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Advances in Therapy Feb 2024Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial... (Review)
Review
Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.
INTRODUCTION
Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib.
METHODS
MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022.
RESULTS
A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib.
CONCLUSION
Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.
Topics: Humans; Arthritis, Psoriatic; Arthritis, Rheumatoid; Colitis, Ulcerative; Heterocyclic Compounds, 3-Ring; Methotrexate; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 38169057
DOI: 10.1007/s12325-023-02732-6 -
Clinical and Translational Allergy Dec 2023Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as... (Review)
Review
BACKGROUND
Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first-line anti-inflammatory therapy for AD, but long-term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta-analysis to investigate whether MA as an add-on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD.
METHODS
We systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence.
RESULTS
A total of 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that compared with controls, oral MA as an add-on therapy was associated with significantly lower SCORAD scores (MD = -5.30, 95% CI -8.50, -1.55, p < 0.01, I = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta-analysis study (p > 0.05).
CONCLUSIONS
This meta-analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be used as an add-on therapy in the treatment of AD. However, due to the limited number of studies, results should be interpreted with caution. Further studies with a larger sample size are needed to explore the optimal protocol of MA plus TCS.
PubMed: 38146806
DOI: 10.1002/clt2.12318 -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793 -
The Journal of Dermatological Treatment Dec 2024Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing... (Review)
Review
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
Topics: Adult; Child; Humans; Methotrexate; Dermatitis, Atopic
PubMed: 38124505
DOI: 10.1080/09546634.2023.2292962 -
JMIR Dermatology Dec 2023Dermatological conditions, especially when severe, can lead to sleep disturbances that affect a patient's quality of life. However, limited research exists on the... (Review)
Review
BACKGROUND
Dermatological conditions, especially when severe, can lead to sleep disturbances that affect a patient's quality of life. However, limited research exists on the efficacy of treatments for improving sleep parameters in skin conditions.
OBJECTIVE
The objective was to perform a systematic review of the literature on dermatological conditions and the treatments available for improving sleep parameters.
METHODS
A literature review was performed using the PubMed, Ovid MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases from 1945 to 2021. After filtering based on our exclusion criteria, studies were graded using the SORT (Strength of Recommendation Taxonomy) algorithm, and only those receiving a grade of "2" or better were included.
RESULTS
In total, 25 treatment studies (n=11,025) assessing sleep parameters related to dermatological conditions were found. Dupilumab appeared to be the best-supported and most effective treatment for improving sleep in atopic dermatitis (AD) but had frequent adverse effects. Topical treatments for AD were mostly ineffective, but procedural treatments showed some promise. Treatments for other conditions appeared efficacious.
CONCLUSIONS
The evaluation of sleep parameter changes in dermatological treatments is predominantly restricted to AD. Systemic interventions such as dupilumab and procedural interventions were the most efficacious. Sleep changes in other dermatoses were limited by a paucity of available studies. The inclusion of a sleep assessment component to a broader range of dermatological treatment studies is warranted.
PubMed: 38090791
DOI: 10.2196/48713 -
BMJ Open Dec 2023External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to...
OBJECTIVES
External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs).
DESIGN
Systematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality.
DATA SOURCES
Embase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023.
ELIGIBILITY CRITERIA
Eligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors.
RESULTS
Forty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data.
CONCLUSIONS
Standardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research.
Topics: Adult; Humans; Spondylitis, Ankylosing; Pouchitis; Arthritis, Rheumatoid; Psoriasis; Inflammatory Bowel Diseases; Immunomodulating Agents
PubMed: 38070932
DOI: 10.1136/bmjopen-2023-076677 -
Heliyon Nov 2023In recent years, biologics targeting key cytokines and Janus kinase (JAK) inhibitors have demonstrated favorable efficacy and safety outcomes for atopic dermatitis (AD)...
BACKGROUND
In recent years, biologics targeting key cytokines and Janus kinase (JAK) inhibitors have demonstrated favorable efficacy and safety outcomes for atopic dermatitis (AD) therapy. To evaluate the short-term efficacy and safety of AD therapy involving biologics, JAK inhibitors, and their combination with topical corticosteroids (TCS) for patients with AD, we conducted this systematic review and meta-analysis. Using eligible randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD.
METHODS
PubMed, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception up to October 25, 2023. English-language randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD were included. Titles, abstracts, and articles were screened in duplicate. Of 7261 citations, 37 studies were included. The data were analyzed using Review Manager 5.4 and the outcomes were measured by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), the pruritus Numerical Rating Scale (NRS), as well as instances of adverse events (AE), and serious AE (SAE), which were presented as risk ratio (RR) with a 95 % confidence interval (CI). The efficacy of the biological therapies was analyzed with the percentage of patients who have achieved EASI 75, EASI 90, IGA 0/1 and pruritus NRS4, while the safety of treatments was evaluated in terms of the number of patients who had ≥1 AE and who had at least one SAE.
RESULTS
A total of 37 studies with 43 cohorts that examined 9 medications and placebo and involved 18172 participants were included. Compared with the placebo, all biologics and JAK inhibitors were associated with a higher response rate in efficacy outcomes, while systematic administration was presented by dupilumab 200 mg subcutaneously every 2 weeks with superior improvement in EASI 90 (RR 9.50, 95 % CI 2.31-39.03) and IGA0/1 (RR 17.00, 95 % CI 2.33-123.78), upadacitinib 30 mg once daily in EASI 75 (RR 5.14, 95 % CI 4.20-6.31) and Pruritus NRS4 (RR 5.73, 95 % CI 4.44-7.39), and external use was presented by ruxolitinib 1.5 % twice daily orally in EASI 75 (RR 4.14, 95 % CI 3.06-5.61) and Pruritus NRS4 (RR 4.08, 95 % CI 2.86-5.81), and most of doses led to a better safety profile. Most doses of baricitinib, dupilumab, tralokinumab, and upadacitinib in combination with TCS demonstrated good efficacy as compared with the control groups (placebo + TCS). However, patients receiving baricitinib at a dosage of 2 mg daily (RR 1.23, 95 % CI 1.02-1.49) and 4 mg daily (RR 1.39, 95 % CI 1.22-1.58) in combination with TCS, exhibited a higher incidence of one or more SAE as compared with those taking placebo + TCS.
CONCLUSION
Our research has revealed that ruxolitinib and dupilumab are effective and safe treatments for mild to moderate AD and moderate to severe AD, respectively. Additionally, the combination of dupilumab and TCS demonstrates greater efficacy and safety compared to baricitinib, tralokinumab, and upadacitinib with TCS as a background treatment for moderate to severe AD. We suggest that the use of topical JAK inhibitors could be a potential alternative to TCS when used in combination with systemic medications, as a novel approach to treat AD. Insufficient different data sources caused by partial interventions were only mentioned in a few articles and low event rates in safety analyses may lead to the results being biased. Further studies directly comparing existing and novel treatments are needed and will be included in forthcoming updates of this review. Our findings could form a useful foundation for developing a new generation of treatment guidelines for AD.
PubMed: 38034798
DOI: 10.1016/j.heliyon.2023.e22014 -
The Journal of Allergy and Clinical... Feb 2024The coronavirus disease 2019 (COVID-19) pandemic caused significant disruptions to health care services and health impacts on patients with atopic dermatitis (AD) and/or...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic caused significant disruptions to health care services and health impacts on patients with atopic dermatitis (AD) and/or food allergy (FA).
OBJECTIVE
We evaluated the impact of the COVID-19 pandemic and disease on AD/FA patients.
METHODS
A comprehensive systematic literature search was conducted from December 2019 to 2022. Screening and data extraction were done following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and the Mixed Methods Appraisal Tool, or MMAT, was used to assess risk of bias.
RESULTS
In total, 159 studies were included. Five of 7 studies reported no significant changes in overall incidence or prevalence of AD during the pandemic, although some studies noted an increase in the elderly and infants. Telehealth served as an effective alternative to face-to-face consultations, with mixed levels of patient and provider satisfaction. Dissatisfaction was most marked in patients with more severe disease, who thought that their disease was inadequately managed through telemedicine. Higher levels of general anxiety were recorded in both AD/FA patients and caregivers, and it was more pronounced in patients with severe disease. Most studies reported no significant differences in postvaccination adverse effects in AD patients; however, results were more varied in FA patients.
CONCLUSION
Our review identified the impact of COVID-19 pandemic- and disease-driven changes on AD/FA patients. Telemedicine is uniquely suited to manage atopic diseases, and hybrid care may be a suitable approach even in the postpandemic era. COVID-19 vaccines and biologics can be safely administered to patients with atopic diseases, with appropriate patient education to ensure continued care for high-risk patients.
PubMed: 38026506
DOI: 10.1016/j.jacig.2023.100181 -
JMIR Dermatology Nov 2023Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema.... (Review)
Review
BACKGROUND
Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema. Dissatisfaction with first-line therapies for AD, the desire to avoid steroids, and the extreme cost of effective biologics have created a demand for alternative treatment options such as oral vitamins and nutritional supplements.
OBJECTIVE
The purpose of this review was to assess the effectiveness of oral nutritional supplements, pre- and probiotics, and vitamin deficiencies and supplements on AD symptomology and clinical course.
METHODS
We searched Scopus, PubMed, and MEDLINE (Ovid interface) for English-language articles published between 1993 and 2023. The final search was conducted on June 22, 2023. The search terms comprised the following: "(Atopic Dermatitis or Atopic Eczema) AND (supplement OR vitamin OR mineral OR micronutrients OR Fish Oil OR Omega Fatty Acid OR Probiotics OR Prebiotics OR apple cider vinegar OR collagen OR herbal OR fiber)."
RESULTS
A total of 18 studies-3 (17%) evaluating vitamins, 4 (22%) evaluating herbal medicine compounds, 2 (11%) evaluating single-ingredient nutritional supplements, and 9 (50%) evaluating pre- and probiotics-involving 881 patients were included in this review.
CONCLUSIONS
Overall, there is weak evidence to support any one nutritional supplement intervention for the alleviation of AD symptoms. Multiple trials (4/18, 22%) showed promise for supplements such as Zemaphyte, kefir, and freeze-dried whey with Cuscuta campestris Yuncker extract. The most evidence was found on the effectiveness of probiotics on the clinical course of AD. Lactiplantibacillus plantarum, Ligilactobacillus salivarius, and Lactobacillus acidophilus specifically showed evidence of efficacy and safety across multiple studies (6/18, 33%). However, larger, more extensive randomized controlled trials are needed to determine the true effectiveness of these supplements on the broader population.
TRIAL REGISTRATION
PROSPERO CRD42023470596; https://tinyurl.com/4a9477u7.
PubMed: 38019566
DOI: 10.2196/40857 -
Dermatology Practical & Conceptual Oct 2023Atopic Dermatitis (AD) affects individuals from all ethnicities and backgrounds. It has the highest global disease burden of dermatoses. There is a widely held belief... (Review)
Review
INTRODUCTION
Atopic Dermatitis (AD) affects individuals from all ethnicities and backgrounds. It has the highest global disease burden of dermatoses. There is a widely held belief that the presentation of AD is not described well in individuals with non-European ancestry in peer-reviewed literature. However, to our knowledge, this has not been investigated previously.
OBJECTIVE
To quantify the number of peer-reviewed literature describing the appearance of clinical features of AD in non-European ancestry, particularly those originating from the Asian and African continents.
METHODS
A systematic scoping review between December 2020 and January 2021 was performed to quantify the number of studies describing AD in individuals of African and Asian ancestry.
RESULTS
Sixteen studies were identified. None of the studies provided a clear description of AD in our population groups. Two studies described features of lichen planus like-AD in African American individuals. All studies reported on observed clinical features of AD.
CONCLUSIONS
The review confirmed a lack of literature describing AD in populations of non-European heritage. It should encourage authors to make a deliberate effort to describe the appearance of clinical features of AD to enable understanding of how they may differentiate in individuals originating from different parts of the globe.
PubMed: 37992338
DOI: 10.5826/dpc.1304a259