Polyarteritis nodosa mimics Kawasaki disease.

Polyarteritis nodosa (PAN) is a rarely seen vasculitis that often affects small-sized and medium-sized arteries. PAN can present with diverse clinical features depending on the organs involved, including potential cardiac involvement. Typical cardiac manifestations of PAN in the paediatric age group include pericarditis, valvular heart disease and coronary artery aneurysms. In contrast to PAN, Kawasaki disease (KD) is often associated with coronary artery abnormalities. Herein, we report a case of a young boy presented with KD-like features, including a coronary artery aneurysm confirmed by an echocardiogram (ECHO) and eventually diagnosed as PAN. The patient was treated with steroids, methotrexate and tocilizumab with improvement of the symptoms. Repeated ECHO revealed the resolution of the coronary artery aneurysms. Our paper highlights a rare presentation of PAN mimicking KD presentation. Physicians should consider PAN in chronic or severe courses of KD or coronary artery aneurysms.

Pathomechanism of Adverse Reactions to Biological Treatment of Inflammatory Skin Conditions.

Biological agents are widely used across medicine, including for immune-mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased. Herein, we discuss the pathomechanism of adverse reactions to biological agents used to treat skin conditions and apply these to Pichler's classification system. This classification differentiates five distinct types, namely overstimulation (type α), hypersensitivity or immunogenicity (ß), immunodeviation (γ), cross-reactivity (δ) and nonimmunologic adverse reactions (ε). This classification covers most types of adverse reactions associated with use of biological agents and could be used to better understand the reaction pathogenesis and manage the clinical features of biological adverse effects.

The potential role of fatigue in difficult-to-treat rheumatoid arthritis.

OBJECTIVES: A subset of patients with rheumatoid arthritis (RA) who remains symptomatic after failing to multiple drugs are deemed to have "difficult-to-treat RA" (D2T RA). Fatigue is a burdensome symptom for RA patients, hindering their improvement. Our purpose was to evaluate the role of fatigue in D2T RA. METHODS: This cross-sectional study included rheumatoid arthritis (RA) patients between 2018 and 2022, treated with biological agents or targeted synthetic disease-modifying antirheumatic drugs. D2T RA was defined attending EULAR criteria. Independent variable was fatigue (dimensions and impact) assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire and Numerical Rating Scales. Covariables: sociodemographic, clinical and treatment. To identify factors independently associated to D2T RA, multivariable logistic regression was run. RESULTS: The study included 145 patients and 38 (26.21%) developed D2T RA. D2T RA group were older, with more comorbidity and disability. D2T RA patients scored higher for global fatigue (p = 0.003), and almost for all their dimensions except for cognitive fatigue (p = 0.06) and fatigue coping (p = 0.07). Females with D2T RA showed more fatigue than those with non-D2T RA. In the adjusted models, all fatigue dimensions were associated with D2T RA: global fatigue RA (OR: 1.03; p = 0.007), physical (OR: 1.09; p = 0.008), living (OR: 1.09; p = 0.016), cognitive (OR: 1.1; p = 0.046) and emotional (OR: 1.18; p = 0.012). CONCLUSIONS: Despite the absence of an explicit mention of fatigue in the definition of D2T RA, it appears to be associated to this outcome. Fatigue should be evaluated in a multidimensional perspective, and gender-specific differences should be considered.

Incidence and risk factors of discontinuation of tofacitinib and biologic disease-modifying anti-rheumatic drugs among patients with rheumatoid arthritis: A population-based cohort study.

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57-0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation.

Psoriasis management tree based on comorbidity.

Psoriasis, a common chronic inflammatory skin disorder, encompasses various subtypes, including guttate, pustular, erythrodermic, and the most common type, plaque psoriasis. Irrespective of the subtype, psoriasis can manifest with multisystemic presentations, including psoriatic arthritis, metabolic disorders, cardiovascular disease, malignancies, chronic kidney disease (CKD), psychiatric illness, and inflammatory bowel disease (IBD). Many comorbidities and concomitant conditions must be considered when selecting the most appropriate therapy for a patient (Kaushik et al., 2019 and Monks et al., 2021) . Ongoing clinical trials and the development of new therapeutic targets contribute to the continuous improvement of available treatment options. Given the dynamic landscape of therapies, particularly when managing complex patients with multiple comorbidities, dermatologists are constantly challenged with the task of adeptly tailoring treatments to each psoriasis patient. This article systematically reviews the current evidence, presenting it as an updated Psoriasis Decision Tree to assist physicians in selecting tailored treatment options.

Biologicals for the treatment of lupus nephritis: a Bayesian network meta-regression analysis.

Background: Previous studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Moreover, confounding factors such as the duration of follow-up were hardly adjusted in those studies, potentially compromising the results and their extents to clinical settings. Objective: To rigorously investigate the efficacy and safety of biologics in patients with lupus nephritis using Bayesian network meta-regression analyses that adjust for the follow-up period, in order to provide more robust evidence for clinicians. Methods: Databases comprising PubMed, Embase, MedlinePlus, Cochrane Library, Google Scholars, and Scopus were retrieved for eligible articles from inception to February 29, 2024. The primary endpoint was the complete response rate, the secondary endpoint was the partial response rate, the tertiary endpoints were the adverse events, and infection-related adverse events. Napierian Logarithm of hazard ratio (lnHR) and the standard error of lnHR (selnHR) were generated for dichotomous variants by STATA 18.0 MP and then put into Rstudio 4.3.2 to conduct Bayesian network meta-analysis as well as network meta-regression analysis to yield hazard ratio (HR) as pairwise effect size. Results: Ten studies involving 2138 patients and 11 treatment regimens were ultimately included. In the original analysis, for the primary endpoint, compared to the control group, obinutuzumab (22.6 months), abatacept-30mg (20.5 months), abatacept-10mg (17.8 months), and belimumab (23.3 months) demonstrated significant superiority (HR ranged from 1.6 to 2.5), more ever, their significance regarding relative efficacy was correlated with follow up period, namely "time window" (shown in parentheses above). For the secondary endpoint, compared to the control group, obinutuzumab and abatacept-30mg showed conspicuous preponderance (HR ranged from 1.6 to 2.4), "time window" was also detected in abatacept-30mg (20.5 months), whereas obinutuzumab remained consistently obviously effective regardless of the follow-up period (shown in parentheses above). For the tertiary endpoint, there were no differences among active regimens and control. Conclusions: Considering the efficacy and safety and "time window" phenomenon, we recommend obinutuzumab as the preferred treatment for LN. Certainly, more rigorous head-to-head clinical trials are warranted to validate those findings.

Psoriasis and psoriatic arthritis following use of dostarlimab for endometrial cancer.

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), but psoriasis and psoriatic arthritis (PsA) after use of dostarlimab have not been reported. We present a woman who received dostarlimab for endometrial cancer and subsequently developed rash and polyarthralgia, diagnosed as overlapping palmoplantar pustular and plaque psoriasis with PsA. She was treated with discontinuation of dostarlimab, topical steroids, oral methylprednisolone and methotrexate. This case highlights phenotypic heterogeneity in cutaneous irAEs influenced by malignancy and ICI type and underscores the need for multidisciplinary care in treating irAEs. We review three current professional society guidelines for managing irAEs, highlighting their emphasis on management based on severity grading, early initiation of systemic corticosteroids and steroid-sparing agents and discontinuation of ICI for severe events. Certain recommendations deviate from typical approaches to idiopathic rheumatologic disease. Further research is needed to support the ongoing development of approaches to irAE management.

Treatment patterns and factors associated with discontinuation of monoclonal antibodies.

Background: Biological agents have revolutionized care in specialties such as oncology, immunology, infectious diseases, and genetic disorders, offering targeted actions on specific molecules or select immune cells. Monoclonal antibodies, known for their high specificity and precision, represent one of the most significant and rapidly expanding categories of these agents. Understanding the drug utilization patterns of monoclonal antibodies is crucial to ensure their optimal use, especially given their high cost and potential adverse effects. Methods: This analytical cross-sectional study was conducted in a secondary hospital in the United Arab Emirates. Patients of either gender receiving monoclonal antibodies at the study site were included. Treatment patterns, utilization, and factors associated with the discontinuation of monoclonal antibodies were assessed. Results: Hyperlipidemia (136, 39.1%) was the most common indication for monoclonal antibodies, followed by prophylaxis of respiratory syncytial virus infection in congenital heart disease (104, 29.9%) and osteoporosis (42, 12.1%). Evolocumab was the most commonly prescribed monoclonal antibody (135, 38.8%), followed by palivizumab (104, 29.9%), and dupilumab (38, 10.9%). The majority of monoclonal antibodies demonstrated a prescribed daily dose to defined daily dose ratio of 1.0, reflecting their appropriate utilization. One hundred twenty-nine patients (37.0%) discontinued their treatment during the study. Patient's level of education (OR: 0.416, 95% CI: 0.183-0.943, p = 0.036), BMI (OR: 2.358, 95% CI: 1.164-4.777, p = 0.017), number of concomitant medications (OR: 2.457, 95% CI: 1.202-5.025, p = 0.014), and treatment duration (OR: 9.180, 95% CI: 4.909-17.165, p < 0.001) were identified as predictors of discontinuation of monoclonal antibodies. Conclusion: This study represents the first comprehensive investigation in the United Arab Emirates focused on treatment patterns, utilization, and discontinuation of monoclonal antibodies among the local population. Monoclonal antibodies were prescribed for the management of a wide range of clinical conditions. The study reports appropriate utilization of most monoclonal antibodies and identifies factors such as patient education level, BMI, concomitant medications, and treatment duration as independent predictors of monoclonal antibody treatment discontinuation.

Determining the Treatment Strategy for Refractory Ulcerative Colitis Using Prostaglandin E-major Urinary Metabolite (PGE-MUM) Measurement.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a valuable biomarker reflecting the cytokine profile. We encountered a case of a 14-year-old boy with pan-colitis-type ulcerative colitis who was unresponsive to steroids and infliximab. The patient's clinical symptoms gradually deteriorated and surgical treatment was strongly considered because anti-inflammatory therapy was unlikely to be effective. PGE-MUM levels were markedly elevated, indicating a T-helper 17 (Th17)-like cytokine profile. Because an antibody against interleukin 23 (IL-23) was presumed to be effective, the patient was treated with mirikizumab, after which he achieved remission. In the present case, measurement of PGE-MUM levels was useful in selecting anti-cytokine treatments for severe ulcerative colitis.

Patient-reported outcome measures and health economics in regenerative periodontal therapy: A systematic review and meta-analysis.

Understanding patient responses to periodontal regeneration is crucial. This systematic review and meta-analysis addressed two key questions: (a) the impact of periodontal regeneration on patient-reported outcome measures (PROMs) for intrabony and furcation involvement and (b) the cost-effectiveness of periodontal regeneration for treating periodontal defects. Twenty-four studies were included, with 20 randomized clinical trials (RCTs) reporting patient-reported outcomes and five (three RCTs and two economic model-based studies) reporting cost-effectiveness outcomes. Results favored regeneration therapy over conventional flap surgery for intrabony defects, showing improvements in qualitative (i.e., amount of regenerated attachment apparatus) and quantitative parameters (i.e., probing and radiographic parameters). In terms of PROMs, regenerative treatments involving barrier membranes resulted in longer chair times and higher rates of complications (such as membrane exposure or edema) compared to flap with biologic agents or access flap alone. Despite this, oral health-related quality of life improved after both regenerative and extraction procedures. Economically, regeneration remained favorable compared to extraction and replacement or open flap debridement alone for periodontal defects. Single-flap variants in open flap debridement yielded similar outcomes to regenerative treatment, offering a potentially cost-effective option. Nevertheless, further discussion on the benefits of less-invasive flap designs is needed due to the lack of histological evaluation.

The NYMERIA Study: A Real-World, Multicentre Contemporary Assessment of Disease- and Patient-Related Burden and Treatment Strategies in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) has a spectrum of phenotypes. Its management should target remission or low disease activity, prevention of relapses and organ damage, minimisation of drug-related harms, and optimisation of health-related quality of life. Advances in our understanding of the disease pathophysiology have expanded the treatment armamentarium with targeted biologics that demonstrate superiority over conventional drugs in controlling activity, reducing flares and glucocorticoid exposure, and improving patient-related outcomes. In view of this, there is a critical need for real-world evidence providing insight into the spectrum of activity, the treatment landscape, and unmet needs among SLE patients. Such information can support regulatory and reimbursement decision-making. The primary objective of the NYMERIA multicentre study is to generate real-world evidence on the activity state of SLE patients treated in routine care settings in Greece. The overarching aim is to capture the disease burden based on both clinical aspects and the patient perspective.

Treatment selection in the clinical practice of systemic lupus erythematosus: results from the Kyushu Collagen Disease Network for Systemic Lupus Erythematosus (KCDN-SLE) registry.

OBJECTIVES: This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicenter prospective registry in Japan. METHODS: This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated. RESULTS: We analyzed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed. CONCLUSIONS: Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation.

NLRP3 (rs10754558) gene polymorphism and tumor necrosis factor alpha as predictors for disease activity and response to methotrexate and adalimumab in psoriasis.

BACKGROUND: Psoriasis has a global prevalence of 1-3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals. RESULTS: There was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75-7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24-42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001). CONCLUSIONS: The NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.

Acute Motor Conduction Block Neuropathy After Initiation of Omalizumab: Case Report and Literature Review for Possible Causality.

Background: Omalizumab is an established therapy for allergic conditions, yet its neurological effects remain underexplored compared to other biological agents. Case description: A 45-year-old male with asthma developed acute quadriparesis one week after receiving the first dose of omalizumab. Electrophysiological studies have shown partial motor conduction block in multiple nerves, with reduced CMAP amplitudes and absent F-waves in others. CSF showed cyto-albuminous dissociation. The diagnosis was a variant of Guillain-Barré syndrome. Despite intravenous immunoglobulin (IVIG) therapy, the patient experienced persistent neuropathic symptoms. Discussion: The patient presented with acute quadriparesis devoid of sensory or cranial nerve involvement, suggestive of a variant of Guillain-Barré syndrome (GBS) known as acute motor conduction block neuropathy (AMCBN). Electrophysiological studies have indicated conduction block without demyelination, implicating axonal degeneration. Despite negative findings for common etiologies, the temporal association between omalizumab administration and symptom onset suggests a potential link, supported by criteria for drug-induced illness. Conflicting evidence exists regarding omalizumab's neurological effects, with proposed mechanisms including autoimmune reactions and mast cell dysfunction. Comparisons to TNF-α antagonists highlight similar neuropathy patterns, indicating a need for further research to clarify omalizumab's neurotoxicity. Conclusion: In conclusion, while omalizumab holds promise for allergic conditions, including chronic urticaria, its potential impact on peripheral nerves necessitates vigilance among clinicians. Further studies are imperative to ascertain the risk-benefit profile and elucidate underlying mechanisms and risk factors of neurological complications associated with omalizumab therapy.

Very long-term data on patients with severe eosinophilic asthma treated with mepolizumab: a case series.

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab. Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit. Results: Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/µL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p=0.0286). Conclusions: Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term.

The relationship between TNF-α, IL-1, IL-12, IL-17, IL-23, IL-36 expression and treatment response in psoriasis histopathologically and immunohistochemically.

AIM: There is no marker that can predict whether there is resistance to treatment in patients with psoriasis. In this study, we investigated the relationship between the staining rates of TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36 markers immunohistochemically from cutaneous biopsy and the treatment success. METHODS: The patients who were followed up in the dermatology clinic with the diagnosis of plaque-type psoriasis vulgaris and received biological treatment and previously had cutaneous biopsy were included in the study. The cutaneous biopsies of the cases that met the conditions were re-sectioned and subjected to immunohistochemical examination for TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36. RESULTS: Comparing the staining scores with psoriasis area severity index (PASI); A statistically significant positive correlation was found between PASI and TNF-α staining score (p = 0.034). A statistically significant positive correlation was found between PASI and IL-17 staining score (p = 0.004). When the staining scores and PASI response rates of psoriasis treatment were evaluated in terms of correlation; there was a positive correlation between TNF-α, IL-17, and IL-23 immunohistochemical staining rates and PASI response rates. CONCLUSIONS: In line with the data obtained from our study, we think that making immunohistochemical scoring before the biological treatment decision in psoriasis patients will be beneficial in treatment selection. In this respect, our study may open a new era in the selection of biological treatments for psoriasis.

Bibliometric analysis and description of research trends in the treatment of psoriasis with biologic agents in the past two decades (2004-2023).

BACKGROUND: Biologics are essential in treating psoriasis. In recent years, the pathogenesis exploration and development of new target drugs have provided a more complete evidence-based foundation for the biological treatment of psoriasis. This study aims to use bibliometrics to analyze the research status and development trends of biologics in psoriasis. METHODS: The bibliometric analysis of publications related to biologics in psoriasis from 2004 to 2023 was conducted using the Web of Science Core Collection (WoSCC) database as the search data source. To perform the bibliometric analysis and create visual knowledge graphs, CiteSpace, the Bibliometrix R package, and VOSviewers were utilized. RESULTS: The study included a total of 3800 articles. The United States had the highest number of publications. The leading authors and institutions were Steven R. Feldman and the University of Manchester, respectively, in the global partnership. The cluster plot divided all keywords into 11 categories. Currently, Secukinumab and Guselkumab are representative biological agents being studied due to their considerable efficacy and long-term safety. CONCLUSIONS: Targeted therapy has emerged as a significant trend in the current treatment of psoriasis. Early and active use of biologics can effectively control disease progression, prevent or delay the occurrence of comorbidities, and may even alter the natural course of psoriasis. However, further investigation is required to fully understand the specific mechanisms of psoriasis and the use of biological agents.

Case of isolated scleromalacia perforans with seropositivity for rheumatoid arthritis.

Scleromalacia perforans, or necrotising anterior scleritis, is a rare and severe form of eye disease that usually occurs in patients suffering from long-standing systemic inflammatory diseases, with rheumatoid arthritis (RA) being the most common. Here, we report the case of a patient who presented with redness of the eye and discolouration of the sclera and was diagnosed with scleromalacia perforans without any further extraophthalmic systemic involvement. Serological workup revealed highly positive cyclic citrullinated peptide (CCP) antibody (CCP-IgG/anticitrullinated protein antibodies) and positive rheumatoid factor, serologies commonly associated with RA. The patient's symptoms responded very well to rituximab therapy.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

The Impact of Interleukin-17 Inhibitors on Major Adverse Cardiovascular Events in Psoriasis or Psoriatic Arthritis Patients Naive to Biologic Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The objective of this systematic review is to determine the effects of IL-17 inhibitors on major adverse cardiovascular events (MACEs) in patients with either psoriasis (PsO) or psoriatic arthritis (PsA). A systematic literature search in three databases (Medline, Embase, and the Cochrane Library for Randomized Controlled Trials) was conducted on December 7, 2022 for randomized controlled trials of patients with PsO/PsA treated with IL-17 inhibitors that reported confirmed MACEs. Two reviewers screened titles and abstracts and identified papers for full-text review. Exclusion criteria included trials that included the previous use of biological disease-modifying anti-rheumatic drugs. The Mantel-Haenszel random-effect method was utilized to calculate risk ratios and heterogeneity was measured by χ2 test and I2 statistics. Funnel plot analysis was undertaken to detect potential publication bias. Of the 919 references identified, nine RCT studies were included in the meta-analysis (n=2,096 patients). There was no statistically significant correlation between the use of IL-17 inhibitors and change in risk of MACEs (Risk Ratio 0.56; 95% CI 0.15 to 2.14; p = 0.40). Subgroup analysis of secukinumab or ixekizumab also did not demonstrate these changes. Additionally, there was no detectable dose-dependent effect of IL-17 inhibitors. In conclusion, IL-17 inhibitor use is not correlated with a change in MACE risk in patients with PsO/PsA who previously did not receive biologic disease-modifying anti-rheumatic drugs.