Superior effect of adalimumab versus secukinumab on ultrasound-confirmed synovitis in psoriatic arthritis: comprehensive evidence from musculoskeletal ultrasound and clinical assessments.

Background and objectives: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder affecting 30% of psoriatic patients. Effective treatment, especially with biologics like IL-17 and TNF inhibitors, is vital for improving patient outcomes. This study aimed to compare the efficacy of secukinumab and adalimumab in PsA patients through clinical and ultrasonographic evaluations.Materials and methods: We enrolled 116 PsA patients, with 58 patients receiving secukinumab and 58 receiving adalimumab. Regular follow-ups were conducted at weeks 4, 12, 24, and 52. The primary outcome was the proportion of patients achieving at least a 20% improvement in the ACR response (ACR20) at week 12, with additional evaluations for axial arthritis, enthesitis, skin involvement, minimal disease activity, health assessment questionnaire, and ultrasound changes.Results: There was no significant difference in ACR20 response between the two groups at week 12 (OR: 0.59, 95% CI: 0.26-1.37, p = 0.22). However, secukinumab demonstrated superior efficacy in achieving Psoriasis Area and Severity Index (PASI)90 (OR: 2.25, 95%CI: 1.07-4.74, p = 0.03), while adalimumab showed better improvement in ultrasound synovitis count (ß: 0.94, 95%CI: 0.09-1.79, p = 0.03) and synovitis PD signal (ß: 0.20, 95%CI: 0.03-0.36, p = 0.02).Conclusions: In conclusion, both treatments were highly effective for PsA, with secukinumab being more suitable for severe skin involvement and adalimumab for significant ultrasound-confirmed synovitis.

2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore.

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermato-logical Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticoste-roids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combina-tion or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

Neuropathic pain in spondyloarthritis: Decoding its prevalence, risk factors, and impact on disease activity.

OBJECTIVES: This study aimed to evaluate the prevalence and characteristics of neuropathic pain in patients with various subtypes of spondyloarthritis (SpA), including axial SpA (axSpA), psoriatic arthritis (PsA), and undifferentiated peripheral SpA (p-SpA). Additionally, the study sought to identify potential risk factors associated with the presence or severity of neuropathic pain and to investigate its impact on clinical disease activity assessment. METHODS: We conducted a cross-sectional study at two tertiary rheumatology centers, enrolling patients diagnosed with SpA. Data on demographic and clinical characteristics, comorbidities, and current therapies were collected. Neuropathic pain was assessed using the PainDETECT Questionnaire (PD-Q) and the Neuropathic Pain Symptom Inventory (NPSI). Statistical analyses included descriptive statistics, t-tests, and Pearson's correlations to evaluate the relationships between neuropathic pain scores and clinical disease activity indices. RESULTS: The study included 177 patients. Of these, 22.2% had a PD-Q score ≥19, showing a high likelihood of neuropathic pain, while 64.9% scored ≤12, suggesting the absence of significant neuropathic components. The mean PD-Q score was 11.5 ± 10.1. Subgroup analyses showed that females had significantly higher scores for paroxysmal and evoked pain (p < 0.05), and obese patients had significantly higher scores across all NPSI subscores (p < 0.05). Moderate positive correlations were found between neuropathic pain scores and clinical disease activity indices, such as DAPSA (r = 0.46, p < 0.0001) and ASDAS-CRP (r = 0.42, p < 0.01). CONCLUSIONS: Neuropathic pain is prevalent among patients with SpA and is significantly associated with disease activity assessments and management. This study highlights the importance of integrating neuropathic pain evaluation into the clinical assessment of SpA to tailor treatment approaches effectively and improve patient outcomes.

Utility of multi-biomarker panel on discriminating disease activity in patients with psoriatic arthritis.

OBJECTIVE: To investigate the correlation of serum protein biomarkers and disease activity in patients with PsA. METHODS: 176 patients fulfilled the CASPAR (ClASsification criteria for Psoriatic ARthritis) were recruited in this cross-sectional study. The level of 48 protein biomarkers, cartilage and bone turn-over markers were assessed. The patients were randomly divided into a derivation-cohort and a validation-cohort at a ratio of 7:3. Patients were further categorized based on their disease activity states using cDAPSA (remission/low disease activity and moderate/high disease activity). Least absolute shrinkage and selection operator (LASSO) was used to select biomarkers which were associated with moderate/high disease activity in the derivation cohort. Receiver operating characteristic (ROC) curve, GiViTI calibration belt were used to assess the performance of the model in both cohorts. RESULTS: The cohort [age: 55.5 (44.0-62.75) years, male: 80 (45.5 %)] had moderate disease activity [DAPSA: 15.9 (8.3-26.9); PASI: 3.2 (0.5-6.8)]. 101 PsA patients (57.4 %) had clinical DAPSA moderate/high disease activity. Biomarker levels associated with moderate/high disease activity included SAA (Serum amyloid A), IL-8 (Interleukin 8), IP10 (Interferon gamma-induced protein 10)/CXCL10, M-CSF (Macrophage colony-stimulating factor), SCGF-ß (Stem cell growth factor), SDF-1α (Stromal cell-derived factor 1α)/CXCL12. The model's equation including the 6 biomarker levels was applied to the validation-cohort. The area under the ROC curve (AUC) for discriminating moderate/high disease activity was 0.802 and 0.835 for the derivation-and-validation-cohorts, respectively. The multi-biomarkers panel model had higher-AUC when compared with that of C-reactive protein (CRP) (AUC = 0.727, p = 0.022). The P-values of calibration charts in the two sets were 0.902 and 0.123. CONCLUSIONS: The multi-biomarkers panel demonstrated the ability to discriminate patients with moderate/high disease activity from those with low disease activity/remission.

Tofacitinib treatment for plaque psoriasis and psoriatic arthritis: A meta-analysis of randomised controlled trials.

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

High-frequency ultrasonography for the detection of subclinical arthritis in chronic plaque psoriasis patients - A cross-sectional study.

Background Psoriatic arthritis (PsA) is seen in almost 30-40% cases of psoriasis. Psoriasis precedes the onset of PsA in 85% of cases. Delay in the diagnosis of PsA may lead to poor functional outcomes and morbidity. Screening psoriasis patients with high-frequency ultrasound helps to diagnose arthritis at an early stage leading to prompt intervention and possible reduction in the morbidity associated with the disease. Objectives To determine the role of high frequency ultrasonography (USG) in the detection of subclinical PsA. Methods A cross-sectional study was conducted in a dermatology and radiology department of Armed Forces Medical College, Pune between July 2021 and December 2022. Patients of chronic plaque psoriasis with no clinical evidence of arthritis were assessed using high-frequency USG. Various parameters such as bony erosions, synovial thickening, tendon thickening, tendon hypo-echogenicity, calcifications and power doppler signals were assessed. Results A total of 117 patients were included in the study. The distal interphalangeal joint (DIP) and Achilles tendon were the most commonly affected sites. Synovial thickening in DIP was observed in 67 (57%) patients and Achilles tendon thickening was observed in 39 (33%) patients. Limitations of the study The cross-sectional nature of the study is the major limitation. A longitudinal study will be required to understand the clinical relevance of ultrasonographic changes in these patients. Another limitation of the study is the lack of age and gender-matched controls. Future research should include such controls to ensure more accurate results. Conclusion Subclinical arthritis is common in patients with chronic plaque psoriasis. High-frequency ultrasound is a useful tool for detecting subclinical synovitis and enthesitis in asymptomatic patients. The DIP joint and Achilles tendon ultrasound can be used for screening for early detection of PsA.

Feasibility test of WORK-ON: a vocational rehabilitation intervention for people with chronic inflammatory arthritis.

BACKGROUND: People with chronic inflammatory arthritis (IA) often have a reduced work ability. Consequently, they are at high risk of losing their jobs and being permanently excluded from the labor market. Therefore, we developed a new context-specific vocational rehabilitation intervention for people with IA based on the Medical Research Council's framework for complex interventions. This intervention is called "WORK-ON" and consists of: (1) Initial assessment and goal setting by an occupational therapist experienced in rheumatology rehabilitation; (2) coordinated support from the same occupational therapist, including assistance in navigating the primary and secondary healthcare and social care systems; (3) group sessions for peer support; and (4) individually tailored consultations with physiotherapists, nurses, and/or social workers. This study investigates the feasibility of WORK-ON. METHODS: A 6-month single-arm feasibility study with a pre-test post-test design was conducted to evaluate recruitment, intervention fidelity and delivery, data collection, and possible outcome measures. Work ability was the primary outcome, and sick leave, quality of life, fatigue, pain, physical activity, sleep, and well-being were the secondary outcomes evaluated. RESULTS: In total, 19 participants (17 women and 2 men) with a median age of 55 years (range, 34-64) participated and completed WORK-ON. Of these, 17 participants completed patient-reported outcomes at baseline and follow-up, and the results indicated a tendency to improvement in work ability, quality of life, level of physical activity, decrease in pain, and increase in days of sick leave during the 6-month intervention period. The rehabilitation clinicians spent an average of 15.3 h per participant, and the participants spent an average of 13.5 h in the intervention. CONCLUSIONS: WORK-ON is considered feasible and has the potential to increase work ability among people with IA who are concerned about their future ability to keep working. Though, an adjustment of the intervention is needed before testing in a randomized controlled trial.

Successful treatment of the dupilumab-induced psoriatic dermatitis/arthritis and atopic dermatitis with a JAK inhibitor: A case report and literature review.

Dupilumab-induced psoriatic dermatitis and arthritis in a patient with atopic dermatitis were effectively managed with upadacitinib, highlighting the use of Janus kinase inhibitors as a possible treatment for biologic therapy side effects.

Predicting Psoriatic Arthritis in Psoriasis Patients - A Swiss Registry Study.

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P = .01). Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

Assessing Comparative Efficacy of Biologics for the Treatment of Psoriasis With Nail Involvement: A Systematic Review.

Background: Despite recent advances in biologics, there is a lack of significant evidence regarding the comparative efficacy of biologics in treating more resistant features of psoriasis, namely nail psoriasis. A systematic review synthesizing data from multiple studies is efficacious in assessing the comparative efficacy among biologics for the treatment of nail psoriasis. Objective: To evaluate and compare the efficacy of biologics for the treatment of nail psoriasis. Methods: Utilizing PRISMA guidelines, a systematic literature review was conducted using the Pubmed database on November 16, 2022. Studies selected were phase 3 or 4 randomized clinical trials, clinical studies, or other randomized trials with data on the treatment with biologics for adults with nail psoriasis. Results: Sixteen studies meeting inclusion criteria were included for analysis. At 24 weeks, the highest mean NAPSI percent improvement achieved at week 24 was by brodalumab (76.9%) followed by etanercept (74%) and ixekizumab (70.5%) while the biologics achieving the greatest proportion of NAPSI 0 were adalimumab (44.6%) and ixekizumab (41%). Conclusions: This study helps elucidate the comparative efficacy of biologics for the treatment of nail psoriasis. This review suggests that brodalumab and etanercept are associated with the highest percent improvement in nail psoriasis while adalimumab and ixekizumab are associated with the greatest probability of complete nail resolution.

Switching related to inefficacy in biologics and targeted synthetic therapies for psoriatic arthritis: a comparative real-life study.

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce. Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups. Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic. Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI. Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51-13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17-4.36); others vs TNFi: 3.21 (1.59-6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine. Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy.

METHODS: We included patients from 2007 to 2022 in which their consultant rheumatologist had decided to commence them on biologic therapy. We studied the changes due to drug failure, we also included sociodemographic, clinical and treatments information. RESULTS: The study comprised 141 patients. 52% were women in their fifties. We found that 56 patients change drugs 121 times, with 103 of those changes due to failure drug. This means about 11 out of every 100 patients change their biologic therapy each year. There was no difference in the risk of change between the different studied biologic therapies. Women, those with inflammatory back pain, and those who had tried many different drugs were more likely to change due to drug failure. Using additional therapies like glucocorticoids and sulfasalazine also increased the probability of biologic therapy change. CONCLUSION: Our work did not find differences in the risk of change due to drug failure among different biologic therapies.

Changes due to drug failure between biologic therapies: a real-life study in psoriatic arthritis patients Introduction: We wanted to evaluate how often patients with psoriatic arthritis change between different drugs because the drugs weren't working well enough. Additionally, we evaluated which factors could influence the change due to drug failure. The studied drugs are biological therapies that are arthritis-modifying drugs designed early in the last decade to prevent or reduce inflammation caused by the disease.

A review of the advances in understanding the genetic basis of spondylarthritis and emerging clinical benefit.

Spondyloarthropathies (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have been shown to have a substantial genetic predisposition based on heritability estimates derived from family studies and genome-wide association studies (GWAS). GWAS have uncovered numerous genetic loci associated with susceptibility to SpA, with significant associations to human leukocyte antigen (HLA) genes, which are major genetic risk factors for both AS and PsA. Specific loci differentiating PsA from cutaneous-only psoriasis have been identified, though these remain limited. Further research with larger sample sizes is necessary to identify more PsA-specific genetic markers. Current research focuses on translating these genetic insights into clinical applications. For example, polygenic risk scores are showing promise for the classification of disease risk and diagnosis and future research should focus on refining these risk assessment tools to improve clinical outcomes for individuals with SpA. Addressing these challenges will help integrate genetic testing into patients care and impact clinical practice.

Bridging the Diagnostic Gap for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: Evidence of a Common Extracellular Matrix Fragmentation Pattern in Patient Plasma as a Potential Biomarker.

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD), common overlapping multisystemic conditions featuring symptomatic joint hypermobility, is challenging due to lack of established causes and diagnostic tools. Currently, the 2017 diagnostic criteria for hEDS are used, with non-qualifying cases classified as HSD, although the distinction remains debated. We previously showed extracellular matrix (ECM) disorganization in both hEDS and HSD dermal fibroblasts involving fibronectin (FN), type I collagen (COLLI), and tenascin (TN), with matrix metalloproteinase-generated fragments in conditioned media. Here, we investigated these fragments in patient plasma using Western blotting across diverse cohorts, including patients with hEDS, HSD, classical EDS (cEDS), vascular EDS (vEDS), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and healthy donors, uncovering distinctive patterns. Notably, hEDS/HSD displayed a shared FN and COLLI fragment signature, supporting their classification as a single disorder and prompting reconsideration of the hEDS criteria. Our results hold the promise for the first blood test for diagnosing hEDS/HSD, present insights into the pathomechanisms, and open the door for therapeutic trials focused on restoring ECM homeostasis using an objective marker. Additionally, our findings offer potential biomarkers also for OA, RA, and PsA, advancing diagnostic and therapeutic strategies in these prevalent joint diseases.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

INTRODUCTION: Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). METHODS: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. RESULTS: Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). CONCLUSIONS: In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. TRIAL REGISTRATION: DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Barriers and facilitators to application of treat-to-target management in psoriatic arthritis and axial spondyloarthritis in practice: A systematic literature review.

OBJECTIVE: To review the evidence on barriers and facilitators to application of treat-to-target (T2T) in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) in daily practice. METHODS: A systematic search was conducted in MEDLINE/Embase up to December 2023, focusing on axSpA/PsA. Any type of quantitative/qualitative original research was eligible for inclusion if barriers or facilitators to application of T2T were explored. In a qualitative synthesis, barriers/facilitators were classified by the level to which they apply (healthcare provider [HCP], patient, organisation). RESULTS: Of 28 included studies, most focused on PsA (n = 21/28). Studies included patients (n = 23/28), HCP (n = 4/28) or both (n = 1/28). In total, over 25 barriers and 15 facilitators to application of T2T were identified. At the HCP level, most studies focused on the measurement of the target, especially in PsA, highlighting that agreement among instruments was suboptimal. At the patient level, the role of patient-reported outcomes (PROs), while deemed relevant, was shown to act as a barrier to achieve targets that included PRO components. At the organisational level, the increased time and resources needed for T2T were considered a barrier, although it was noted that T2T could also reduce healthcare use and sick leave. Notably, for several components, no facilitators were identified at all. CONCLUSION: Various barriers and facilitators were identified, acting on several levels. Data in axSpA were scarce, as was evidence on certain components of T2T. Future research should address these knowledge gaps and explore how these barriers and facilitators could be targeted to improve application of T2T in practice.

A 14-year registry review (2007-2020) on nail involvement among patients with psoriasis in Malaysia.

Nail psoriasis affects 20 to 30% of psoriasis patients and is an early predictor of psoriatic arthropathy (PsA). We have evaluated the prevalence, clinical characteristics, and impact on quality of life of patients with nail psoriasis. We conducted a multicenter retrospective cohort study was of patients registered with The Malaysian Psoriasis Registry (MPR) from 1 January 1, 2007 through 31 December 31, 2020. Of the 24147 patients, 13081 (54.2%) had nail psoriasis. Patients with nail psoriasis had la ater onset of psoriasis (34.0±16.6 vs 32.9±17.6 years, p<0.001) and longer disease duration (11.4±10.5 vs 8.5±9.4 years, p<0.01), with a male to female ratio of 1.2:1. They were more likely to have a family history of psoriasis, cardiometabolic diseases, smoking history, higher body mass index, severe disease, PsA, face and scalp involvement and higher mean Dermatology Life Quality Index scores (9.36±6.84 vs 8.87±6.60). Systemic treatment and biologics were more commonly prescribed in this cohort (25.0% vs 13.2%, p<0.001). Overall, 54.2% of the MPR patients had nail involvement. Nail psoriasis was associated with longer duration of psoriasis, older age of onset, male gender, and a family history of psoriasis. It proved to be an important predictor for PsA, severe psoriasis, face and scalp involvement, increased cardiometabolic risk, and a greater impairment of quality of life.

Neutrophil exhaustion and impaired functionality in psoriatic arthritis patients.

Background: Neutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant subtype of white blood cells and are among the main actors in the inflammatory response. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting both the axial and peripheral joints. Typically associated with psoriasis, PsA can also affect multiple systems and organs, including the nails and entheses. Despite the involvement of PMNs in PsA, their specific role in the disease remains poorly understood. This study aimed to characterize the biological functions of PMNs and neutrophil-related mediators in PsA patients. Materials and methods: 31 PsA patients and 22 healthy controls (HCs) were prospectively recruited. PMNs were isolated from peripheral blood and subjected to in vitro stimulation with lipopolysaccharide (LPS), N-Formylmethionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate (PMA), or control medium. Highly purified peripheral blood PMNs (>99%) were evaluated for activation status, reactive oxygen species (ROS) production, phagocytic activity, granular enzyme and neutrophil extracellular traps (NETs) release. Serum levels of matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), TNF, interleukin 23 (IL-23), and interleukin 17 (IL-17) were measured by ELISA. Serum Citrullinated histone H3 (CitH3) was measured as a NET biomarker. Results: Activated PMNs from PsA patients displayed reduced activation, decreased ROS production, and impaired phagocytic activity upon stimulation with TNF, compared to HCs. PMNs from PsA patients also displayed reduced granular enzyme (MPO) and NET release. Serum analyses revealed elevated levels of MMP-9, MPO, TNF, IL-23, IL-17, and CitH3 in PsA patients compared to HCs. Serum CitH3 levels positively correlated with MPO and TNF concentrations, and IL-17 concentrations were positively correlated with IL-23 levels in PsA patients. These findings indicate that PMNs from PsA patients show reduced in vitro activation and function, and an increased presence of neutrophil-derived mediators (MMP-9, MPO, TNF, IL-23, IL-17, and CitH3) in their serum. Conclusions: Taken together, our findings suggest that PMNs from PsA patients exhibit an "exhausted" phenotype, highlighting their plasticity and multifaceted roles in PsA pathophysiology.

Monotherapy or combination therapy in PsA: current aspects.

Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease with heterogeneity regarding its clinical features, mainly affecting the skin and the musculoskeletal system; additionally, extra-musculoskeletal manifestations and comorbidities are common, adding complexity to its treatment. In the last decades, a plethora of therapeutic options have been available, including conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), and many recommendations have been published regarding the proper use of them in patients with PsA. In rheumatoid arthritis, the combination of conventional with bDMARDs or tsDMARDs is a common and recommended practice, whereas in PsA there is scarce data about the benefit of this combination. This review summarizes all the available data from randomized clinical trials, observational studies, and registries about the value of this therapeutic strategy.

Use of b/tsDMARDs in PsA: with or without csDMARDs Over the last years, many different b/ts DMARDs have been porven to be efficacious in psoriatic arthritis (PsA). Although in rheumatoid arthritis, it is established that most of these drugs work better in combination with conventional synthetic DMARDs (e.g methotrexate), this seems to be slightly different in PsA. Herein, we review the current literature about the combination therapy versus monotherapy of b/ts DMARDs in PsA. We present the results of this narrative review in a structured (per drug category) way, so that it is easier for the reader to find relevant information. There is no doubt that the currently available treatment options in PsA have changed the course of the disease and improved the functional status of the patients. However, as there is still a substantial proportion of patients who do not achieve remission or low disease activity, the need to find effective therapeutic regimens or follow different strategies is growing. In this direction, the combination of a conventional synthetic with biological or targeted synthetic DMARD does not seem to be more effective than the monotherapy of the latter. This seems to be more pronounced in the newer drug categories (anti-IL-17, anti-IL23 and JAKi) compared to the TNFi, where the co-administration of a csDMARD improves their survival.

Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

INTRODUCTION: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. METHODS: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. RESULTS: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. CONCLUSIONS: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.