Leeds Enthesitis Index Research Articles

Relationship Between Ultrasound and Physical Examination in the Assessment of Enthesitis in Patients With Spondyloarthritis: Results From the DEUS Multicenter Study.

The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis

Objectives: Enthesitis is considered a hallmark of psoriatic arthritis (PsA). The objective was to assess clinical enthesitis in PsA including its prevalence in different contexts, scores used and consequences of enthesitis.Methods: A systematic literature review with meta-analysis was conducted in PubMed 2010-2023, focusing on manuscripts involving adult PsA patients and reporting information related to enthesitis. Data collected included the prevalence of clinical enthesitis (i.e., number of patients with at least one enthesitis); scores used: Leeds Enthesitis Index (LEI), MASES, SPARCC; and impact of enthesitis on disease activity, patient-reported outcomes and use of analgesics. Univariate random-effects meta-analysis was applied for pooling percentages and means.Results: Overall, 212 studies, i.e., 84,262 PsA patients were analyzed. The pooled prevalence of enthesitis in the overall population was 41.6% [95% confidence interval, 37.4-45.8]; with 67.2% [62.0-72.6] in trials and 27.8% [24.5-31.2] in observational studies. The number of enthesitis varied according to the score used, with the lowest observed for the LEI which was the most widely-used score (63.7%). Patients with enthesitis had higher disease activity and disease burden in comparison with those without enthesitis.Conclusion: Enthesitis is a frequent manifestation in PsA, concerning close to half the patients, and is more prevalent in trials than in observational studies, reflecting recruitment patterns. The clinical assessment of enthesitis remains challenging, with heterogeneity in the scores used influencing the results: the most used score was the LEI which also led to the lowest prevalence of enthesitis. Links with patients’ quality of life should be further explored.

Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast. Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis. Amgen.

The Development and Validation of a Novel Training Infographic for the Physician Global Visual Analog Scale in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a heterogenous condition with musculoskeletal and skin manifestations. The physician global visual analog scale (VAS) is an important component of many composite scores used in clinical trials and observational studies. Currently, no training material exists to standardize this assessment. The Psoriatic Arthritis Validation of Physician Global VAS (PAVLOVAS) project describes the development of a novel training infographic with stakeholder involvement, which was then evaluated in a Latin square design in which 20 patients with PsA were assessed by 10 clinicians. For each group of 10 patients, 5 assessors conducted traditional assessment (consisting of 66/68-joint count, body surface area, Leeds Enthesitis Index, and dactylitis and nail counts) and 5 assessors conducted a standardized, thorough general examination informed by the infographic. Assessors switched assessment type between groups. The 3-item (3VAS) and 4VAS informed by traditional and infographic methods were compared, alongside other composite scores. There was strong agreement between traditional and infographic physician global VAS (intraclass correlation coefficient [ICC] 0.69, P = 0.01). This improved to very strong agreement when incorporated into the 3VAS (ICC 0.99, P < 0.001) and 4VAS (ICC 0.99, P < 0.001). The duration of assessment was significantly less for the infographic vs traditional groups (6.5 vs 7.8 mins, P < 0.001). There was moderately high agreement between the 3VAS and 4VAS categories of disease activity, with the same categories defined by Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA; Ⲭ2 17.0, P = 0.049). Our group developed and validated a novel training infographic that informs a briefer assessment of the physician global VAS than traditional assessments. This tool has potential applications in training and routine clinical practice.

Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials.

The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA. This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue. Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52. Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis. NCT03675308, and NCT03671148.

P101 Investigating the association between clinical enthesitis and central sensitisation in psoriatic arthritis

Abstract Background/Aims Psoriatic Arthritis (PsA) is an inflammatory arthritis with enthesitis as its characteristic clinical feature. Enthesitis can be clinically challenging to differentiate from the widespread pain associated with Fibromyalgia (FM), the prototype of central sensitisation (CS) present in up to 30% of PsA patients. Algometry is used in CS research to quantify pressure pain threshold (PPT), reflecting increased pain sensitivity when reduced. Ultrasound is a valuable tool to evidence entheseal inflammatory changes in PsA. This study investigates associations between CS, i.e., FM, and entheseal ultrasound outcomes to better characterise pain mechanisms in PsA enthesitis. Methods A total of 20 patients with active PsA about to start a new immunosuppressant were recruited. Ultrasound evaluation of non-dominant knee (left for all patients) using dynamic B-mode and power Doppler was performed alongside the Leeds Enthesitis Index (LEI) collection to assess enthesitis. PPT was measured with algometry at the non-dominant knee (enthesitis), trapezius and calf muscle (CS areas), and collection of the ACR 2011 FM criteria was used to determine the presence of CS. Non-dominant areas were selected because they are less likely to exhibit biomechanical ultrasound alterations; moreover, the non-dominant side is generally more sensitive than the dominant side, thus enabling more precise PPT measurements. Correlations and t-tests were used to test associations between variables collected. SPSS was used to analyse the data. Results The 30% of patients met the FM criteria and presented higher LEI scores and lower PPT evoked threshold than FM-negative patients. Total FM scores significantly correlated with LEI scores (r = 0.69, p &amp;lt; 0.001) and calf PPTs (r=-0.53, p=-0.014), but not with knee and trapezius PPTs (r=-0.49, p = 0.09; r=-0.30, p = 0.19), or US enthesitis (r=-0.04, p = 0.86). PPTs in the areas investigated did not show significant correlations with US enthesitis, while an indirect association was observed between LEI with calf PPT (r=-0.51, p = 0.02) and trapezius PPT (r=-0.41, p = 0.06). No significant correlation was demonstrated between LEI and left knee enthesitis (r=-0.32, p = 0.17). Conclusion FM is frequent in PsA and can mimic entheseal pain, as suggested by the strong correlation with the LEI scores. In our cohort, LEI scores did not efficiently capture inflammatory enthesitis, demonstrated by the lack of association with ultrasound data. Moreover, the association between objective measurement of CS, including calf and trapezius PPTs, supports that LEI score may primarily reflect the presence of central sensitisation rather than inflammation. Therefore, relying solely on clinical detection of enthesitis may result in inappropriate treatment escalation. Ultrasound, conversely, serves as a dependable tool for confirming enthesitis and providing valuable information for making informed treatment decisions. Disclosure N.M. Aldehmi: None. N. Basu: None. J. Dale: None. A. Najm: None. F. Sunzini: None.

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

BackgroundEnthesopathy 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 workTo measure MPV, RDW, and NLR in psoriatic enthesopathy and determine their relationship to disease activity and MSUS findings.Patients and methodsThis 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.ResultsThere 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.ConclusionMonitoring 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.

Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Autoimmune thyroiditis in psoriatic disease

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients.

Efficacy and safety of tofacitinib for chronic plaque psoriasis and psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials.

To summarize and analyze the results of published randomized controlled trials of tofacitinib for the treatment of chronic plaque psoriasis and psoriatic arthritis(PsA) and discuss its efficacy and safety. An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software. A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician's Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA). A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug's long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events,and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer's disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.

BASDAI versus ASDAS in evaluating axial involvement in patients with psoriatic arthritis: a pooled analysis of two phase 3 studies.

In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0-10 scale) were analysed with mixed models for repeated measures. At baseline in the axPsA (n = 312) and non-axPsA (n = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18-0.20), tender joint count (0.12-0.29), LEI (-0.04 to 0.24) and physician global assessment (0.35-0.43); moderate correlation with fatigue (both -0.56); and strong correlation with patient global assessment of disease activity (0.62-0.69) and patient-reported pain (0.66-0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all β ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (β ≤ 0.06)/LEI (β ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

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

ObjectivesTo 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.MethodsEnthesitis 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.ResultsGuselkumab-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).ConclusionIn 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 registrationClinicalTrials.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.

Assessment of Patient-Physician Interactions in Psoriatic Arthritis: National Results of the ASSIST Study.

An overarching principle for the management of psoriatic arthritis (PsA) is a shared decision-making process between physicians and patients. The aim of this study is to assess the patient-physician relationship in a group of patients with PsA, by using the Perceived Efficacy in Patient-Physician Interactions (PEPPI) and CollaboRATE instruments. This is a cross-sectional multicenter study where consecutive patients with PsA were enrolled. For each patient, the main demographic, comorbid conditions, and clinical data were collected, including the assessment of disease activity, function, quality of life, and impact of disease. PEPPI and CollaboRATE questionnaires were used, respectively, to evaluate the patient's perception of the patient-physician relationship and the shared decision-making process. A total of 81 patients with PsA were enrolled at four centers in Italy. Overall, our patients showed a high level of confidence in obtaining needed health care, with relatively high median (IQR) values of PEPPI (20; 16-23), and a good shared decision-making process, with high median (IQR) values of CollaboRATE questionnaire (7; 6-9). PEPPI and CollaboRATE scores showed a statistically significant inverse correlation with different clinical variables such as disease duration, Leeds Enthesitis Index, PsA impact of Disease, Health Assessment Questionnaire, pain, patient's global assessment of disease activity and clinical disease activity for PsA. The presence of comorbidities did not appear to be associated with lower values of PEPPI and CollaboRATE. In this study, few patients with PsA were at risk of suboptimal communication with their physician. This phenomenon appeared to be primarily related to higher disease activity and burden.

Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2 trials.

To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with PsA from the SELECT-PsA Phase 3 trials. Patients with an inadequate response/intolerance to one or more non-biologic DMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution and protection from enthesitis development through week 56. Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in >80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. ClinicalTrials.gov identifiers: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulinG1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR1.760, 95%CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR1.827, 95%CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95%CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95%CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95%CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95%CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR0.76, 95%CI 0.45-1.28, P = 0.31; RR0.99, 95%CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR1.10, 95%CI 0.63-1.94, P = 0.73). Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. Retrospectively registered (CRD42023451894, 16 August 2023).

Identification of the Minimal Disease Activity Domains Achieved Based on Different Treatments in Psoriatic Arthritis.

The aim of this work is to characterize which Minimal Disease Activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and thedifferent treatment groups was assessed. We conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age ≥ 18years, PsA diagnosis, stable treatment for at least 6months. Patients were grouped depending on the therapy: group 1: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), group 3: Tumor Necrosis Factorα inhibitors (TNFi), group 4: interleukininhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement. A total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area ≤ 3, swollen joint count ≤ 1 and Leeds Enthesitis Index ≤ 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) ≤ 2cm and pain on visual analogue scale ≤ 1.5cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4. In each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need. Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.

Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study. This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA). A total of 296 patients with baseline data and 192 with completed week24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week24 (95%CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified. The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice. ClinicalTrials.gov identifier, NCT04758117.

The Role of Chitinase-3-Like Protein 1(YKL-40) as a Biomarker of Psoriatic Arthritis

Background Psoriatic arthritis (PsA) is a chronic multifaceted inflammatory seronegative arthritis. Plasma YKL-40 is an inflammatory biomarker. Objective To evaluate the role of Chitinase-3-like protein 1 (YKL-40) as a diagnostic biomarker in psoriatic arthritis (PsA) patients and determine its value in assessment of disease activity and severity in PsA patients. Patients and Methods This study included twenty five adult patients with clinical evidence of PsA and twenty five healthy matched age and sex as control group. All underwent history, laboratory investigation, clinical examination, assessment of disease activity using Disease Activity in PSoriatic Arthritis (DAPSA) Score and assessment of severity of PsA using Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Leeds Enthesitis Index (LEI) and examination of dactylitis. Results The mean age of patients was 39.72 ± 11.94. Also, The mean age of healthy controls was 42.88 ± 12.11. There was highly statistically significant difference regarding the serum levels of YKL- 40 (P &amp;lt; 0.01) between the patients and the control groups (P &amp;lt; 0.01). The receiver operating characteristic curve (ROC) curve of YKL -40 showed that the sensitivity and the specificity of YKL- 40 in diagnosis of PsA were 96% and 92% respectively. There were statistically significant positive correlations between YKL- 40 levels (μl/mL) and each of PASI score (p = 0.005) (r = 0.539) and DAPSA score (p = 0.007) (r = 0.526). Conclusion YKL- 40 measurement may serve as a diagnostic biomarker for PsA, as it has the potential to contribute to the fundamental processes underlying the pathogenesis of PsA. So, the results of this study suggested that the addition of YKL- 40 as a serological marker has a valuable role in diagnosis of PsA and reflection of disease activity.

Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA.MethodsData were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression.ResultsSeven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0–4.4 and 1.3–9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0–0.4 and -3.5–0.2) vs placebo (-‍0.9–‍0.4 and -1.5–1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores.ConclusionTofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.Trial registrationNCT01877668;NCT01882439.

The burden of entheseal involvement in systemic lupus erythematosus: a comparative ultrasonograghic study

BackgroundImaging is crucial for identifying and diagnosis of the musculoskeletal (MSK) symptoms, which are one of the most typical manifestations of systemic lupus erythematosus (SLE). For the joints, tendons, and entheseal sites, ultrasonography has shown to be sensitive and accurate for the diagnosis of both inflammation and structural damage.AimThe goal of the current investigation is to determine the prevalence and the distribution of entheseal abnormalities in SLE patients, using musculoskeletal ultrasonography (MSUS) and to assess the relationship between entheseal sonographic changes and the SLE disease activity.Patients and methodsOne hundred sixty-eight subjects were studied (56 SLE patients, 56 psoriatic arthritis (PSA) patients, and 56 normal cases). To compare the frequency and the distribution of entheseal involvement, high-resolution MSUS was conducted to assess the entheseal sites of all patients in accordance with the Madrid Sonographic Enthesitis Index (MASEI).ResultsClinical enthesitis was detected in 39.3% of the SLE patients using the Leeds Enthesitis Index compared to 71% detected via US examination, indicating a high proportion of subclinical enthesitis in our SLE patients. The most frequently affected enthesis was the distal insertion of the patellar tendon at the tibial tuberosity which was detected in 41% of SLE patients. Enthesitis was significantly more frequent in PSA patients (100%) compared to SLE patients (71.4%) (p < 0.05) and more significantly frequent in SLE patients compared to the healthy controls (19.6%). There was a significant correlation between MASI and SLEDAI scores (r = 0.250*, p = 0.048) and the total protein in 24 h (r = 0.289*, p = 0.031). In addition, there was an inverse significant correlation between MASEI and serum albumin (r = − 0.324*, p = 0.015).ConclusionIn SLE patients, enthesitis is frequently clinical and ultrasound-verified. The most impacted enthesis is at the insertion of the quadriceps tendon. Enthesitis presence and the rise in the MASI score can serve as indicators of the severity of the SLE disease.Key Points• The most impacted entheseal site lies at the insertion of the quadriceps tendon.• The presence and the rise in MASEI score can serve as indicators of the severity of the SLE disease.