Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis.

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

A Propensity Score-Matched Study on the Changes of TB Status and TB-IGRA Values in Patients with Psoriasis with Latent TB Receiving Secukinumab.

INTRODUCTION: The utilization of biologics in patients with psoriasis with latent tuberculosis infection (LTBI) has garnered significant attention. Although the tuberculosis (TB) safety profile of second-generation biologics, including secukinumab, has been partially confirmed in both clinical trials and real-world studies, the necessity for prophylactic therapy in patients with LTBI prior to administering this class of biologics remains a topic of controversy. METHODS: This study enrolled 62 patients with psoriasis with LTBI who underwent secukinumab with routine TB reexamination. Patients were divided into two groups based on whether they received antituberculosis therapy (ATB; n = 48) or not (NTB; n = 16). We performed a propensity score-matched (PSM) analysis between ATB and NTB subgroups and retrospectively reviewed their interferon-gamma release assays (IGRA) and radiographic results. RESULTS: No active TB case was reported on the basis of medical records and chest radiographs in either two group. Before PSM, the mean reexamining IGRA value was significantly elevated in patients who received prophylactic therapy (P = 0.00), but no significant increase was observed in patients who were not. After PSM, there was no significant IGRA value enhancement whether or not patients received prophylactic treatment. CONCLUSION: Our data provide additional information on the safety profile of secukinumab in patients with psoriasis with LTBI. Furthermore, our presentation of the reexamined IGRA results revealed no significant elevation in the ATB or NTB group. As such, we believe further exploration is necessary to determine whether anti-TB medication is required prior to administering secukinumab.

In the past decade, biologics have revolutionized psoriasis treatment. Among patients receiving biologics, tuberculosis infection is a big concern. Secukinumab, an interleukin-17 inhibitor, belongs to the second-generation biologics. Clinical trials and real-life experience have partially reported its tuberculosis safety. In 2020, a systematic review of randomized clinical trials of secukinumab found no reactivate tuberculosis case. However, when participants tested positive for latent tuberculosis infection at screening in the clinical trials, they received antituberculosis treatment. Should patients with latent tuberculosis infection receive antituberculosis medication before receiving secukinumab? The answer is controversial and lacks evidence. This study enrolled patients with psoriasis with latent tuberculosis infection who underwent secukinumab with routine tuberculosis reexamination. Then, the patients were divided into two groups based on whether they received antituberculosis therapy and not. We observed that neither of these two groups presented tuberculosis activation cases. We also matched patients who received antituberculosis therapy and those who did not. The interferon-gamma release assay showed no significant increase after balancing the baseline. Our data indicated that secukinumab is safe among patients with latent tuberculosis infection even when they did not receive antituberculosis treatment.

The Clinical Characteristics of Psoriatic Arthritis: A Cross-Sectional Study Based on the Psoriatic Arthritis Cohort of West China Hospital.

INTRODUCTION: This study aims to describe the demographic, clinical, laboratory, and ultrasonic characteristics of patients with psoriatic arthritis (PsA) in the Psoriatic Arthritis cohort of West China Hospital. METHODS: In this cross-sectional study, we included patients diagnosed with PsA according to the Classification Criteria for Psoriatic Arthritis, collected their demographic information, medical histories, and treatments, evaluated all domains (skin and nail lesions, tenderness, swelling, enthesitis, dactylitis, and axial arthritis) related to PsA, and then performed descriptive statistical analyses of all data. RESULTS: A total of 275 patients with PsA were included in this study. The ratio of male to female patients was 2.16:1. Skin lesions preceded arthritis in 86.5% of these patients with PsA with a mean interval of 10.1 years. The metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints of fingers, and sacroiliac joints are the most commonly involved sites of tenderness, swelling, and the spine, respectively. Among all comorbidities, fatty liver has the highest incidence with 33.1%. Finally, we noted that the mean disease duration of PsA was 4.2 years, suggesting a delay in the diagnosis of PsA. CONCLUSION: Our study proposes that the prevalent population of PsA are male patients with psoriasis over 40 years of age who have a long disease course. For patients with PsA, MCP, PIP joints of fingers, and sacroiliac joints are the most frequently affected anatomical sites. With respect to comorbidities, the association between PsA and fatty liver and the underlying molecular mechanisms are worthy of further exploration.

Efficacy, Safety, and Pharmacoeconomic Analysis of Adalimumab and Secukinumab for Moderate-to-Severe Plaque Psoriasis: A Single-Center, Real-World Study.

INTRODUCTION: A growing number of biologics have recently been approved in China for psoriasis treatment, and some of these are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. Nevertheless, real-world data on the efficacy and safety of biologics for treating moderate-to-severe plaque psoriasis in Chinese patients are limited, and relevant pharmacoeconomic studies are lacking. Therefore, we performed a prospective, single-center study to evaluate the efficacy and safety of adalimumab (ADA) and secukinumab (SEC) in real-world practice. A cost-effectiveness analysis (CEA) was also conducted. METHODS: Participants were enrolled between January 2019 and December 2020 at the West China Hospital, Sichuan University. Baseline and follow-up assessments were conducted, and an appropriate statistical analysis was performed. RESULTS: A total of 183 patients were included. At week 12, the number of patients achieving a psoriasis area and severity index reduction of 75% (PASI 75) with SEC treatment was higher than that with ADA and methotrexate (MTX) (SEC versus ADA versus MTX, 90.59% versus 58.70% versus 17.14%, respectively). Adverse events (AEs) were reported in 44.83% and 56.36% of patients in the SEC and ADA groups, respectively. The cost-effectiveness ratio in the SEC group was 46,311.83 Chinese yuan(CNY), compared with 17,580.92 CNY in the ADA group. CONCLUSION: In real-world practice, SEC and ADA are effective and safe for moderate-to-severe plaque psoriasis treatment in Chinese patients. On the basis of drug prices during our study period without considering access to health insurance, ADA was more cost-effective in real-world practice. Adalimumab and secukinumab are two monoclonal antibodies used for the treatment of psoriasis, which target different cytokines in the pathogenesis. A growing number of biologics have recently been approved in China for psoriasis treatment including adalimumab and secukinumab, which are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. With the purpose of evaluating its efficacy and safety in the real world, we registered the data of eligible patients in West China Hospital, Sichuan University over the past two years and conducted statistical analysis. In order to provide different therapeutic strategies for patients based on case-specific needs and access to financial resources, we performed pharmacoeconomic analyses to evaluate the cost-effectiveness of the two drugs. Our study demonstrated that adalimumab and secukinumab were effective and safe for moderate-to-severe plaque psoriasis in Chinese patients in the real-world practice. Based on drug prices during our study period and without taking into consideration access to health insurance, ADA was more cost-effective in real-world practice.

The Tuberculosis Positive Conversion Rate Among Psoriasis Patients Treated with Adalimumab and Secukinumab: A Single-Center Retrospective Study in China.

INTRODUCTION: The tuberculosis (TB) positive conversion rate among psoriasis patients who received biologics has been reported worldwide, particularly in regions with low TB risk. Nonetheless, the TB-related safety of biologics such as adalimumab and secukinumab remains elusive in areas with high TB risk. According to the World Tuberculosis Report 2021, China is the country with the second highest TB burden, but data on TB conversion are also limited. Thus, we performed a retrospective, single-center study to profile the TB infection status conversion ratio among psoriasis patients treated with adalimumab and secukinumab in China. METHODS: Patients were enrolled between April 2019 and February 2021 from West China Hospital, Sichuan University. Baseline and relevant clinical information were summarized, and proper statistical analysis was used under different conditions. RESULTS: Five (5.43%) patients suffered TB conversion in the adalimumab group, two of whom developed active TB within the first 6 months. In the secukinumab group, four (5.26%) patients had TB positive conversion with no reports of active TB. CONCLUSION: Our data show a relatively high rate of TB conversion among these psoriasis patients after mean treatment duration of 17.13 months. We recommend that, in patients who receive adalimumab, TB be reevaluated after the first 3 months and then monitored semiannually for the next 2 years. For patients treated with secukinumab, annual examination is sufficient.

Effect of NUDT15 polymorphisms on early hematological safety of low-dose azathioprine in Chinese patients with pemphigus vulgaris: A prospective cohort study.

Azathioprine (AZA) is the preferred immunosuppressant for treating pemphigus vulgaris (PV), with discontinuation mainly attributed to hematological adverse events (AE). Reportedly, nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) polymorphisms have been strongly associated with thiopurine-induced leukopenia. To investigate hematological AE of low-dose AZA based on NUDT15 genotypes among patients with PV, a prospective cohort study was conducted in patients with PV, followed-up for the first 8 weeks after AZA administration. All patients were divided into wild homozygous and heterozygous NUDT15 groups. Both groups initiated AZA at low dose (50 mg/day) and continued with different dose-escalating approaches. Bone marrow suppression was considered the principal outcome. Overall, 62 patients with PV were enrolled (48 in the wild homozygous NUDT15 group vs. 14 in the heterozygous NUDT15 group). Except for median maintenance doses of AZA, no statistically significant differences were observed between the two groups in terms of age, sex, white blood cells, neutrophil count, platelet count, hemoglobin level, median final doses of corticosteroids (mg prednisone equivalent), pemphigus disease area index, and anti-desmoglein 1/3 autoantibodies. In both groups, patients presented similar hematological AE and treatment responses after administration of different low-dose AZA treatment strategies. Low-dose AZA based on NUDT15 genotypes can reduce the risk of early hematological AE among patients with PV.

Development of a Predictive Model for Screening Patients with Psoriasis at Increased Risk of Psoriatic Arthritis.

INTRODUCTION: This study aimed to develop a predictive model based on ultrasound variables which can be used to screen patients with psoriasis who are prone to progress to psoriatic arthritis (PsA) in clinical practice. METHODS: This is a cross-sectional study conducted in a single center from October 2018 to November 2020. All subjects (non-PsA group, PsA group, and control group) underwent an ultrasound examination and their ultrasound abnormalities were recorded. On the basis of statistical analysis and clinical experts' advice, several variables were selected for modelling. We used logistic regression to establish the prediction model. To assess the discrimination and accuracy of this model, internal validation and external validation were performed. RESULTS: A total of 852 patients with psoriasis but without PsA, 261 patients with PsA, and 86 healthy volunteers were included. Ultimately, the predictive model consisted of six variables, namely hand joint power Doppler (PD) signals (grade 0: OR 2.94, 95% CI 1.94-4.47; grade ≥ 1: OR 109.30, 95% CI 14.35-832.27; P < 0.001), wrist joint synovial thickening (grade 1: OR 1.29, 95% CI 0.69-2.43; grade 2: OR 4.30, 95% CI 1.92-9.65; grade 3: OR 11.05, 95% CI 1.01-120.64; P = 0.001), knee joint PD signals (grade 0: OR 1.01, 95% CI 0.56-1.80; grade ≥ 1: OR 14.77, 95% CI 3.99-54.69; P < 0.001), toe joint PD signals (grade 0: OR 1.18, 95% CI 0.78-1.79; grade ≥ 1: OR 5.74, 95% CI 2.84-11.63; P < 0.001), quadriceps tendon and patellar tendon enthesitis (OR 1.95, 95% CI 1.36-2.78, P < 0.001), Achilles tendon and plantar aponeurosis enthesitis (OR 1.63, 95% CI 1.14-2.32, P = 0.007). C-index for the predictive model was 0.80 (95% CI 0.76-0.83). After bootstrapping validation (1000 times), it was confirmed to be 0.79. The external validation showed the accuracy of the predictive model is 0.87 (95% CI 0.69-0.95). CONCLUSION: This study succeeded in developing a predictive model with a high degree of accuracy to predict the risk of PsA in patients with psoriasis.

Psoriatic arthritis often occurs in the population of patients with psoriasis. It brings a huge burden and pain to patients. At present, the diagnosis for psoriatic arthritis is very challenging. Numerous research studies have begun to focus on identifying patients with psoriasis at increased risk of psoriatic arthritis. Among a lot of modalities, ultrasound has been considered as a sensitive and convenient tool for screening early psoriatic arthritis. Our study successfully established a predictive model based on ultrasound variables to screen patients with psoriasis at high risk of transiting to psoriatic arthritis. After internal and external validation, it showed great accuracy and generalizability. We recommend that clinicians perform ultrasound screening of patients with psoriasis in clinical routine and get their risk value of transiting to psoriatic arthritis by using this model. For those patients with a high risk of progression to psoriatic arthritis, clinicians should refer them to a rheumatology department as soon as possible so that they could have access to early and effective management which might bring them good clinical and imaging outcomes.

Risk Factors for Progression from Subclinical to Clinical Phase of Psoriatic Arthritis: A Case-Control Study.

INTRODUCTION: The objective of this study is to identify the potential risk factors for progression from subclinical to clinical psoriatic arthritis (PsA). METHODS: A retrospective, longitudinal, case-control study was conducted at a single hospital, including 25 patients with clinically confirmed PsA in the case group and 137 controls without confirmed PsA. All patients in both groups had a medical history of subclinical PsA. Various baseline covariates were collected from all patients when they had a status of subclinical PsA. Univariate, multivariate, stratified, and interaction analyses were employed to identify potential risk factors of transiting to clinical PsA from subclinical PsA. RESULTS: In multivariate logistic regression analysis, older age (OR 10.15, 95% CI 2.79-36.91, p = 0.00), alcohol drinking (OR 3.43, 95% CI 1.17-10.12, p = 0.03), elevated high-sensitivity C-reactive protein (hs-CRP) (OR 1.05, 95% CI 1.01-1.09, p = 0.03) were identified as risk factors for transition from subclinical to clinical PsA. Stratified and logistic regression analyses suggest a significant interaction between age and fatty liver. For patients aged less than 45 years old, the association between fatty liver and clinical PsA was statistically significant. CONCLUSIONS: Older age, alcohol drinking, elevated hs-CRP, and the presence of fatty liver at less than 45 years old appear to increase the risk of transition from subclinical to clinical PsA. These findings call for a need to manage these risk factors.