Subclinical Enthesopathy in Psoriasis-An Ultrasonographic Study.

The present study is aimed at assessing the presence and prevalence of subclinical entheseal changes in Psoriasis (PsO) patients using musculoskeletal ultrasonography (US), conjoined with the analysis of possible differences in terms of demographic, clinical, or biological features. We carried out an observational study on 54 patients with PsO and 40 controls. Subclinical enthesopathy, according to OMERACT definitions, was identified in 20 of the psoriasis patients (37.03%), a significantly difference compared to the controls (5 patients; 10.20%). A comparison between US examinations for psoriasis patients and controls indicates that all the examined areas manifested changes in a significantly higher percentage of patients than the controls. The most common structural changes were represented by thickened tendon (85%), calcification (65%), erosions (35%), power Doppler (PD) signal (20%), and bursitis (5%). The difference in mean MASEI (Madrid Sonographic Enthesitis Index) score between the psoriasis and control groups was statistically significant (10.56 + 2.96 vs. 2.9 + 2.20; p < 0.0001). In conclusion, ultrasound is an easily accessible and vital follow-up method for psoriasis patients to enable an early, subclinical detection of entheseal involvement, i.e., the first red-flag sign for a future transition to psoriatic arthritis (PsA).

Enthesopathies - Mechanical, inflammatory or both?

Entheses have the challenging task of transferring biomechanical forces between tendon and bone, two tissues that differ greatly in composition and mechanical properties. Consequently, entheses are adapted to withstand these forces through continuous repair mechanisms. Locally specialized cells (mechanosensitive tenocytes) are crucial in the repair, physiologically triggering biochemical processes to maintain hemostasis. When repetitive forces cause "material fatigue," or trauma exceeds the entheses' repair capacity, structural changes occur, and patients become symptomatic. Clinical assessment of enthesopathies mainly depends on subjective reports by the patient and lacks specificity, especially in patients with central sensitization syndromes. Ultrasonography has been increasingly used to improve the diagnosis of enthesopathies. In this article, the literature on how biomechanical forces lead to entheseal inflammation, including factors contributing to differentiation into a "clinical enthesitis" state and the value of ultrasound to diagnose enthesopathies will be reviewed, as well as providing clues to overcome the pitfalls of imaging.

The role of GDF5 in regulating enthesopathy development in the Hyp mouse model of XLH.

X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of growth/differentiation factor 5 (Gdf5) is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.

X-linked hypophosphatemia (XLH) is a rare bone disorder that leads to short stature and poorly mineralized bones. As adults, patients with XLH often develop a mineralization of the bone-tendon attachment site, called enthesopathy, which results in significant pain. We previously showed that Achilles bone-tendon attachment sites (entheses) in mice with XLH (Hyp) have an enthesopathy characterized by increased bone morphogenetic protein (BMP) signaling. In the current studies, we show that treating Hyp mice with the BMP signaling inhibitor palovarotene prevents enthesopathy, demonstrating that the increased BMP signaling in Hyp entheses leads to enthesopathy development. We also reported that gene expression of Gdf5, which activates BMP signaling, is enhanced in Hyp entheses. Therefore, to determine if the enhanced Gdf5 expression leads to the increased BMP signaling seen Hyp entheses, Gdf5 was deleted from Hyp mice and also deleted specifically in the entheses of Hyp mice. In both mouse models, enthesopathy development was attenuated, demonstrating that the increased Gdf5 expression in Hyp entheses plays a role in enthesopathy development. These data indicate that blocking GDF5 and BMP signaling may prevent enthesopathy in patients with XLH.

Extraarticular manifestations of juvenile idiopathic arthritis and their impact on health-related quality of life.

OBJECTIVES: The objective of this study is to investigate extraarticular manifestations (EAMs) in patients with juvenile idiopathic arthritis (JIA) and assess their impact on health-related quality of life (HRQoL) among these patients. METHODS: This cross-sectional analytic study was carried out on 117 patients with JIA. EAMs were identified clinically by history and examination. Sicca symptoms, peripheral neuropathy, enthesitis, and skin lesions were picked up during clinical examination. Pulmonary involvement was evaluated by high-resolution CT chest. Patients were assessed by abdominal ultrasonography to assess the size of liver and spleen. Atlantoaxial subluxation was evaluated by cervical spine x-rays. Patients were evaluated by Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL-3 arthritis module. RESULTS: The median age of patients was 14 years with a median disease duration 4 years, 82.9% were females. Of the studied 117 JIA patients, 85 patients (72.6%) had at least one EAM. Persistent fatigue (51.3%) was the most prevalent EAM, followed by recurrent skin rash (16.2%), enthesitis (15.4%), recurrent fever (13.7%), and uveitis (12%). Patients with EAMs scored significantly lower in physical functioning (p = 0.001), emotional functioning (p < 0.001), social functioning (p = 0.005), and school functioning (p = 0.001). Regarding PedsQL arthritis module, patients with EAM had also significantly lower scores than did patients without EAM on the domains of pain and hurt (p < 0.001), daily activities (p = 0.008), and worry (p = 0.001). RESULTS: EAMs are prevalent among JIA patients and have a negative impact on their HRQoL. So, early identification and treatment are highly recommended. Key Points • A large percentage of JIA patients experienced at least one extraarticular manifestation (EAM). • Persistent fatigue and recurrent skin rash are the most prevalent EAMs in JIA patients. • JIA patients with EAMs have worse scores in almost all domains of HRQoL.

Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic.

BACKGROUND: Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA). METHODS: Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups. RESULTS: Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA. CONCLUSION: The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

Unveiling Metabolic Similarities of Entheses in Patients with Psoriasis and Psoriatic Arthritis Using Noninvasive In Vivo Molecular Imaging: Results From a Cross-sectional Exploratory Study.

OBJECTIVE: We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis. METHODS: A cross-sectional study (MSOT and Arthrosonography in PsA) in biologic disease-modifying antirheumatic drug-naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT-measured hemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT-measured analytes were compared between entheses with and without clinical and ultrasound anomalies. RESULTS: Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (P = 0.014) and lipid signals (P = 0.020), respectively. CONCLUSION: Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Hematological indices in psoriatic enthesopathy: relation to clinical and ultrasound evaluation.

BACKGROUND: Enthesopathy is considered a crucial aspect of assessment and outcome in psoriatic arthritis (PsA). Musculoskeletal ultrasound (MSUS) is a critical tool for accurately detecting enthesitis. Recent research focuses on identifying simple biomarkers for detecting and monitoring psoriatic enthesopathy. Red cell distribution width (RDW), mean platelet volume (MPV), and neutrophil/lymphocyte ratio (NLR) are components of a complete blood count (CBC) and are reliable bio-inflammatory markers in various rheumatic diseases. AIM OF WORK: To measure MPV, RDW, and NLR in psoriatic enthesopathy and determine their relationship to disease activity and MSUS findings. PATIENTS AND METHODS: This study focused on 30 people with psoriatic arthritis (PsA) as per CASPAR criteria, along with 20 control subjects. Enthesopathy was evaluated clinically using the Leeds Enthesitis Index (LEI). The modified Disease Activity Index of Psoriatic Arthritis (DAPSA28) was calculated, and RDW, MPV, NLR, CRP, and ESR were measured. Each enthesis in LEI was radiologically assessed using plain radiography and MSUS according to OMERACT definitions. RESULTS: There was a significant relationship between clinical tenderness, the presence of enthesophytes on plain radiography, and MSUS findings at entheses sites (p < 0.001 for each). Psoriatic patients had higher levels of RDW and MPV (p < 0.001 and 0.01, respectively) than controls, with no significant differences in NLR (p = 0.189) between the two groups. RDW and MPV levels were positively correlated with the DAPSA28 score. CONCLUSION: Monitoring PsA disease activity can be improved by considering RDW and MPV as reliable indicators and using them to screen for psoriatic enthesopathy with MSUS indices. Key points • Clinically identifying enthesitis in patients with PsA can be challenging. Imaging MSUS indices hold promise for objective analysis, but there is no consensus on which indices to use in clinical trials and daily practice. • Patients with psoriatic enthesopathy have higher RDW and MPV levels, which are positively correlated with DAPSA28 score. • RDW and MPV can be considered in the turn of improved screening of psoriatic enthesopathy with MSUS scores.

Assessment of enthesopathy in conventional pelvis radiography: Another tool for spondyloarthritis diagnosis beyond sacroiliitis.

INTRODUCTION/OBJECTIVES: Enthesitis is a cardinal feature of spondylarthritis (SpA), and the pelvis is a common site of enthesitis. This study aimed to establish the association between pelvic enthesis involvement on pelvic X-ray and SpA diagnosis through a radiographic enthesis index (REI) and to assess the reliability and accuracy of this REI. MATERIALS AND METHODS: The participants were SpA patients and a control group composed of patients with chronic lumbar pain without SpA. Three blinded observers assessed each pelvic radiography three times. Three zones were used: Zone I (ZI), the iliopubic ramus; Zone II (ZII), the pubic symphysis, and Zone III (ZIII), the ischiopubic ramus. A grading system was created from 0 to 3 [Grade 0, normal; Grade 1, minimal changes (subcortical bone demineralization and/or periosteal wishkering, seen as radiolucency and trabeculation of the cortical bone upon tendon insertion); Grade 2, destructive changes (Grade 1 findings and erosions at the enthesis site); and Grade 3, findings of Grade 2 plus >2 mm whiskering out of the cortical bone) for the REI. The sum of the results of the three zones was called the total REI. For statistical analysis, we used the weighted kappa statistic adjusted for prevalence and bias using Gwet's agreement coefficient. RESULTS: We enrolled 161 patients, 111 of them with SpA (39.6 % with axial SpA and 47.7 % with peripheral SpA) and 50 without SpA. In the SpA group, 36.7 % and 25.7 % had REI Grades 2 and 3 in ZIII, respectively, while only 6 % of the controls had these grades. For ZI, the frequency of Grades 1 to 3 was 42.3 % in the SpA group (8.1 %, 14.4 %, and 19.8 %, respectively), compared to only 2 % in the controls. ZII was unaffected in most of the patients with SpA (82.9 %) and in the controls (98 %). In the control group, Grade 0 was the most common REI grade in all three zones. The agreement was almost perfect for each zone and between the independent readers. The ROC-curve analysis showed that the highest performance areas were the total REI, ZIII, and ZI. Most (75 %) of the SpA patients without sacroiliitis on X-ray were REI-positive. The sensitivity of the REI for SpA diagnosis was 82 %, while the sensitivity of sacroiliitis on X-ray was 38.7 %. CONCLUSIONS: The assessment of pelvic enthesis using the REI on pelvic radiography may be useful for SpA diagnosis. Total REI, ZIII, and ZI had the highest accuracy and almost perfect reliability. The REI is especially helpful in patients without sacroiliitis on imaging.

Axial Spondyloarthritis: an overview of the disease.

Axial Spondyloarthritis (axSpA) is a chronic, inflammatory, immune-mediated rheumatic disease that comprises two subsets, non-radiographic and radiographic axSpA, and belongs to a heterogeneous group of spondyloarthritides (SpA). Over the years, the concept of SpA has evolved significantly, as reflected in the existing classification criteria. Considerable progress has been made in understanding the genetic and immunological basis of axSpA, in studying the processes of chronic inflammation and pathological new bone formation, which are pathognomonic for the disease. As a result, new medication therapies were developed, which bring more effective ways for disease control. This review presents a brief overview of the literature related to these aspects of disease after summarising the available information on the topic that we considered relevant. Specifically, it delves into recent research illuminating the primary pathological processes of enthesitis and associated osteitis in the context of inflammation in axSpA. The exploration extends to discussion of inflammatory pathways, with a particular focus on Th1/Th17-mediated immunity and molecular signaling pathways of syndesmophyte formation. Additionally, the review sheds light on the pivotal role of cytokine dysregulation, highlighting the significance of the IL-23/17 axis and TNF-α in this intricate network of immune responses which is decisive for therapeutic approaches in the disease.

Patients With Psoriatic Arthritis-Related Enthesitis and Persistence on Tofacitinib Under Real-World Conditions.

OBJECTIVE: Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. METHODS: This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. RESULTS: Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. CONCLUSION: In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Validation and incorporation of digital entheses into a preliminary GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis.

OBJECTIVES: The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system. METHODS: The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis. RESULTS: 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39-0.71) and intraobserver reliability good to excellent (κ 0.80-0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes). CONCLUSIONS: We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.

Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA). METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data. RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported. CONCLUSION: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

OBJECTIVES: To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study. METHODS: Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0-6) and Dactylitis Severity Score (range, 0-60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0-100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test. RESULTS: Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03). CONCLUSION: In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT03158285; Registered: May 16, 2017. Key Points • At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR). • Achieving ER was associated with achieving DR and vice versa through the end of study. • Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

Peripheral Joint and Enthesis Involvement in Patients With Newly Diagnosed Inflammatory Bowel Disease: Symptoms, and Clinical and Ultrasound Findings - A Population-Based Cohort Study.

OBJECTIVES: Musculoskeletal [MSK] manifestations in patients with inflammatory bowel disease [IBD] are common and associated with poorer outcomes. Hence, early detection is important to optimally tailor treatment. We aimed to determine the prevalence and distribution of inflammatory lesions in peripheral joints and entheses in newly diagnosed IBD patients. DESIGN: Patients with newly diagnosed IBD from a prospective population-based inception cohort were consecutively included. Data on MSK symptoms were collected by questionnaires and by structured rheumatological interview. Peripheral joints and entheses were assessed clinically and by ultrasound [US], using standardized definitions. RESULTS: Of 110 included patients (mean age: 42 years, 40% male, 70 with ulcerative colitis [UC], 40 with Crohn's disease [CD]), a history of ≥1 peripheral musculoskeletal symptom was reported by 49%. Clinical examination revealed peripheral MSK manifestations in 56 [52.3%] patients; 29 [27.1%] had ≥1 tender and/or swollen joints and 49 [45.8%] ≥1 tender entheses. Small peripheral joints were predominantly affected. US found inflammation in ≥1 joint or enthesis in 52 [49.5 %] patients; 29 [27.4 %] had US synovitis in ≥1 joint, while 36 [34%] had US enthesitis. Fibromyalgia classification criteria were fulfilled in seven [7.9%] patients. There was no difference in clinical or US findings between patients with UC and CD, nor between patients with active and inactive IBD. CONCLUSION: Half of the patients with newly diagnosed IBD had inflammation in their peripheral joints and/or entheses, documented by rheumatological clinical and US evaluations. This indicates a need for multidisciplinary collaboration to ensure an optimal therapeutic strategy for suppressing inflammation in all disease domains.

Ultrasonographic Evaluation of Nail Involvement in Patients With Axial Spondyloarthritis.

OBJECTIVES: This study aimed to evaluate the nail units of patients with axial spondyloarthritis (ax-SpA) using ultrasound and to identify any subclinical changes. We also aimed to examine the relationship between clinical enthesitis scores and nail involvement in patients with ax-SpA. METHODS: The study included 40 patients with ax-Spa, 40 patients with psoriatic arthritis (PsA), and 40 healthy controls. The thickness of the nail plates, morphological changes, the thickness of the proximal nail units, the thickness of the nail beds, and power Doppler signal intensities were evaluated and compared. Maastricht Ankylosing Spondylitis Enthesitis Score and Spondyloarthritis Research Consortium of Canada Enthesitis Index were also evaluated in patients with ax-SpA. RESULTS: There was no significant difference between the thickness of the nail plates of the three groups (P > .05). The first nail bed thickness of ax-SpA cases was significantly higher than the control group (P = .046), and the fourth and fifth nail proximal unit thicknesses of the control group were significantly lower than the ax-SpA and PsA groups (P = .023, P = .017). We also found that the Wortsman scores of the cases with PsA were significantly higher than the ax-SpA and control groups (P = .0001). CONCLUSION: The thickness of the proximal nail unit adjacent to the insertion of the digital extensor tendon, which is considered as the enthesis area, is similar to the patients with PsA in patients with ax-SpA, especially in the fourth and fifth fingers compared to the control group. On the other hand, almost no structural changes in nail plates were observed in patients with ax-SpA group.