An Evaluation of Skin and Immunological Responses after Using a Novel Cross-Linked Porcine-Based Dermal Injectable Collagen with Lidocaine for Nasolabial Fold Correction.

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing.

Predicting the Time to Relapse Following Withdrawal from Different Biologics in Patients with Psoriasis who Responded to Therapy: A 12-Year Multicenter Cohort Study.

BACKGROUND: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. OBJECTIVE: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. METHODS: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model. RESULTS: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. CONCLUSIONS: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases.

Clinical Characteristics and Disease Burden of Patients with Moderate-to-Severe Generalized Pustular Psoriasis Flares in Taiwan.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. METHODS: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008-December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. RESULTS: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87-61.78), 14.08 (95% CI 3.04-65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08-0.54) and 0.07 (95% CI 0.006-0.78), respectively. CONCLUSIONS: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes.

Evaluation of Collagen Dermal Filler with Lidocaine for the Correction of Nasolabial Folds: A Randomized, Double-Blind, Multicenter Clinical Trial.

Purpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection. Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05). Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.

Small-Molecule Inhibitors and Biologics for Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. OBJECTIVE: The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks. RESULTS: The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome. CONCLUSION: Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.

Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials.

Background: Infection events are a major concern for patients and physicians when making psoriasis treatment decisions. Objective: To estimate the relative short-term risks of infection and serious infection for biologic and small molecule therapies in the treatment of moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA). Data Sources and Methods: A systematic literature search of the PubMed, EMBASE, and Web of Science databases was conducted on 17 June 2022. We included phase II, III, or IV randomized controlled trials (RCTs) of biologic and small-molecule therapies that are licensed or likely to gain approval soon for PsO and PsA, as well as infection data reports. Two investigators independently extracted the data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis (NMA) was performed to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals of total infections and serious infections for treatments during placebo-controlled phases of RCTs. The surface under the cumulative ranking area (SUCRA) was calculated to rank the infection risk for each treatment. Results: A total of 94 RCTs with a total of 19 treatment arms involving 54,369 participants were analyzed. For patients with PsO, bimekizumab, secukizumab, risankizumab, ustekinumab, apremilast, guselkumab, and adalimumab were associated with significantly higher risks of infection than placebo; SUCRA ranked infliximab, deucravacitinib, and bimekizumab with the highest risks of infection. For patients with PsA, bimekizumab, apremilast, and upadacitinib (30 mg daily) were associated with higher risks of infection; SUCRA ranked bimekizumab with the highest risk of infection. No treatments, except for upadacitinib (30 mg daily), were associated with a higher risk of serious infection than placebo in PsA. Conclusion: This NMA provides a comprehensive assessment of the comparative short-term risks of infection, which could help physicians and patients to select individualized treatments for psoriasis. Registration: CRD42022359873.

Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2.

INTRODUCTION: Guselkumab is a human monoclonal antibody against IL-23 used in the treatment of moderate-to-severe psoriasis. This post-hoc analysis evaluated the efficacy and safety of guselkumab in the Asian subpopulation of VOYAGE 1 and VOYAGE 2 through 5 years. METHODS: The proportions of guselkumab-treated Asian patients (VOYAGE 1 and 2) achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100, Investigator's Global Assessment (IGA) scores of 0/1 and 0, and Dermatology Life Quality Index (DLQI) scores of 0/1 (week 100 through week 252) were assessed. Non-responders were patients who met the treatment failure rules. Efficacy endpoints were analyzed using the as-observed methodology (no missing data imputation) for both studies and using non-responder imputation (for patients with any missing data) in VOYAGE 1. Safety outcomes were based on pooled data through week 252. RESULTS: Response rates through week 252 for 199 Asian patients in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 76.8% and 80.6% (PASI 90), 26.8% and 38.7% (PASI 100), 64.3% and 87.1% (IGA 0/1), and 26.8% and 45.2% (IGA 0). DLQI (0/1) at week 252 was achieved by 52.7% of patients in VOYAGE 1 and 61.3% in VOYAGE 2, while DLQI (0) at week 252 was achieved by 32.7% of patients in VOYAGE 1 and 40.3% in VOYAGE 2. The safety profile was similar to the global population and remained consistent through 5 years. Asian patients were followed for a total of 814 patient-years (PY). Over 85% of the guselkumab-treated patients continued treatment through week 264. The rate of serious adverse events (AEs) at week 252 was 3.07/100 PY. Rates of AEs of interest were low: serious infections, 0.74/100 PY; nonmelanoma skin cancer (NMSC), no patients; malignancies other than NMSC, 0.12/100 PY; and no major adverse cardiovascular events (MACE). CONCLUSION: These analyses confirm a continuous response over 5 years, indicating that guselkumab shows therapeutic longevity in Asian patients requiring long-term treatment for moderate-to-severe psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: VOYAGE 1 [NCT02207231] and VOYAGE 2 [NCT02207244].

Psoriasis­a long-term condition that causes a skin rash with scaly, itchy patches (plaques)­is becoming more prevalent in Asia. To control symptoms of moderate-to-severe psoriasis and achieve a strong improvement in the patient's quality of life, continuous treatment is usually needed. Guselkumab is a medicine that targets specific parts of the immune system to treat moderate-to-severe psoriasis. It is important to understand the long-term benefits of guselkumab in Asian patient populations. Our study analyzed the data from two randomized clinical trials (called VOYAGE 1 and VOYAGE 2) that studied people with moderate-to-severe plaque psoriasis. We examined results for the 199 people from Asia, including Korea and Taiwan, who took part in these studies. Overall, 162 of the 184 (86.6%) people from Asia treated with guselkumab incorporated into these studies continued the treatment for 5 years. Patients treated with guselkumab showed effective clinical responses (improvements measured by clinicians), including high skin clearance, meaning a large reduction in skin surface area affected by psoriasis. On guselkumab, patients also reported improvements in their skin-related health-related quality of life. These improvements and the efficacy of guselkumab were maintained over 5 years of follow-up. The safety results for guselkumab in the Asian subpopulation were similar to those for the global population, showing low rates of serious adverse effects, as expected from this type of medicine. Overall, our study found a favorable benefit­risk profile with continuous guselkumab treatment for 5 years in Asian people with moderate-to-severe psoriasis. This highlights that guselkumab treatment allows long-lasting control of this disease.

Efficacy of guselkumab in difficult-to-treat psoriasis regions: Data from VOYAGE 1 and VOYAGE 2 Asian subpopulations.

Patients with psoriasis were randomized to guselkumab, placebo or adalimumab in the VOYAGE 1 and VOYAGE 2 studies. In this post hoc analysis, difficult-to-treat psoriasis regions in the Asian subpopulation for both the guselkumab and adalimumab groups were compared with placebo at week 16 and the active treatment groups were compared at week 24. Endpoints included patients achieving scores of 0 or 1 (clear or near clear) or 0 (clear) on the scalp-specific Investigator's Global Assessment (ss-IGA), Physician's Global Assessment of the hands and/or feet (hf-PGA), and fingernail PGA (f-PGA), and percentage improvement in target Nail Psoriasis Severity Index (NAPSI) score through week 24. Efficacy was also assessed by prior biologic experience at baseline. A total of 199 eligible Asian patients were included. The proportion of patients achieving "clear" or "near clear" with guselkumab was superior to adalimumab at week 24 for scalp psoriasis ss-IGA (Asian patients, 72 [85.7%] vs 35 [67.3%], P = 0.004), hands and/or feet psoriasis hf-PGA (29 [82.9%] vs 16 [61.5%], P = 0.054), and similar for fingernail psoriasis f-PGA (28 [63.6%] vs 17 [54.8%], P = 0.412). Guselkumab mean improvements in NAPSI were comparable to adalimumab (39.9% vs 35.9%, P = 0.618). Overall, the complete clearance response of scalp, and hands and/or feet at week 24 occurred in a greater proportion of patients in the guselkumab group, irrespective of baseline biologic status (treatment-naïve or treatment-experienced). Guselkumab was superior to adalimumab for the treatment of scalp, and hands and/or feet psoriasis, and proportionally higher for fingernail psoriasis. Findings were comparable to the global study population.

The effect of paternal psoriasis on neonatal outcomes: a nationwide population-based study.

Background: Psoriasis is a chronic autoimmune disease involving both environmental and genetic risk factors. Maternal psoriasis often results in poor pregnancies that influence both mothers and newborns. However, the influence of paternal psoriasis on the newborn remains unknown. The aim of this study was to investigate whether paternal psoriasis is associated with increased risk of adverse neonatal outcomes, within a nationwide population-based data setting. Methods: Singleton pregnancies were identified in the Taiwan National Health Insurance database and National Birth Registry between 2004-2011 and classified into four study groups according to whether mothers and spouses had psoriasis (paternal(-)/maternal(-), paternal(+)/maternal(-), paternal(-)/maternal(+), and paternal(+)/maternal(+)). Data were analyzed retrospectively. Adjusted odds ratios (aOR) or hazard ratios (aHR) were calculated to evaluate the risk of neonatal outcomes between groups. Results: A total of 1,498,892 singleton pregnancies were recruited. Newborns of fathers with psoriasis but not of mothers with psoriasis were associated with an aHR (95% CI) of 3.69 (1.65-8.26) for psoriasis, 1.13 (1.06-1.21) for atopic dermatitis and 1.05 (1.01-1.10) for allergic rhinitis. Newborns of mothers with psoriasis but not of fathers with psoriasis were associated with an aOR (95% CI) of 1.26 (1.12-1.43) for low birth weight (<2500 g) and 1.64 (1.10-2.43) for low Apgar scores, and an aHR of 5.70 (2.71-11.99) for psoriasis. Conclusion: Newborns of fathers with psoriasis are associated with significantly higher risk of developing atopic dermatitis, allergic rhinitis and psoriasis. Caution is advised for adverse neonatal outcomes when either or both parents have psoriasis.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Compositional Alteration of Gut Microbiota in Psoriasis Treated with IL-23 and IL-17 Inhibitors.

Alterations in the gut microbiota composition and their associated metabolic dysfunction exist in psoriasis. However, the impact of biologics on shaping gut microbiota is not well known. This study aimed to determine the association of gut microorganisms and microbiome-encoded metabolic pathways with the treatment in patients with psoriasis. A total of 48 patients with psoriasis, including 30 cases who received an IL-23 inhibitor (guselkumab) and 18 cases who received an IL-17 inhibitor (secukinumab or ixekizumab) were recruited. Longitudinal profiles of the gut microbiome were conducted by using 16S rRNA gene sequencing. The gut microbial compositions dynamically changed in psoriatic patients during a 24-week treatment. The relative abundance of individual taxa altered differently between patients receiving the IL-23 inhibitor and those receiving the IL-17 inhibitor. Functional prediction of the gut microbiome revealed microbial genes related to metabolism involving the biosynthesis of antibiotics and amino acids were differentially enriched between responders and non-responders receiving IL-17 inhibitors, as the abundance of the taurine and hypotaurine pathway was found to be augmented in responders treated with the IL-23 inhibitor. Our analyses showed a longitudinal shift in the gut microbiota in psoriatic patients after treatment. These taxonomic signatures and functional alterations of the gut microbiome could serve as potential biomarkers for the response to biologics treatment in psoriasis.

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

2022 Taiwanese Dermatological Association (TDA), Taiwanese Association for Psoriasis and Skin Immunology (TAPSI), and Taiwan Society of cardiology (TSOC) joint consensus recommendations for the management of psoriatic disease with attention to cardiovascular comorbidities.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug-drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

Ultrasound Can Be Usefully Integrated with the Clinical Assessment of Nail and Enthesis Involvement in Psoriasis and Psoriatic Arthritis.

Objectives: This study aimed to examine and compare the findings of nail and enthesis ultrasonography in patients with psoriasis and psoriatic arthritis. Methods: We identified 154 patients with psoriatic arthritis and 35 patients with psoriasis who were treated at Chang Gung Memorial Hospital, Taiwan, between September 2018 and January 2019. Results: There were significant differences in the Nail Psoriasis Severity Index scores and Glasgow Ultrasound Enthesitis Scoring System scores between patients with psoriasis and those with psoriatic arthritis. B-mode ultrasonography revealed that onychopathic changes were more common in the psoriasis group. The psoriatic arthritis group showed a higher proportion of lower-limb enthesopathy, with significant differences in distal patellar ligament thickness and Achilles tendon thickness. Conclusion: The findings of nail ultrasonography were more severe in psoriasis cases, and the ultrasonographic findings of enthesopathy of the lower limb were more severe in cases of psoriatic arthritis.

Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Implementation of NUDT15 Genotyping to Prevent Azathioprine-Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10-25 , odds ratio (OR) = 21.7, 95% confidence interval (95% CI) = 12.1-38.8) and NUDT15 rs746071566 (P = 4.2 × 10-9 , OR = 7.1, 95% CI = 3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate = from 7.6% decreased to 0.4%; P = 9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

Persistence and Adherence to Biologics in Patients with Psoriasis in Taiwan: A New Biologics User Cohort Study.

Background: Biologics are used to treat moderate-to-severe psoriasis, and persistence to biologics may reflect clinical effectiveness. Limited information describing how biologics are used in patients with moderate-to-severe psoriasis in Asian countries is available. We conducted a population-based, retrospective, new user cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan to assess treatment persistence and adherence to biologics. Methods: Adults with a diagnosis of psoriasis between 01 January 2015 and 31 December 2017 were identified in the NHIRD (ICD-9-CM 696.1; ICD-10 L40.0). New users were patients who initiated treatment with etanercept, adalimumab, ustekinumab or secukinumab between 01 January 2015 and 31 December 2017. All eligible patients were followed until 31 December 2018, death or disenrollment. Kaplan-Meier analysis was conducted to estimate persistence of treatment for index biologics. A Cox-proportional hazard regression model was used to compare risks of biologic discontinuation between biologic groups. Adjustments for potential confounding factors (age, gender and Charlson comorbidity index score) were made in the Cox model. Results: There were 1,397 new biologic users with psoriasis during the study period. The ratio men:women was approximately 4:1. Mean age of patients ranged from 44.6 to 47.7 years across exposure groups. The 1-year/2-years persistence rates were 94.2%/84.9% for ustekinumab, 96.2%/not calculated (due to too few patients at year 2) for secukinumab, 66.0%/29.9% for etanercept, and 59.8%/40.3% for adalimumab. The risk of discontinuation was significantly lower in patients initiating ustekinumab compared with adalimumab (hazard ratio adjusted for age, sex and co-morbidities 0.289, 95%CI 0.247-0.339, p < 0.0001). Drug survival was significantly higher for ustekinumab compared with adalimumab and etanercept (log-rank test p < 0.0001). The proportions of patients with 1-year/2-years medication possession ratios of ≥80% were 95.3%/92.0% for ustekinumab, 98.1%/not calculated for secukinumab, 89.4%/83.1% for etanercept, and 70.8%/59.4% for adalimumab. Limitations: Clinical improvement and response to treatment data were not available. Conclusion: There was relatively high persistence amongst biologic users with psoriasis in Taiwan. There is a trend towards greater persistence of ustekinumab compared to other biologics, the magnitude of which depends on the treatment gap used for its calculation. This study provides real-world evidence that may facilitate optimal treatment choice.