Progression Of Psoriatic Arthritis Research Articles

EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

Multimodal Imaging of Structural Damage and Inflammation in Psoriatic Arthritis: A comparison of DMARD-Naive and DMARD-Failure Patients.

To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings. Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression. At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600). At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies. EudraCT: 2017-003900-28.

Exploring the Role of Microbiome Alterations in the Pathogenesis of Psoriatic Arthritis: A Multidisciplinary Approach

Psoriatic arthritis (PsA) is a complex, chronic inflammatory disease with intertwined dermatological and rheumatological manifestations, profoundly affecting patients’ quality of life. Recent advances have highlighted the potential role of microbiome alterations, both in the gut and skin, in the pathogenesis of PsA. This review synthesizes current research on the microbiome’s involvement in PsA, emphasizing the interplay between microbial dysbiosis and immune system modulation. Emerging evidence suggests that shifts in the composition and function of the gut and skin microbiota can trigger or exacerbate PsA by promoting systemic inflammation and autoimmune responses. Studies have identified specific microbial taxa associated with PsA, revealing potential biomarkers for early diagnosis and therapeutic targets. However, the precise mechanisms through which microbiome alterations influence PsA pathophysiology remain incompletely understood. Future research should focus on longitudinal studies to further understand the causal relationships between microbiome changes and PsA onset and progression. Integrating varying approaches, including metagenomics, transcriptomics, and metabolomics, will provide a comprehensive understanding of microbial functions and host-microbiome interactions. Additionally, investigating the effects of microbiome-modulating interventions, such as probiotics, prebiotics, and dietary modifications, could guide innovative therapeutic strategies. This multidisciplinary approach, combining dermatological and rheumatological insights, holds promise for unraveling the complexities of PsA and improving patient outcomes through personalized medicine. By advancing our knowledge of

Coronavirus disease 2019 and psoriatic arthritis: Features and connections

AbstractBackgroundLittle is known about the characteristics of patients with psoriatic arthritis (PsA) during the coronavirus disease 2019 (COVID‐19) pandemic. This study aimed to evaluate the impact of COVID‐19 on PsA progression and comprehend the role of COVID‐19 vaccination in the infection course.MethodsA total of 163 adult patients with PsA from 15 provinces in China were enrolled in this multiregional observational study from January 14, 2023, to March 22, 2023. Data on patient demographics, COVID‐19 status, and disease characteristics were collected through a structured questionnaire survey.ResultsSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections could worsen PsA, with 29.0% of patients experiencing deteriorating symptoms. Psoriasis was the symptom most exacerbated (61.1%), followed by peripheral arthritis (52.8%) and dactylitis (25.0%). Compared with the patients whose arthritic condition was stable before contracting COVID‐19, those with active PsA experienced more severe COVID‐19 symptoms, reporting higher self‐assessed symptom severity scores and a greater prevalence of dyspnea (42.9% vs. 7.3%). Moreover, although full vaccination (≥2 doses) could not prevent COVID‐19, it could alleviate the infection symptoms, including diarrhea, fatigue, appetite changes, and spondyloarthritis. Additionally, fully vaccinated individuals had a higher probability of avoiding deterioration of their PsA condition after infection.ConclusionActive PsA and lack of COVID‐19 vaccination are risk factors for worsening COVID‐19 symptoms and PsA condition after infection. The evidence from this real‐world study suggests that COVID‐19 may exacerbate PsA.

From Psoriasis to Psoriatic Arthritis: Ultrasound Insights Connecting Psoriasis with Subclinical Musculoskeletal Inflammation and the Path to Psoriatic Arthritis.

This review summarizes the literature about the transition from psoriasis to psoriatic arthritis (PsA), focusing on musculoskeletal ultrasound (MSUS) for detecting subclinical inflammation and its role in diagnosis and triage of high-risk patients. MSUS effectively detects subclinical musculoskeletal inflammation in patients with psoriasis; however, some of these lesions are non-specific and can be found in healthy individuals. Preliminary evidence suggest that subclinical sonographic findings may predict progression to PsA in psoriasis patients. MSUS can also improve referrals' accuracy and its integration in the PsA classification criteria may improve early PsA detection. MSUS is a valuable tool for detecting subclinical abnormalities in psoriasis patients, which indicate an increased likelihood of progressing to PsA. Its integration into referral protocols and clinical use could improve PsA diagnosis. We propose an MSUS-inclusive algorithm for PsA referrals and triage, which requires validation. The potential of early intervention in reducing PsA progression in psoriasis patients with subclinical inflammation remains to be established.

Effects of Secukinumab on Enthesiophyte and Erosion Progression in Psoriatic Arthritis-A One-year Double-blind, Randomized, Placebo-controlled Trial Utilizing High-resolution Peripheral Quantitative Computed Tomography

Background This study aimed to ascertain the effect of secukinumab on erosion and enthesiophyte progression in psoriatic arthritis (PsA) by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This was a one-year double-blind, randomized, placebo-controlled trial (NCT0362386740). Patients with erosion in the metacarpophalangeal joints (MCPJ) 2-4 were randomised in a 1:1 ratio to either the secukinumab or placebo group. HR-pQCT of the MCPJ 2-4 were performed at baseline, week-24 and 1-year. Progression of enthesiophyte were defined as changes in enthesiophyte volume exceeding smallest detectable change (SDC) (0.12mm3) or the identification of any new enthesiophyte. Partial repair of erosion was defined as a reduction in erosion volume greater than SDC (0.1mm3). Results Forty patients (age: 51.9± 13.4 years, 20 [50%] male) were recruited. Thirty-four patients who completed study treatment were included in the per-protocol analysis. The erosion volume at baseline, week-24 and week-48 revealed significant reduction in the secukinumab group while no differences in the placebo group (Figure-3A). There was a trend suggesting that fewer patients developed new-erosions in the secukinumab group (one-erosion in one-patient) compared to the placebo group (six-erosions in five-patients) (p=0.078) (Figure-3B). A significantly higher proportion of erosions with partial healing was observed in the secukinumab group compared with the placebo group [51%vs30%, p=0.029] (Figure-3C). Regarding enthesiophyte, a total of 25-enthesiophytes were identified in both the secukinumab and placebo groups at baseline. The enthesiophyte volume at baseline, week-24 and week-48 revealed significant differences in the secukinumab group while no differences in the placebo group (Figure-3D). While one (one-enthesiophyte in one-patient) and four-enthesiophytes (four-enthesiophytes in three-patients) were newly identified in the secukinumab group and placebo group respectively (Figure-3E), the proportion of enthesiophyte progression was numerically higher in the placebo group than the secukinumab group [40%vs16%, p=0.114] at week 48 (Figure-3F). GEE results showed that the odds ratio (OR) for enthesiophyte progression in the secukinumab group was 0.264 (95% CI: 0.080-0.878, p=0.030), while the OR for partial erosion healing in the secukinumab group was 2.816 (95% CI: 1.109 to 7.153, p=0.029), adjusting for tender-joint-counts. Conclusions Secukinumab demonstrates a potential benefit in facilitating partial erosion repair and preventing enthesiophyte progression in PsA.

The optimal use of tildrakizumab in the elderly via improvement of Treg function and its preventive effect of psoriatic arthritis.

As a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA). To achieve this, a multi-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment. The severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7 months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p<0.0001; LR 6. 16, p=0.01). Tildrakizumab improved the number and function of Tregs, which had been reduced by aging. Tildrakizumab demonstrated significant efficacy in improving various pathological factors associated with PsA. These factors include the reduction of NFB, enlargement of capillaries, and inhibition of PsA progression. The hazard ratio for progression to PsA was found to be 0.06 (95% confidence interval: 0.0007-0.46, p=0.007), indicating a substantial reduction in the risk of developing PsA. Tildrakizumab's effectiveness in improving skin lesions can be attributed to its ability to enhance the number and function of Tregs, which are known to decline with age. Furthermore, the drug's positive impact on NFB activity and capillary enlargement, both of which are recognized as risk factors for PsA, further contribute to its inhibitory effect on PsA progression.

Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment.

Psoriatic arthritis (PsA) is a persistent, inflammatory disease that affects individuals with psoriasis, arthritis, and enthesitis. Research has demonstrated that inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), and interleukin-17 (IL-17) play a pivotal role in both the onset and progression of PsA. These cytokines are generated by activated immune cells and stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone. The blocking of these cytokines has become a successful treatment strategy for PsA, as biological drugs that inhibit TNF-α, IL-23, and IL-17 have demonstrated notable clinical benefits. The association between PsA and other types of inflammatory cytokines or chemokines, excluding TNF-α, IL-23, and IL-17, has been extensively investigated in numerous studies. These findings may provide a chance for the discovery of novel therapeutic agents targeting other molecules, distinct from the currently approved biologics and targeted synthetic disease-modifying anti-rheumatic drugs. In this review, we discuss the current understanding of the role of inflammatory cytokines in PsA pathogenesis and clinical implications of targeting these cytokines for PsA treatment.

Real-world effectiveness of golimumab in adult patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis and an inadequate response to initial TNFi therapy in Greece: the GO-BEYOND prospective, observational study.

The impact of golimumab (GLM) on remission or low disease activity (LDA) was evaluated in patients with moderate-to-severe rheumatoid arthritis (RA), progressive psoriatic arthritis (PsA), or severe axial spondyloarthritis (axSpA), who failed previous treatment for their rheumatic disease with one initial tumor necrosis factor α inhibitor (TNFi). This is a multicenter, prospective, real-world observational 18-month study, conducted in Greece. The primary endpoint, assessed at 6 months, included the proportion of patients attaining LDA and/or remission (Disease Activity Score for 28 joints based on C-reactive protein [DAS28-CRP] ≤ 3.2), minimal disease activity (MDA; MDA criteria), and moderate disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score 4-7), respectively. Other endpoints evaluated the persistence to GLM treatment and its impact on patients' work productivity (Work Productivity and Activity Impairment [WPAI] instrument) and quality of life (QoL; EuroQoL5 dimensions 3 levels [EQ-5D-3L] questionnaire). Descriptive statistics, the Wilcoxon signed-rank test, and Kaplan-Meier method were used for analyses. At 6 months, LDA was achieved by 46.4% of patients with RA, MDA by 57.1% of patients with PsA, and BASDAI 4-7 by 24.1% of patients with axSpA. For all study patients, persistence rates on GLM were high (85.1-93.7%) over 18months; all WPAI domain scores and the EQ-5D-3L index score improved significantly (p < 0.001) from baseline to 18months. GLM treatment was effective in patients with RA, PsA, or axSpA who had failed previous treatment with one TNFi and led to significant WPAI and QoL improvements. Persistence rates were high. Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6995 .

Non-Redundant Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN-101).

CD28 and inducible T cell costimulator (ICOS) appear to have nonredundant roles in T cell activation and adaptive immunity. We undertook this study to characterize in vitro and in vivo the therapeutic potential of acazicolcept (ALPN-101), an Fc fusion protein of a human variant ICOS ligand (ICOSL) domain designed to inhibit both CD28 and ICOS costimulation, in inflammatory arthritis. Acazicolcept was compared in vitro with inhibitors of either the CD28 or ICOS pathways (abatacept and belatacept [CTLA-4Ig], prezalumab [anti-ICOSL monoclonal antibody]) in receptor binding and signaling assays, and in a collagen-induced arthritis (CIA) model. Acazicolcept was also compared in cytokine and gene expression assays of peripheral blood mononuclear cells (PBMCs) from healthy donors or rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients stimulated with artificial antigen-presenting cells (APCs) expressing CD28 and ICOS ligands*. Acazicolcept bound CD28 and ICOS, prevented ligand binding, and inhibited human T cell functional interactions, matching or exceeding the activity of CD28 or ICOS costimulatory single-pathway inhibitors tested individually or in combination. Acazicolcept administration significantly reduced disease in the CIA model and more potently than abatacept. Acazicolcept also inhibited proinflammatory cytokine production from stimulated PBMCs in cocultures with artificial APCs and demonstrated unique effects on gene expression distinct from those induced by abatacept, prezalumab, or a combination of both. Both CD28 and ICOS signaling play critical roles in inflammatory arthritis. Therapeutic agents such as acazicolcept that coinhibit both ICOS and CD28 signaling may mitigate inflammation and/or disease progression in RA and PsA more effectively than inhibitors of either pathway alone.

Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients’ clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan–Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.

Biologic Disease-Modifying Antirheumatic Drugs for Preventing Radiographic Progression in Psoriatic Arthritis: A Systematic Review and Network Meta-Analysis.

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66–8.29), etanercept (OR 4.19, 95% CI 1.65–10.61), certolizumab pegol (OR 2.83, 95% CI 1.55–5.2), secukinumab 300 mg (OR 2.63, CI 1.62–4.27), infliximab (OR 2.54, CI 1.13–5.69), ixekizumab (OR 2.22, 95% CI 1.06–4.65), golimumab (OR 2.21, 95% CI 1.24–3.93), and abatacept (OR 1.54, 95% CI 1.03–2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) −0.59, 95% CI −0.87, −0.3), etanercept (SMD −0.51, 95% CI −0.78, −0.23), adalimumab (SMD −0.45, 95% CI −0.64, −0.26), ixekizumab (SMD −0.37, 95% CI −0.62, −0.12), secukinumab 300 mg (SMD −0.33, 95% CI −0.50, −0.15), golimumab (SMD −0.33, 95% CI −0.58, −0.09), secukinumab 150 mg (SMD −0.25, 95% CI −0.43, −0.07), certolizumab pegol (SMD −0.23, 95% CI −0.44, −0.03), and ustekinumab (SMD −0.19, 95% CI −0.35, −0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.

The burden of progression of psoriatic arthritis. All-Russian register data

Psoriatic arthritis (PsA) is a complex immune-mediated disease in which a third of patients with psoriasis (PsO) have a inflammatory lesion of both the musculoskeletal system (peripheral joints and axial structures) and extra-articular manifestations (dactylitis, enthesitis, nail PsO, uveitis and inflammatory bowel disease). To assess the burden of PsA progression in real practice according to the Russian register of PsA patients. Seven hundred thirty seven M/F=350 (47.5%)/387 (52.5%) patients with PsA from the Russian register of PsA patients were included. Mean age 47.412.7 yrs., duration of PsO 200.6158.9 mo., PsA 79.681.9 mo. All patients were divided into 2 groups by PsA duration: 1st gr 36 mo 288 (39.1%) and 2nd gr 36 mo 449 (60.9%). All patients underwent standard clinical examination of PsA activity. Tender (68) and swelling (66) joint count (TJC, SJC), DAPSA, LEI, tenderness of the plantar fascia, PsO BSA (%), PASI, HAQ-DI, PsAID-12, BMI (kg/m2), ESR (mm/h), CRP (mg/l) and comorbidities by ICD-10 were evaluated. Parametric and non-parametric methods of statistical analysis were used. All p0.05 were considered to indicate statistical significance. In patients with PsA duration 36 mo we found significant prevalence of erosions by X-Ray, axial PsA, BMI30 kg/m2, HAQ-DI1, PsAID-124, arterial hypertension, metabolic syndrome and overall comorbidity (p0.05). There were no significant differences between groups in PsO severity by BSA3%, PASI1, LEI1, TJC, SJC, dactylitis, ESR30 mm/h, CRP10 mg/l, DAPSA, diabetes mellitus, hyperlipidemia, coronary heart disease and liver damage (p0.05). Сonclusion. Long-standing stage PsA is associated with erosions, axial PsA, worst health related quality of life, functional disability and increased cardio-metabolic disorders and overall comorbidity. Our results support the idea to start bDMARDs at early stage of PsA, it can improve better outcomes.

Brodalumab Is Associated with High Rates of Complete Clearance and Quality of Life Improvement: A Subgroup Analysis of Patients with Psoriasis and Concomitant Psoriatic Arthritis

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis that significantly impairs physical function and quality of life (QoL). Prompt therapeutic intervention is crucial for limiting PsA progression and preventing disability. Objectives: The aim of this study was to compare the efficacy of brodalumab versus ustekin­umab and the impact on QoL in patients with moderate-to-severe plaque psoriasis, by concomitant PsA status. Methods: This post hoc analysis of pooled data from the phase 3 AMAGINE-2 and -3 trials evaluated complete skin clearance (100% improvement of Psoriasis Area and Severity Index [PASI 100]), improvement in symptom severity (Psoriasis Symptom Inventory [PSI] response), and QoL (Dermatology Life Quality Index [DLQI] score of 0/1) by concomitant PsA status. A competing risk model assessed cumulative incidence over 52 weeks with outcomes of PASI 100 or inadequate response. Results: This analysis included 929 patients with moderate-to-severe psoriasis. Concomitant PsA was present in 79/339 (23%) and 110/590 (19%) patients receiving brodalumab 210 mg and ustekinumab, respectively. At Week 52, odds ratios (ORs) (95% confidence intervals [CIs]) for complete clearance with brodalumab versus ustekin­umab were 3.15 (1.52–6.55, p = 0.0015) in patients with concomitant PsA and 3.05 (2.19–4.26, p < 0.0001) in patients without concomitant PsA. Corresponding Week 52 ORs (95% CIs) for DLQI 0/1 with brodalumab versus ustekinumab were 2.05 (1.07–3.90, p = 0.0277) and 1.83 (1.32–2.53, p = 0.0002); Week 52 ORs (95% CIs) for PSI ≤8 with brodalumab versus ustekinumab were 3.42 (1.43–8.18, p = 0.0036) and 1.40 (1.01–1.95, p = 0.0434). The 52-week cumulative incidence of patients achieving PASI 100 was significantly higher for brodalumab versus ustekinumab in patients with concomitant PsA (p = 0.0001) and in those without concomitant PsA (p < 0.0001). Conclusions: Treatment with brodalumab rapidly results in high levels of complete and sustained skin clearance and greater cumulative treatment benefit in patients with moderate-to-severe psoriasis versus ustekinumab, regardless of concomitant PsA status.

Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints.

Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.

25760 Are there different patient journeys from psoriasis to psoriatic arthritis?

Understanding the progression from psoriasis (PsO) to psoriatic arthritis (PsA) is crucial to prevention strategies. Besides several risk factors, little is known about the complex patterns of progression due to heterogeneous medical and treatment history in the patient population. To identify and characterize different patient journeys from PsO to PsA, we leveraged longitudinal electronic health records (EHRs) of a wide range of medical events and their temporal sequences with machine learning (ML) techniques. We used Optum deidentified EHR database (2007-2019) to identify subjects with PsO (≥1 inpatient or ≥2 outpatient diagnosis). Using the first PsO diagnosis date as the index date, subjects were required to have records of ≥2 years preindex and ≥3 years postindex. Subjects with preindex PsA diagnosis were excluded. To examine the disease progression holistically, all diagnosis and medication records pre- and postindex up to the first diagnosis of PsA were used as the input data. Application of the ML pipeline resulted in segmentation of the cohort (a total of ∼130k PsO patients; 10% later developing PsA) into 7 clusters. The PsO clusters showed varying rates (3-13%) and median times (16-34 months) of progression to PsA. In conclusion, we identified distinct patterns of PsO to PsA progression by applying ML to EHR data, revealing unique combinations of patient demographics, potential risk factors, treatment, and health care utilization in each cluster.

Enthesis lesions are associated with X-ray progression in psoriatic arthritis.

To analyze the relationship among enthesis ultrasound (US) lesions and radiological structural damage in psoriatic arthritis (PsA) patients. Consecutive PsA patients with swelling of at least 1 of the 2nd to 5th metacarpophalangeal joints were included. Clinical and demographic data were collected. The Madrid Sonographic Enthesitis Index (MASEI) was selected to evaluate the enthesis, with its total score and MASEI-activity and MASEI-structural damage subscores. The modified Sharp van der Heijde method for PsA and the New York criteria for sacroiliitis were selected to evaluate cumulative bone damage on X-rays. Twenty-seven patients were included. Male gender, older age, longer PsA duration and acute reactant factors were associated with greater bone cumulative damage. Enthesis tendon thickening, enthesophytes, total MASEI and the MASEI-structural damage subscore showed significant correlations with radiographic peripheral and sacroiliac damage scores. Tendon thickening and enthesophytes were the enthesis lesions more frequently associated with radiographic damage in PsA. The enthesis MASEI score was associated with axial and articular radiographic structural damage in PsA patients. The MASEI-structural damage subscore correlated better with cumulative bone damage in PsA than the MASEI-activity subscore.

Synovial Immunohistological Biomarkers of the Classification of Undifferentiated Arthritis Evolving to Rheumatoid or Psoriatic Arthritis.

Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA.Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns.Results: One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3+ T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found.Conclusions: Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.

Corticosteroid injection treatment for dactylitis in psoriatic arthritis.

Dactylitis – a hallmark clinical feature of psoriatic arthritis (PsA) – that occurs in 30–50% of PsA patients, is a marker of disease severity for PsA progression, an independent predictor of cardiovascular morbidity and impairs the motor functions of PsA patients. There is a paucity of evidence for the treatment due to the absence of randomized controlled trials assessing dactylitis as a primary endpoint and current practice arises from the analysis of dactylitis as a secondary outcome. Corticosteroid (CS) injections for dactylitis in PsA patients are a therapeutic treatment option for patients with isolated dactylitis or for patients with flares in tendon sheaths, despite stable and effective systemic treatment. The aim of this narrative review is to briefly illustrate the clinical aspects of dactylitis in PsA, the imaging and clinimetric tools used to diagnose and monitor dactylitis, the current treatment strategies and principally to provide a comprehensive picture of the clinical efficacy and safety with ultrasound-guide and blind techniques of CS injections for dactylitis in PsA patients.

Secukinumab's effect on structural damage progression in psoriatic arthritis: longitudinal mixture modelling of FUTURE-1 and FUTURE-5.

Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of treatment effects in subgroups of patients with different rates of structural damage progression. We analysed data from two large Phase-3 trials of secukinumab in PsA patients, FUTURE-1 (NCT01392326, n=606) and FUTURE-5 (NCT02404350, n=996), where different posologies ranging from 75 mg to 300 mg were used. We applied a longitudinal Bayesian mixture model with random effects to account for the variability in the repeated radiographic assessments. "Fast progressors" were defined post hoc as patients with a 50% model-estimated probability to progress at least 0.5 mTSS/year faster than an average patient. Higher baseline inflammation and higher body weight were identified as significant predictors of radiographic progression (multivariate model). Model-estimated structural damage progression in an average patient treated with secukinumab 150 mg subcutaneous (s.c.) was slower (0.04 mTSS/year; 95% CI -0.28, 0.34) compared to a patient treated with placebo (0.94 mTSS/year; 95% CI 0.45, 1.45). According to the model, the subgroup of "fast progressors" (hsCRP ≥26 mg/L, body weigth ≥94 kg, inadequate response to prior anti-TNF-alpha, structural damage ≥42 mTSS) treated with secukinumab 150 mg s.c. progressed at 0.56 mTSS/year (95% CI 0.02, 1.09) and 1.46 mTSS/year (95% CI 0.81, 2.11) when treated with placebo. Greater systemic inflammation and higher body weight at baseline were identified as significant predictors of progression. Even patients with fast radiographic progression could experience a beneficial effect with secukinumab that holds promise to prevent further mobility loss.