow-up duration, and severity of AD, where the balance of most baseline characteristics was achieved. A total of 5533 cases (3.4%) and 10 561 controls (3.2%) were exposed to oral corticosteroids for more than 30 days, while 684 cases (0.4%) and 1153 controls (0.4%) were exposed to oral corticosteroids for more than 90 days. Overall, there was no increased risk of AEs with use of oral corticosteroids for more than 30 days (adjusted odds ratio [AOR], 1.00; 95% CI, 0.97-1.04), whereas the risk was slightly higher with use of oral corticosteroids for more than 90 days (AOR, 1.11; 95% CI, 1.01-1.23). The small elevation in experiencing an AE was observed with each cumulative or consecutive year of ever long-term use.Conclusions and relevanceThis case-control study found a slightly increased risk of AEs associated with use of oral corticosteroids for more than 90 days per year, which warrants future research to fully elucidate the observed findings.
| S-EPMC11259904 | biostudies-literature
Project description:ProblemTo determine the safety and efficacy of topical corticosteroid versus vehicle/moisturizer in children under 2 years old (<2 y).Eligibility criteriaA systematic review and meta-analysis searching PubMed MEDLINE, Embase, Web of Science, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, NHS Economic Evaluation, CINAHL, GREAT, and Clinicaltrials.gov. We selected randomized controlled trials (RCTs) comparing topical corticosteroids to vehicle/moisturizer and included children <2 y. Two authors extracted data.SampleOnly one study limited analyses to children <2 y, so our review included participants older than 2 years. Twelve RCTs were included with 2224 participants. Ten studies were industry-sponsored.ResultsThe proportion of responders to topical corticosteroid across studies was 0.65 (95% CI, 0.54-0.74), as compared to vehicle/moisturizer 0.32 (95% confidence interval (CI), 0.20-0.48). The proportion of adverse events were similar between groups (topical steroids 0.17 (95% CI, 0.08-0.33) vs. vehicle/moisturizer 0.12 (CI 0.02-0.42)). High heterogeneity in treatment response occurred across studies that could not be explained by potential moderators. Mild adrenal suppression occurred in 4 of 157 measured participants (3%) receiving topical corticosteroids. Limitations include the few RCTs on this topic, the inclusion of participants >2 y and outcome measures and reporting methods rarely met CONSORT guidelines.ConclusionsTopical corticosteroids trended to being more effective and equally safe to vehicle/moisturizers, but generalizability is limited given the dearth of well-designed studies focused on children <2 y. Adverse events from vehicle/moisturizer may be greater than topical corticosteroid due to under treatment.ImplicationsFurther work is needed in this age group.
| S-EPMC7444023 | biostudies-literature
Project description:ObjectiveAn umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.MethodsEmbase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool).Results38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2-4 weeks).Key findingsTCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased.TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares ('weekend therapy') versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).ConclusionsW e found no evidence of harm when TCS were used intermittently 'as required' to treat flares or 'weekend therapy' to prevent flares. However, long-term safety data were limited.Prospero registration numberCRD42018079409.
| S-EPMC8264889 | biostudies-literature
Project description:Previous studies demonstrated that delgocitinib ointment, a novel topical Janus kinase inhibitor, rapidly improved clinical signs and symptoms of atopic dermatitis (AD) in Japanese adult patients. We sought to evaluate the long-term safety and efficacy of delgocitinib 0.5% ointment in a 52-week study (QBA4-2). Japanese patients aged 16 years or older with AD received delgocitinib 0.5% ointment b.i.d. for up to 52 weeks. Topical corticosteroids for the treatment of worsening of AD could be used at the investigators' discretion during the treatment period. Safety end-points included the incidence and severity of adverse events (AEs). Pooled safety analyses included the data from the other long-term study (QBA4-1). Efficacy end-points included the percentage change from baseline in the modified Eczema Area and Severity Index (mEASI). A total of 506 patients were included in the pooled safety population. Overall, AEs were reported in 69.0% of patients; most AEs were mild and unrelated to delgocitinib ointment. The most common AE was nasopharyngitis, followed by contact dermatitis, acne, and application site folliculitis. No skin atrophy or telangiectasia was found at the application sites of delgocitinib ointment. Application site irritation symptoms were infrequent (<2%) and mild. The incidence of AEs did not increase over time, except for seasonal diseases. The improvement effects on AD as assessed by mEASI were maintained throughout the treatment period. Delgocitinib 0.5% ointment was well tolerated and effective when administrated to Japanese adult patients with AD for up to 52 weeks.
| S-EPMC7028108 | biostudies-literature
Project description:IntroductionThe comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.MethodsThe systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.ResultsOf 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.DiscussionMany factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.ConclusionUpadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.
| S-EPMC9110624 | biostudies-literature
Project description:The skin produces cortisol by itself and regulates its own proliferation and differentiation. There is a possibility that topical corticosteroids (TCSs) influence the cortisol homeostasis in the skin.The author described the density and distribution of cortisol and its parties in the epidermis after application of topical steroids immunohistologically.The forearm skin was biopsied before and after 2 weeks' application of clobetasol propionate 0.05% two times a day in one healthy volunteer. The biopsied skin was stained immunohistologically by ant-MLN64, StAR, CPY11A1, cortisol, HSD11B1, HSD11B2, glucocorticoid receptor alpha, glucocorticoid receptor beta (GRB), and mineralocorticoid receptor (MCR) antibodies. The skin biopsy was performed similarly in 19 adult patients with atopic dermatitis who had used TCS for a considerable period. They were 4 TCS present users (TCS+), 12 TCS nonusers with skin manifestation on the biopsied site (TCS-E+) and 3 TCS nonusers without skin manifestation on the biopsied site (TCS-E-).The staining density increased during TCS application in MLN64, cortisol and HSD11B2 in a healthy volunteer. The staining density was stronger in HSD11B2 of the basal layer and MCR of the spinous layer in the TCS-E+ patients than in the TCS+ and TCS-E- patients. The staining density was weaker in MLN64 of the basal and granular layers, HSD11B1 of the basal layer and GRB of the whole layer in the TCS-E+ patients than in the TCS+ and TCS-E- patients.The hypertrophy of the epidermis and insufficient keratinization recognized in the TCS-E+ patients might be caused by the decreased cortisol synthesis regulated by MLN64 and the increased cortisol inactivation by HSD11B2. Decreased GRB and increased MCR might enhance the reactivity of cortisol in the keratinocytes.
| S-EPMC5527739 | biostudies-other
Project description:BackgroundAtopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood.AimsWe used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy.MethodsSeventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls.ResultsTCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF.ConclusionsThe profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy.
| S-EPMC8359435 | biostudies-literature
Project description:IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disorder that affects millions worldwide, presenting challenges in managing symptoms and quality of life. Current treatments include topical corticosteroids (TCS), but novel approaches, such as Janus kinase (JAK) inhibitors, show promise. Baricitinib, a selective JAK1 and JAK2 inhibitor, targets cytokines involved in AD and offers potential benefits beyond traditional therapies.MethodsA systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the efficacy and safety of baricitinib in treating moderate-to-severe AD. We followed PRISMA guidelines and assessed data from PubMed, Cochrane Central, ScienceDirect, and ClinicalTrials.gov up to August 2024. The analysis included trials comparing baricitinib to placebo, with or without TCS, evaluating outcomes such as Investigator's Global Assessment (IGA) scores, Eczema Area and Severity Index (EASI) scores, and safety profiles.ResultsSix RCTs involving 2,595 participants met the inclusion criteria. Baricitinib demonstrated significant improvements in IGA scores, EASI scores, Dermatology Life Quality Index (DLQI), and other outcome measures compared to placebo. The efficacy was consistent across different dosages (1 mg, 2 mg, 4 mg) and whether baricitinib was used with or without TCS. Safety analyses revealed a significant increase in treatment-emergent adverse events (TEAEs), particularly with the 2 mg and 4 mg dosages and with TCS.ConclusionBaricitinib, both alone and in combination with TCS, significantly improves symptoms and quality of life in patients with moderate-to-severe AD, with efficacy consistent across dosages. The safety profile is overall acceptable, though a significant increase in TEAEs was observed, particularly with higher dosages and when used with TCS. Ongoing monitoring of TEAEs is recommended, and future trials with longer follow-up periods are suggested to better understand long-term outcomes.
| S-EPMC11602504 | biostudies-literature
Project description:IntroductionAtopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD.MethodsA literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48-60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109.ResultsA total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3-92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3-89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7-75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs.DiscussionToday, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.
| S-EPMC9410312 | biostudies-literature
Project description:ImportanceBaricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies.ObjectiveTo assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy.Design, setting, and participantsThis double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study.InterventionsPatients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed.Main outcomes and measuresThe primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16.ResultsAmong 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis.Conclusions and relevanceA dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD.Trial registrationClinicalTrials.gov Identifier: NCT03733301.
| S-EPMC7527941 | biostudies-literature