Traditional Immunosuppressants Research Articles

Efficacy and safety of infliximab or adalimumab in severe mucocutaneous Behçet’s syndrome refractory to traditional immunosuppressants: a 6-month, multicentre, randomised controlled, prospective, parallel group, single-blind trial

IntroductionEvidence from randomised controlled trials on anti-tumour necrosis factor (TNF) agents in patients with Behçet’s syndrome (BS) is low.MethodWe conducted a phase 3, multicentre, prospective, randomised, active-controlled, parallel-group study to...

Systemic Therapy for Atopic Dermatitis in Children and Adolescents: A US Expert Consensus.

Atopic dermatitis (AD) is a chronic, type-2 mediated, inflammatory skin disease characterized by intense pruritus, disruption of skin barrier function, and immune dysregulation. Management strategies for AD are routinely determined based on disease severity. First-line treatment begins with basic skin care and topical anti-inflammatory medication, which is typically sufficient for the management of mild-to-moderate disease. For those patients with moderate-to-severe disease, systemic therapy is often required. This can involve off-label treatment with conventional immunosuppressant medications. However, this approach is limited by a lack of robust clinical trial data and safety concerns that necessitate close monitoring. The emergence of novel targeted biologics and small molecules to treat AD presents an opportunity to optimize AD management and patient outcomes by offering greater efficacy than traditional immunosuppressants and a favorable safety profile. As the treatment landscape shifts, clinicians can benefit from a standardized process of patient assessment and treatment, along with resources to help maintain contemporary knowledge of available therapeutic options. This US-based, expert-led consensus used a modified Delphi process to develop core recommendations for the use of systemic medications for the management of pediatric patients <18 years of age with moderate-to-severe AD.

Expanding the spectrum of IPEX: from new clinical findings to novel treatments.

This review aims to provide an overview of recent research findings regarding immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, focusing on clinical and immunological novelties, as well as emerging treatment strategies, based on the published literature of the last few years. While it is well known that IPEX can present with a wide range of atypical clinical manifestations, new and unique phenotypes continue to emerge, making it essential to maintain a high level of clinical suspicion both at the time of diagnosis and during follow-up. This unpredictability in clinical presentation is further compounded by the lack of a clear genotype-phenotype correlation. A valuable tool for monitoring comes from recent discoveries regarding the epigenetic signature of Tregs, which, by correlating with disease severity, could prove to be a useful biomarker for diagnosis and ongoing management. The use of biological agents is emerging as an alternative to traditional immunosuppression. Additionally, ongoing studies are exploring the feasibility of gene therapy through the introduction of the wild-type FOXP3 into peripheral CD4 + T cells. Further research is needed to fully understand the variable clinical presentations of IPEX and optimize tailored therapies, ensuring better management and outcomes for affected individuals.

Efficacy and safety of a step-down regimen of low dosage of glucocorticoids combined with early administration of synthetic or biologic immunosuppressants in anti-synthetase syndrome: A pilot study

IntroductionAnti-synthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of anti-aminoacyl-transfer-RNA synthetase antibodies (ARS) and the involvement of muscles, skin, joints, and lungs. Despite increasing interest and evidence, optimal clinical management remains unclear due to a lack of randomized control trials. This study aims to evaluate the efficacy and safety of a treatment regimen involving early co-administration of glucocorticoids and immunosuppressants, with rapid prednisone tapering. Materials and methodsWe prospectively enrolled patients referred to our multidisciplinary “Myositis Clinic” with a diagnosis of ASS. Clinical, serological, instrumental and medications data were collected at baseline and at 6 and 12 months follow-up. According to treatment protocol, patients were treated with traditional synthetic immunosuppressants or rituximab (RTX) depending on clinical manifestations. Prednisone (PDN) was gradually tapered and eventually discontinued within 6 or 12 months. ResultsA total of twenty-seven subjects were enrolled: arthritis, myositis and ILD were assessed in 9, 16 and 18 patients, respectively, and all of them had an active disease. RTX was administered after methotrexate (MTX) in 4 cases of refractory joint involvement and co-administration of a second immunosuppressant was necessary in 2 patients. When muscle involvement was present, first-line therapy was MTX, followed by mycophenolate mofetil (MMF) or RTX, which allowed to achieve low disease activity or remission, respectively. Eight ILD-patients were treated with MMF and switched to RTX in 5 cases of inefficacy, but all patients were in clinical remission at the end of follow-up. At 12 months, 12 patients discontinued PDN. ConclusionsThis study is the first to prospectively report on the efficacy and safety of a stepwise, steroid-sparing treatment ASS encompassing various domains. MTX, as well as other synthetic immunosuppressants, showed limited efficacy in ASS-related arthritis, while RTX emerged as a promising option. This study recommends early RTX use in case of arthritis, suggesting it as a pivotal treatment for ILD too, and raises questions regarding maintenance therapy and treatment-free remission.

From traditional to targeted: the changing trajectory of therapies in dermatomyositis.

New breakthroughs in our understanding of dermatomyositis (DM) have spawned the recent development of novel agents that specifically target key drivers in DM immunopathogenesis. This review aims to provide a comprehensive overview of new and forthcoming therapies for DM and to highlight their mechanisms of action, best evidence to date, and potential impact on disease management. Strategies that either counteract dysregulated interferon signaling [via the inhibition of interferon β, the type I interferon receptor subunit 1 (IFNAR1), or janus kinase (JAK)-signal transducer and activator of transcription (STAT) transduction] or induce durable autoreactive B cell depletion through chimeric antigen receptor (CAR) T-cell therapy appear to hold the most promise for sustained remission in DM. The trajectory of DM treatments is rapidly evolving, fueled by the unparalleled insights provided by multiomic studies and big data analysis pipelines. Targeted therapies that maximize both efficacy and safety have the potential to complement or replace traditional immunosuppressives and revolutionize the approach to the management of DM.

Management of Guttate Psoriasis: A Systematic Review.

Guttate psoriasis (GP) is a variant of psoriasis characterized by scattered "drop-like" papules and plaques, accounting for up to a quarter of psoriasis cases. Although GP can clear within 3 to 4 months, up to 39% of cases may progress to chronic plaque psoriasis. Currently, there is a paucity of literature investigating the efficacy of different treatment modalities. This systematic review aims to synthesize all available data on GP treatment efficacy. A literature search was conducted using Medline, Embase, Web of Science, and CINAHL with no date limits. A total of 75 studies satisfied eligibility criteria and were analyzed. Most studies were case reports, series, or retrospective studies. Only 5 randomized controlled trials (RCTs) were identified. For topical treatments, corticosteroids and calcipotriol creams had the most evidence for efficacy. Four categories of systemic therapies were identified: traditional immunosuppressants, antibiotics, retinoids, and biologics. Evidence regarding antibiotic therapy suggests minimal connection between underlying infection resolution and GP lesion remission. Phototherapy had the most robust evidence, with narrowband ultraviolet B (UVB) being the most effective. Our findings are limited by high heterogeneity in study design and high risk of bias. Based on our review, we propose the following treatment algorithm. As first-line therapy, we recommend topical corticosteroids and calcipotriol cream, in combination with phototherapy. As supportive therapy, we recommend antibiotics if applicable. For second-line therapy, we recommend methotrexate or cyclosporine. For severe and refractory GP, biologics can be used as third-line treatment. RCTs are needed to provide higher quality evidence to create standardized treatment recommendations.

Blocking the IL-4/IL-13 Axis versus the JAK/STAT Pathway in Atopic Dermatitis: How Can We Choose?

Atopic dermatitis (AD) is an immune-mediated skin disorder with a chronic-relapsing course and a multifactorial pathogenesis. In contrast to the traditional concept of AD as solely a type 2 immune-activated disease, new findings highlight the disease as highly heterogeneous, as it can be classified into variable phenotypes based on clinical/epidemiological or molecular parameters. For many years, the only therapeutic option for moderate-severe AD was traditional immunosuppressive drugs. Recently, the area of systemic therapy of AD has significantly flourished, and many new substances are now marketed, licensed, or in the last step of clinical development. Biological agents and small molecules have enriched the therapeutic armamentarium of moderate-to-severe AD, such as dupilumab, tralokinumab, lebrikizumab (monoclonal antibodies targeting the IL-4/13 pathway), abrocitinib, upadacitinib, and baricitinib (JAK inhibitors). Indeed, the AD treatment paradigm is now split into two main approaches: targeting the IL-4/13 axis or the JAK/STAT pathway. Both approaches are valid and have strong evidence of preclinical and clinical efficacy. Therefore, the choice between the two can often be difficult and represents a major challenge for dermatologists. Indeed, several important factors must be taken into account, such as the heterogeneity of AD and its classification in phenotypes, patients' comorbidities, age, and personal preferences. The aim of our review is to provide an overview of the clinical and molecular heterogeneities of AD and to explore the factors and parameters that, in clinical practice, may help inform clinical decision-making.

The use of low-level lasers in the treatment of oral lichen planus (OLP) – a review of the literature

A laser is a device that emits radiation in the visible light, ultraviolet or infrared range, using the phenomenon of forced emission. The name is an acronym for Light Amplification by Stimulated Emission of Radiation. The main characteristics of a laser beam include: monochromaticity, coherence, parallelism and intensity. By power, we can divide lasers into 2 groups: high-energy (hard) lasers with emission power above 1 W and low-energy (&lt;1 W) lasers. Lasers are used in medicine, industry, military technology, telecommunications, surveying and construction, among other fields. Lichen planus is a chronic disease of the mucous membranes and skin with a fairly common occurrence, characteristic clinical picture and unclear etiology. The therapy of lichen planus of the mucous membranes, especially its oral form (OLP), is still a major problem despite continuous medical advances. To date, a fully effective treatment regimen has not been developed. Current methods are mainly based on pharmacotherapy. With advances in technology, the search for alternative forms of treatment has begun. In recent years, an increasing number of reports have suggested the validity of using Low Level Laser Therapy (LLLT) to treat oral lichen planus. The use of this treatment may reduce the incidence of side effects observed with traditional corticosteroid (CS) therapy, sulfones or immunosuppressants.

Exploring susceptibility factors to medication dispensing errors through a retrospective study of patient-reported dispensing errors over 11 years: are dispensing errors indeed due to personal reasons for pharmacists?

BackgroundMedication dispensing errors cause wastage of medicines and increase healthcare costs, with serious consequences for patients. However, few studies have systematically and completely reviewed dispensing errors, with inadequate attention to...

Systematic Review with Meta-analysis: Efficacy and Safety of Upadacitinib in Managing Moderate-to-Severe Crohn's Disease and Ulcerative Colitis.

In the panorama of therapeutic strategies for inflammatory bowel diseases, oral upadacitinib stands out for its potential to improve short-term and long-term patient outcomes. This meta-analysis aspires to collate and assess the available evidence regarding the efficacy and safety of upadacitinib in managing moderate-to-severe Crohn's disease and ulcerative colitis. A meta-analysis was conducted using studies sourced from MEDLINE/PubMed, Cochrane Library, Scopus, and Embase, published from January 2010 to March 2024. Peer-reviewed articles that reported data on the effects of upadacitinib in adult patients with Crohn's disease and ulcerative colitis were included based on established inclusion and exclusion criteria. Eight studies, encompassing a total of 2818 patients treated with upadacitinib, were included. In primary outcomes, for patients with Crohn's disease who were using upadacitinib, the weighted pooled clinical remission rate was found to be 45.8% (95% confidence interval [CI] 0.39-0.52), while for patients with ulcerative colitis who were using upadacitinib, the rate was 25.4% (95% CI 0.17-0.36). The pooled clinical response rate for Crohn's disease was 53.6% (95% CI 0.50-0.57), and for ulcerative colitis it was 72.6% (95% CI 0.69-0.76). The pooled serious adverse event rate was 6.0% (95% CI 0.07-0.09). Upadacitinib demonstrates significant efficacy in achieving clinical remission and response in patients with moderate-to-severe Crohn's disease and ulcerative colitis, as shown by clinical remission rates of 44.9% and 36.0%, respectively. The treatment also maintains a favorable safety profile with a serious adverse event rate of 7.8%, making it an effective option for those resistant or intolerant to traditional immunosuppressants or tumor necrosis factor antagonists.

Rituximab treatment in resistant lupusnephritis: A single-center prospective study.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and failure to respond to traditional immunosuppression increases morbidity and mortality. Rituximab has been considered a novel therapeutic option for the management of SLE. We conducted a single-center, prospective, observational study from July 2018 to June 2019 to evaluate the effectiveness of rituximab in patients with resistant LN. Resistant LN was defined as the failure to respond to conventional immunosuppressive therapy including both cyclophosphamide and mycophenolate mofetil. All adult patients (>18 years) with biopsy-proven class III/IV LN were included in the study. Four doses of intravenous rituximab (375 mg/m2) on 0, 1, 2, 3 weeks were administered. Patients were followed for 6months, and the rates of complete renal response (CRR), partial renal response (PRR), or no renal response (NRR) were measured. The change in baseline 24-hour urine protein, mean serum creatinine levels, and mean serum CD-19 levels at 24 weeks were also measured. Six months after rituximab therapy, total sustained renal response (CRR+PRR) was observed in 52% cases of resistant LN (CRR was achieved in 24% of patients and PRR in 28%, respectively). Rituximab was associated with a significant decline in the 24-hour urine protein, even in non-responders. However, the improvement in eGFR and serum creatinine was not statistically significant. The mean absolute CD-19 count was significantly low in responders compared to the non-responder group. Rituximab is a safe and effective therapeutic strategy for patients with resistant LN.

Targeted treatments for immune dysregulation in inborn errors of immunity

Primary immune regulatory disorders (PIRDs) constitute a subset of inborn errors of immunity and are characterized by lymphoproliferation, autoimmunity, malignancy, and infection. Unlike classical primary immune deficiencies, initial symptoms of PIRDs can manifest as autoimmunity such as cytopenias or enteropathy, which can often prove resistant to conventional treatments and occur years prior to the onset of infectious complications. Raising awareness about PIRDs among specialists and adopting a multidisciplinary approach is crucial for early diagnosis, intervention, and potential prevention of severe organ damage. Significant progress has been made in identifying several PIRDs, which has contributed to a more comprehensive comprehension of their underlying immunological mechanisms. This knowledge has paved the way for targeted therapies focusing on specific molecules, which tend to offer superior disease control compared to traditional immunosuppressants. This review, informed by the latest literature, explores prevalent PIRDs, detailing their clinical manifestations and recent advancements in treatment modalities.

Dawn of CAR-T cell therapy in autoimmune diseases.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo , CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Data mining and safety analysis of traditional immunosuppressive drugs: a pharmacovigilance investigation based on the FAERS database

ABSTRACT Objective The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned. Methods The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs. Results Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia. Conclusion The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies. Expert opinion The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.

Optimizing Behçet Uveitis Management: A Review of Personalized Immunosuppressive Strategies.

Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible visual impairment and an elevated risk of blindness. This review synthesizes contemporary insights into personalized immunosuppressive strategies for Behçet uveitis, emphasizing the necessity for a customized approach in recognition of the disease's heterogeneity and the variable responsiveness to treatment. This discourse elaborates on the application, efficacy, and safety profiles of traditional immunosuppressants, highlighting a paradigm shift toward integrative combination therapies aimed at diminishing reliance on glucocorticoids and mitigating their associated adverse effects. This thorough evaluation seeks to enlighten clinical practices and spearhead future investigations aimed at refining the management of Behçet uveitis, championing a personalized, multidisciplinary strategy to amplify therapeutic efficacy and enhance patient quality of life.

P19 Our experience diagnosing and treating deficiency of adenine deaminase 2 (DADA2) vasculitis

Abstract Introduction Deficiency of adenine deaminase 2 (DADA2) is caused by biallelic pathogenic variants in the gene on chromosome 22q11. It is autosomal recessive with incomplete penetrance, and a variable presentation. It typically manifests as a systemic vasculopathy with early onset strokes, cutaneous manifestations, immunodeficiency and cytopenia. Traditional immunosuppressants have limited efficacy, but vasculitic manifestations have been reported to respond to biologic TNF-inhibitors. We report a patient with confirmed ADA2 deficiency whose cutaneous manifestations were previously classified as Sneddon syndrome. After a period of stability on adalimumab she developed marked cutaneous ulceration that healed following a therapy switch to intravenous infliximab. Case description We report a 39-year-old female with a long clinical history that started in childhood when she developed Diamond-Blackfan anaemia that went into remission following corticosteroid treatment and transfusions. In 2006, she suddenly had two thalamic infarcts and was thoroughly investigated but was found to have unremarkable vascular imaging, a negative antiphospholipid syndrome and autoantibody testing, a modestly elevated CRP (5-15 mg/L) and a notably persistent low serum IgM. She continued to experience frequent migraines associated with transient sensorimotor symptoms. Subsequently, she developed recurrent botchy, polymorphic macular eruptions on the lower limbs. A deep cutaneous biopsy demonstrated lymphocytic predominant perivascular inflammation of deep dermal vessels associated with thrombus formation and endothelial proliferation. A putative diagnosis of Sneddon’s syndrome was made. However, after the subsequent identification of ADA2-deficiency vasculitis, the patient underwent genetic screening which identified a compound heterozygosity for two novel ADA2 mutations (c6634_636, delTTC (p.Phe212del) and c.1225C&amp;gt;T (p.Pro409Ser)). Her mother was as a carrier. She was started on adalimumab injections to which she had a good clinical response with improved cutaneous disease and no further neurological symptoms. However, after two years of disease stability, she then developed a significant ‘punched out’ ulcer on the mid-calf which was painful and increasing in size to a maximum of 2 x 3 cm. Dermatology colleagues were reluctant to re-biopsy due to a high likelihood of non-specific appearances and increased risk of poor healing leading to worsening ulceration. Drawing on experience from rheumatoid arthritis that a switch in anti-TNF biological will often restore efficacy following secondary non-response to adalimumab; we empirically switched treatment to intravenous infliximab, with a reducing course of prednisolone (40mg per day tapering to 5mg after 12 weeks). This was associated with a notable improvement within one month and a complete healing of the ulcer within 4 months. Discussion DADA2 remains a rare condition with a carrier frequency estimated at 1 in 236 persons worldwide and a predicted disease prevalence of approximately 1 in 222,000 persons. Patients with DADA2 who have haematological manifestations tend to present during early infancy, whereas delayed presentation is common in patients with vasculitis and systemic inflammation. It should be suspected in patients with early onset strokes, livedo and other haematological and immunological features. Additionally, many previously diagnosed cases of Sneddon syndrome may in fact have DADA2, with a low IgM level favouring the later. Diagnosis can be confirmed by genetic studies or by a biochemical assay that demonstrates near-absent levels of ADA2 activity in the plasma or serum. Interestingly, on screening of adult patients with polyarteritis nodosa (PAN) 3.4% possessed biallelic pathogenic ADA2 variants and similarly, in genomic survey of patients with Diamond-Blackfan anaemia 2% possessed biallelic pathogenic ADA2 variants in the absence of the ribosomal protein gene mutations associated with it. Treatment is phenotype based with a preference for lifelong TNF inhibitor and biosimilar use in those with vasculitis and/or systemic inflammation, though not currently commissioned for this indication. Glucocorticoids, disease-modifying antirheumatic drugs, and other biologic agents may partially ameliorate systemic inflammation. Unfortunately, they are all ineffective for severe hematologic manifestations and hematopoietic cell transplantation (HCT) is currently the only treatment option. Treating asymptomatic patients and mildly symptomatic patients picked up on screening remains senior clinician led on a risk benefit basis. Disease activity is clinically monitored with an overall mortality rate estimated at 8%. Key learning points The main learning points for me included an increased awareness of this syndrome, its variable presentation, association with other autoimmune illnesses, diagnosis, and treatment initiation. In addition, I learnt about screening of family members, weighing the benefits versus risks when considering treating mildly symptomatic and asymptomatic patients, clinical monitoring for response, and when to switch to other anti-TNFs and biosimilars. From this conference, I would like to explore the experience of our rheumatology colleagues with similar cases.

Janus kinase inhibitors in autoimmune bullous diseases.

Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred treatment for AIBD involves the use of glucocorticoids or traditional immunosuppressants. Additionally, the utilization of biological agents such as rituximab, omalizumab, and dupilumab is on the rise. However, effectively managing AIBD remains a challenge. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been implicated in various inflammatory diseases. In recent years, a range of drugs known as JAK inhibitors, which target this pathway, have been developed. Several studies have explored the efficacy and safety of JAK inhibitors for treating AIBD. Consequently, this review begins by examining the role of the JAK/STAT pathway in AIBD, summarizing the application of different JAK inhibitors in AIBD treatment, and emphasizing the importance of disease management in treating AIBD with JAK inhibitors. Furthermore, it highlights the need for a better understanding of the JAK/STAT pathway's role in AIBD, as well as the effectiveness and safety of JAK inhibitors for treating this disease.

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200mg and 100mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200mg) than dupilumab at week2. This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a posthoc analysis of the JADE COMPARE trial. Adults with moderate-to-severe AD received once-daily oral abrocitinib 200mg or 100mg, dupilumab 300mg subcutaneous injection every 2weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥2-point improvement from baseline, ≥75% and ≥90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days2-15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week16. The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200mg than placebo (nominal p <0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200mg than placebo (nominal p <0.01); the time to achieve this response was shorter with abrocitinib 200mg (range 4.5-6.0days) than abrocitinib 100mg (range 5.0-17.0days), dupilumab (range 8.0-11.0 days), and placebo (range 3.0-11.5days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200mg than placebo (nominal p <0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. ClinicalTrials.gov, NCT03720470.

Pulmonary and central nervous system nocardiosis: Alcoholism as an immunocompromising factor

Nocardiosis is a disease with worldwide distribution. It is usually found in tropical areas and mainly affects immunocompromised patients, however, there are also cases where its infection has been reported in immunocompetent patients. This pathology is caused by bacteria known as Nocardia spp., which are gram-positive microorganisms and environmental saprophytes, and although exposure to Nocardia spp. is almost universal, only a small fraction of exposed people develops the disease. We present the case of a 47-year-old man, with no evidence of immunosuppression, from a rural area of Boyacá, who was admitted due to intense and intermittent headache accompanied by paresthesia and, finally, a decrease in consciousness. A brain magnetic resonance was performed and evidenced a fronto-temporo- occipital space-occupying lesion in the cortico-subcortical region with a compressive effect and displacement of the ventricular system cavities. It was suspected at first a neoplastic lesion or a brain abscess. The lesion was surgically resected, and its culture showed Nocardia africana/nova. In later studies a possible primary pulmonary focus was evidenced. Alcoholism was the only risk factor documented. The patient completed 6 weeks of hospital antibiotic treatment with favorable clinical and radiological evolution and was discharged with a 1-year plan of outpatient antibiotic therapy. Although Nocardia spp. mainly affects immunocompromised patients, evidence shows that this microorganism can also be a threat to individuals without traditional immunosuppression risk factors.

Takayasu arteritis and large-vessel giant cell arteritis in Italian population. Comprehensive analysis from a single institutional cohort of 184 cases

ObjectiveTo compare clinical and imaging characteristics in patients with Takayasu arteritis (TAK) and large vessel-giant cell arteritis (LV-GCA) in an Italian population. MethodsWe conducted a retrospective monocenter study comparing characteristics and outcomes of a cohort of 59 patients with TAK and a cohort of 127 patients with LV-GCA diagnosed between 1996 and 2016. Most of them (92%) were followed up for at least 24 months at Reggio Emilia Hospital (Italy). We also reviewed the literature discussing the results of the published manuscripts comparing LV-GCA to TAK ResultsLV-GCA patients had a higher prevalence of males (p = 0.003), and more frequently presented with cranial symptoms (p = 0.001), fever ≥38 °C (p = 0.007), polymyalgia rheumatica (p = 0.001), and hypertension (p = 0.001), and they had higher ESR levels at diagnosis (p = 0.0001). Differently, TAK patients had longer delay to diagnosis from the beginning of symptoms (p = 0.048), they presented more frequently with loss of pulses of large arteries (p = 0.0001), vascular bruits (p = 0.001), limb claudication (p = 0.003), myocardial infarction/angina (p = 0.03), and hypertension induced by renal artery stenosis (p = 0.001). Regarding treatment, TAK patients received a higher total and at 1 year cumulative prednisone doses (p = 0.0001 and p = 0.001, respectively), they had a longer duration of prednisone therapy (p = 0.008), and received during follow-up more frequently traditional immunosuppressants (p = 0.0001) and biological agents (p = 0.0001). Flares were more frequently observed in TAK patient (p = 0.001), while no differences were observed for long-term remission. New vascular procedures during the follow-up were more frequently performed in TAK patients (p = 0.0001). Regarding imaging at diagnosis, TAK patients had more frequently vascular stenosis/occlusion (p = 0.0001) and a higher number of vessels with structural damage per person (p = 0.0001), while LV-GCA patients had a higher number of inflamed vessels per person (p = 0.0001).Comparing the involved vascular districts at diagnosis for the presence of vessel inflammation and/or arterial damage, patients with LV-GCA had a more frequent involvement of thoracic and abdominal aorta (p = 0.024 and p = 0.007, respectively), and axillary, iliac and femoral arteries (p = 0.018, p = 0.002, and p = 0.0001. respectively), while in TAK patients, brachiocephalic, celiac, mesenteric and renal arteries were more frequently involved (p = 0.011, p = 0.019, p = 0.019, and p = 0.005, respectively). At imaging arterial damage at diagnosis was more frequently observed in TAK patients, specifically at common carotid, brachiocephalic, and subclavian arteries (p = 0.0001, p = 0.006, p = 0.0001, respectively) and descending aorta (p = 0.022). Regarding imaging during the follow-up, TAK patients developed more frequently new vascular stenosis/occlusion (p = 0.0001) and new vascular thickening (p = 0.002), no differences were observed for the development of new dilatation/aneurysm between the two vasculitides. ConclusionPatients with TAK and LV-GCA show a number of similarities and also differences. Indeed, it is unclear whether they are part of the same disease spectrum or they are different conditions. As more information regarding the pathogenesis and etiology becomes known, answers to these questions are like to be forthcoming.