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Background: Novel therapies for cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) demonstrated efficacy and safety in previous trials. However, data on the comparison of these treatments is still lacking, limiting their integration into clinical practice. Therefore, our aim is to perform a systematic review and network meta-analysis to compare the efficacy and safety of novel systemic therapies in CLE., Methods: A systematic search was performed across PubMed, Embase, and CENTRAL on November 25, 2023, to identify studies involving patients with CLE or SLE with active skin involvement treated with novel systemic therapies. The primary outcomes assessed were the proportion of patients achieving the Cutaneous Lupus Erythematosus Disease Area and Severity Index-50 (CLASI-50), the change in CLASI-A, the occurrence of adverse events (AEs), and serious adverse events (SAEs)., Results: 18,280 records were retrieved, of which 53 met the inclusion criteria. Deucravacitinib showed significantly greater efficacy in achieving the CLASI50 compared to placebo (OR: 8.28, 95 % CI: 2.22-30.91). Both litifilimab (OR: 2.54, 95 % CI: 1.20-5.40) and anifrolumab (OR: 2.25, 95 % CI: 1.23-4.14) were also significantly more effective than placebo. No significant differences were observed in the occurrence of AEs and SAEs between these therapeutics and placebo., Conclusion: Anifrolumab and litifilimab are effective and safe treatment options in CLE. However, deucravacitinib demonstrated superior efficacy and safety with fewer adverse events compared to anifrolumab. CLE patients who have shown an inadequate response to first- and second-line treatments may benefit from the incorporation of deucravacitinib into their treatment regimens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence regarding their efficacy and safety in systemic and cutaneous lupus erythematosus. We searched for systemic and cutaneous lupus erythematosus patients who were treated with JAK inhibitors in PubMed, Embase, Web of Science, and the Cochrane Library until February 28, 2023. The quality of clinical trials was assessed using the Cochrane risk-of-bias tool. Meta-analysis was conducted when at least three studies had comparable measures of outcome. If meta-analysis was not feasible, a descriptive review was carried out. We included 30 studies, consisting of 10 randomized controlled trials and 20 case series or reports, with a total of 2,460 patients. JAK inhibitors were found to be more effective than placebo in systemic lupus erythematosus (SLE) based on the percentage of achieving SLE Responder Index (SRI)-4 response (RR = 1.18; 95% CI 1.07 to 1.31; p = 0.001), British Isles Lupus Assessment Group -based Composite Lupus Assessment (BICLA) response (RR = 1.16; 95% CI 1.02 to 1.31; p = 0.02), Lupus Low Disease Activity State (LLDAS) (RR = 1.28; 95% CI 1.07 to 1.54; p = 0.008), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) remission of arthritis or rash (RR = 1.09; 95% CI 1.00 to 1.18; p = 0.04), particularly in treating musculoskeletal and mucocutaneous involvement. However, the effect of JAK inhibitors on cutaneous lupus erythematosus was uncertain. JAK inhibitors and placebo had a similar incidence of adverse events (RR = 1.01; 95% CI 0.97 to 1.04; p = 0.65). JAK inhibitors could be a potential treatment option for systemic and cutaneous lupus erythematosus, particularly in treating cutaneous and musculoskeletal lesions of SLE. JAK inhibitors had a safe profile. • JAK inhibitors were approved for use in various autoimmune diseases but did not include lupus. • JAK inhibitors were superior to placebo in managing systemic lupus erythematosus. • JAK inhibitors were effective in treating musculoskeletal and mucocutaneous involvement. • JAK inhibitors had poor effects on lupus nephritis and serological activity. • The efficacy of JAK inhibitors on cutaneous lupus erythematosus was uncertain. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) can be an individual disease only involving skin, or presents as part of the manifestations of SLE. A small proportion of CLE may progress into SLE, however, the underlying pathogenic mediators remain elusive. By only including researches that clearly described if the subtypes of CLE presented by enrolled subjects was associated with or without SLE, we provided an overview of antibodies, inflammatory cells and inflammatory molecular mediators identified in blood and skin that were possibly involved in lupus skin damages. IgG autoantibodies are crucial for the development of CLE associated with SLE, but the circulating inflammatory cells and molecular mediators require further studies to provide definitive proof for their association with skin damages. Discoid lupus erythematosus (DLE) is the most common subtype of CLE. For DLE without associated with SLE (CDLE), it is lack of evidences if autoantibodies and circulating inflammatory cells are involved in the pathogenesis or not, but is clear that the cutaneous inflammatory infiltrates are dominated by Th1, but not Th17 cells in contrast to the various complex profile in SLE. As the major target cells in skin, keratinocytes may participate the pathophysiological process by increase cell apoptosis and the production of proinflammatory cytokines in SLE and CDLE. Insights into the similarities and differences of the pathogenesis of CLE and CLE associated with SLE will also improve our therapeutic strategies for CLE that is currently adopted from SLE, and prevent the progression of CLE to SLE by providing interventions within an appropriate window of disease development. [ABSTRACT FROM AUTHOR]

Abstract: In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and Sjögren´s Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe. [Copyright &y& Elsevier]

Abstract: A study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) developed a Core Set Questionnaire for the evaluation of patients with cutaneous lupus erythematosus (CLE). The aim of the EUSCLE Core Set Questionnaire is to gain a broad and comparable data collection of patients with CLE from different European centers, to achieve consensus concerning evidence-based clinical standards for disease assessment, and to develop diagnostic and therapeutic guidelines. The authors designed the EUSCLE Core Set Questionnaire by including parameters considered most relevant for the evaluation of CLE and compiled from international literature, clinical praxis, and long-term experience with this disease. The compilation of the different parameters for the evaluation of CLE resulted in the 4-sided EUSCLE Core Set Questionnaire with six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. Thus, the EUSCLE Core Set Questionnaire for CLE constitutes a useful tool for the collection and evaluation of epidemiological data from patients with this disease. It enables consistent statistical evaluation, exchange, and comparison of patient''s data within several European countries and provides a set of guidelines for standardized diagnostic and therapeutic strategies in CLE. [Copyright &y& Elsevier]

Abstract: For a long time, systemic lupus erythematosus (SLE) was considered a potentially deadly disease. Since the introduction of immunosuppressive therapy, the life expectancy and the quality of life of patients suffering from lupus erythematosus has been dramatically improved. Today, the 5-year survival rate for SLE varies between 50% and 95%. Still, not all patients benefit equally from medical advances. Ethnic and/or socioeconomic minorities show severely disadvantageous prognosis or outcome in various studies. A substantial reduction in the quality of life as well as unemployment are other frequent side effects of this disease. Vocational handicaps related to discoid lupus erythematodes (DLE) was seen in nearly 45% of the patients. Therefore, the management of lupus erythematosus patients requires interdisciplinary cooperation between physicians, psychologists and social workers. The major aim of this article is to summarize the history of lupus erythematosus on the one and the other hand to consider the role of the socioeconomic factors influencing the prognosis of systemic and cutaneous lupus erythematosus. [Copyright &y& Elsevier]

Patients with systemic lupus erythematosus (SLE) have a high burden of cardiovascular disease (CVD) of multifactorial origin. The aim of this systematic review is to analyze the role of the interferon I (IFN-I) signature and fibroblast growth factor-23 (FGF-23) in patients with SLE or cutaneous lupus erythematosus (CLE) herein. We conducted a systematic literature search in PubMed and Scopus using keywords for major adverse cardiovascular events (MACE) and intermediate outcomes (endothelial dysfunction, subclinical atherosclerosis, platelet activation) associated with IFN-I or FGF-23 in patients with SLE and CLE. 4745 citations were screened, of which 12 studies were included. IFN-I was associated with MACE in two third of the studies and the association was strongest for cardiac events. An association of IFN-I was found in all studies investigating impaired vascular function, but only in 50% (respectively 40%) of reports examining the relation of IFN-I and platelet activation (respectively subclinical atherosclerosis). Altogether the reports were of variable bias and quality due to high variability of examined IFN-I biomarkers and inconsistent results for different outcome measures. No studies investigating the cardiovascular risk of circulating IFN-I in CLE, nor FGF-23 in SLE or CLE were found. Clinical studies measuring the association between IFN-I and direct / intermediate measures of CVD are rare and ambiguous in SLE and nonexistent in CLE, hampering a definite conclusion. • No studies of cardiovascular risk of systemic Interferon-I in cutaneous lupus • Interferon-I not an undisputed independent cardiovascular risk factor in systemic lupus • Indirect cardiovascular effect of interferon type I in lupus is possible [ABSTRACT FROM AUTHOR]