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.

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.

Detection of subclinical enthesitis by ultrasonography in patients with psoriasis and controls.

INTRODUCTION: Psoriasis is a widespread chronic inflammatory skin disease; enthesitis is inflammation of the tendon, ligament, and joint capsule insertion, prevalent in patients with psoriatic arthritis. OBJECTIVES: The aim of study to evaluate the utility of the Madrid Sonography Enthesitis Index scoring system for accurate detection of subclinical enthesitis in patients with Psoriasis compared with healthy controls. Another objective was to assess increase in enthesis area and Psoriatic arthritis incidence, in a prospective 1-year follow-up. METHOD: Patients aged ≥18 years who were diagnosed with Psoriasis, without musculoskeletal complaints, and who did not have any clinical sign and/or symptom of enthesitis and synovitis were included in the study. The patients and healthy controls were evaluated with ultrasonography. Ultrasonography evaluation consisted of the detection of gray-scale enthesitis and power Doppler signal in the enthesis areas. The Madrid Sonography Enthesitis Index scoring system was used to quantify the extent of the sonographic enthesis abnormalities. RESULTS: The mean MASEI score, structure, thickness, erosion, and calcification were significantly higher in the Psoriasis group than in the control group. The mean MASEI score, structure, erosion, and calcification measurements were significantly higher at the last examination when compared to the first examination. The triceps was the most commonly affected tendon in both groups. CONCLUSION: Ultrasonography is an important tool for diagnosis and follow-up of subclinical enthesitis in patients with psoriasis. Regardless of disease duration and severity, patients should be screened using ultrasonography at yearly intervals.

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy / DKK-1 en artritis psoriásica: correlación con la actividad de la enfermedad y la entesopatía

Background: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. Objectives: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. Methods: This observational case–control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. Results: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). Conclusions: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.(AU)

Antecedentes: La artritis psoriásica (APs) es una enfermedad inflamatoria compleja con características clínicas variadas. Una característica patognomónica de la artritis psoriásica es la entesitis. La inflamación entesófila finalmente conduce a la producción de hueso nuevo (entesófitos). La proteína 1 relacionada con dickkopf (DKK-1) es un inhibidor sin alas (Wnt) que inhibe la función de los osteoblastos. Objetivos: Evaluación del nivel sérico de DKK-1 y su asociación con la actividad de la enfermedad y la entesopatía en pacientes con APs. Métodos: Este estudio observacional de casos y controles; incluyó a 50 pacientes con artritis psoriásica y 50 voluntarios sanos emparejados por edad y sexo. Todos los participantes fueron sometidos a historia clínica completa, evaluación clínica, actividad de APs utilizando la puntuación del Índice de Actividad de la Enfermedad para la Artritis Psoriásica (DAPSA), la gravedad y la extensión de la psoriasis fueron determinadas por el área de psoriasis y el índice de gravedad (PASI). La evaluación ultrasonográfica de las entesis se realizó de acuerdo con el índice de entesitis sonográfica de Madrid (MASEI). Se evaluó el nivel sérico de DKK-1 y la correlación con la actividad de la enfermedad y la entesopatía en pacientes con artritis psoriásica. Resultados: No hubo diferencias significativas entre los pacientes y los controles con respecto a la edad y el sexo. El valor medio del índice SPARCC, la puntuación DAPSA y la puntuación PASI fueron 6,74±4,58, 33,24±15,26 y 8,35±10,93 respectivamente. Hubo diferencia significativa entre pacientes y controles con respecto a los niveles séricos de DKK-1 y la puntuación MASEI (p <0,0001). Hubo correlación positiva significativa entre DKK-1 sérico y MASEI (r: 0,43527, p = 0,00158), y daño MASEI (r: 0.38384, p = 0,00593). Conclusiones: Los niveles séricos de DKK-1 se elevaron en pacientes con APs y se encontró que estaban correlacionados con la puntuación MASEI para la entesopatía.(AU)

DKK-1 in psoriatic arthritis: Correlation with disease activity and enthesopathy.

BACKGROUND: Psoriatic arthritis (PsA) is a complex inflammatory disease with varied clinical characteristics. A pathognomonic characteristic of PsA is enthesitis. Entheseal inflammation ultimately leads to the production of new bone (enthesophytes). Dickkopf-related protein-1 (DKK-1) is a wingless (Wnt) inhibitor that inhibits osteoblast function. OBJECTIVES: Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients. METHODS: This observational case-control study included 50 PsA patients and 50 healthy volunteers matched for age and gender. All participants were subjected to full medical history, clinical assessment, PSA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index (PASI). Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index (MASEI). Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed. RESULTS: There was no significant difference between patients and controls regarding age and sex. The mean value of SPARCC index, DAPSA score and PASI score were 6.74±4.58, 33.24±15.26, and 8.35±10.93, respectively. There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score (p<0.0001). There was a significant positive correlation between serum DKK-1 and MASEI (r: 0.43527, p: 0.00158), MASEI inflammatory (r: 0.37958, p: 0.00655), and MASEI damage (r: 0.38384, p: 0.00593). CONCLUSIONS: Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy.

Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.

The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

OBJECTIVES: To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. METHODS: Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. RESULTS: A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. CONCLUSIONS: Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

A prospective survey on therapeutic inertia in psoriatic arthritis (OPTI'PsA).

OBJECTIVES: Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA). METHODS: Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases ('oligoarthritis', 'enthesitis', 'polyarthritis', 'neoplastic history', 'cardiovascular risk') requiring treatment OPTImization, and two 'control' cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment-according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA. RESULTS: One hundred and one rheumatologists completed this OPTI'PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were 'oligoarthritis' and 'enthesitis' with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty ('polyarthritis in relapse', 'neoplastic history' and 'cardiovascular risk') generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment. CONCLUSION: The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia.

Hereditary Hypophosphatemic Rickets with Hypercalciuria Presenting with Enthesopathy, Renal Cysts, and High Serum c-Terminal FGF23: Single-Center Experience and Systematic Review.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH)2D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification.

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

BACKGROUND: Imaging 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. AIM: The 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 METHODS: One 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). RESULTS: Clinical 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). CONCLUSION: In 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.

The posterolateral ligament of the elbow: anatomy and clinical relevance.

BACKGROUND: The posterolateral capsule was recognized in the past as an important structure for elbow stability but was later disregarded. Two recent biomechanical studies demonstrated its role in preventing posterolateral instability, and thus it should be identified as a distinct ligament: the posterolateral ligament (PLL). This study includes 2 parts: an anatomic study of the PLL's footprint and a collection of 5 cases of pathologic lesions of the PLL. METHODS: Six cadaveric upper limbs were assessed. The attachments of the PLL were dissected, the footprints were marked and photographed, and the 2-dimensional area and length were measured. RESULTS: The mean proximal attachment dimensions were a length of 13 mm and an area of 101 mm2, and the mean distal attachment dimensions were 19 mm and 111 mm2, respectively. There were 2 cases of posterolateral elbow pain in professional cricket bowlers, diagnosed radiographically as enthesopathy of the PLL's proximal attachment on the posterior capitellum, probably due to repeated forced hyperextension of the elbow. Both patients were treated by débridement of the posterior capitellum and reattachment of the PLL, with complete resolution of symptoms. In addition, there were 3 cases of clinical posterolateral rotatory instability in young patients. Two athletes had an isolated acute tear of the PLL, and on physical examination, both had positive posterior draw test results but negative pivot-shift test results. Both underwent elbow arthroscopy and repair of the PLL with resolution of symptoms. The third patient had long-standing recurrent elbow instability, following a failed lateral ulnar collateral ligament reconstruction, in the presence of an Osborne-Cotterill lesion. He underwent revision lateral ulnar collateral ligament reconstruction, bone grafting of the bony lesion, and reattachment of the PLL, with complete resolution of symptomatic posterolateral rotatory instability. CONCLUSIONS: The PLL of the elbow has a significant role in the elbow's posterolateral stability. Its footprints were described, and its clinical significance was demonstrated in cases of elbow instability caused by acute ligament tears and elbow pain due to ligament enthesopathy. Surgeons should be aware of this structure and potential pathology related to its injury.

Demonstrating the relationship of ultrasonographic parameters with disease activity and pain in lateral epicondylitis.

To evaluate the relationship of ultrasonographic evaluation parameters with pain, muscle strength and disease severity in lateral epicondylitis (LE). 64 people were included in present retrospective, cross-sectional study. Activity and rest pain was questioned with Visual Analog Scale (VAS). Also, Patient Rated Tennis Elbow Evaluation (PRTEE) and the maximum grip strength were evaluated. Hypoechoic region, neovascularity, cortical irregularity, enthesopathy and peritendinous fluid or bursitis were evaluated by ultrasonography. 48 of the patients were female and 16 were male. Mean age was 48.53 ±â€…6.12, body mass index was 27.70 ±â€…4.75. 55 (85.9%) hypoechoic region, 31 (48.4%) neovascularity, 21 (32.8%) cortical irregularity, 19 (29,7%) enthesopathy, and 18 (28.1%) peritendinous fluid or bursitis were detected by ultrasonography. When the ultrasonographic findings and clinical findings of the patients were compared, no significant difference was found between the hypoechoic region, cortical irregularity, enthesopathy and clinical findings (P > .05), while the extension grip strength was found to be significantly lower in patients with neovascularity (P = .045). In addition, patients with peritendinous fluid or bursitis, were found to be significantly lower in both flexion (P = .033) and extension (P = .023) grip strength, while PRTEE function (P = .021) subgroup and total (P = .038) scores were significantly higher. Hypoechoic region, cortical irregularities and enthesopathy were not evaluated to be associated with disease severity, pain and muscle strength. Neovascularity was found to be associated only with extension grip strength. Peritendinous fluid or bursitis was found to be associated with both flexion and extension grip strength and disease activity, but not associated with pain.

Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension.

OBJECTIVES: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS). METHODS: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12. In the second period (weeks 12-24) all patients received open-label secukinumab with placebo patients switching to secukinumab (150 mg or 300 mg). The third period (weeks 24-52) was an extended open-label treatment period. The long-term responsiveness of the Global EULAR-OMERACT Synovitis Score (GLOESS), clinical enthesitis and global PDUS-detected enthesitis score (using two candidate definitions of activity) at patient level, together with clinical efficacy across key manifestations of PsA and safety were assessed. RESULTS: Of the 166 patients enrolled, 144 completed week 52. A significant reduction in GLOESS was demonstrated in the secukinumab group vs placebo at week 12, followed by a stable reduction of synovitis until week 52 in the secukinumab group while placebo switchers from week 12 reached a similar level of reduction at week 24 with stability thereafter. Likewise, a significant reduction in the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index was shown in the secukinumab group vs placebo at week 12 with sustained improvement to week 52. Global OMERACT PDUS enthesitis scores were numerically lower in secukinumab vs placebo switchers in the first two treatment periods, with some stability in the third period in both groups. Improvements in clinical responses were also observed across all key domains of PsA up to week 52 in both treatment groups with no new or unexpected safety signals. CONCLUSIONS: ULTIMATE showed consistent improvements in clinically and ultrasound-assessed synovitis and enthesitis and sustained clinical efficacy through week 52 in patients with PsA treated with secukinumab and placebo switched to secukinumab.

Predictors of persisting pain in children with Juvenile Idiopathic Arthritis: a case control study nested in the ReACCh-Out cohort.

BACKGROUND: To identify baseline predictors of persisting pain in children with Juvenile Idiopathic Arthritis (JIA), relative to patients with JIA who had similar baseline levels of pain but in whom the pain did not persist. METHODS: We used data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) inception cohort to compare cases of 'moderate persisting pain' with controls of 'moderate decreasing pain'. Moderate pain was defined as a Visual Analogue Scale (VAS) for pain measurement score of > 3.5 cm. Follow-up was minimum 3 years. Univariate and Multivariate logistic regression models ascertained baseline predictors of persisting pain. RESULTS: A total of 31 cases and 118 controls were included. Mean pain scores at baseline were 6.4 (SD 1.6) for cases and 5.9 (1.5) for controls. A greater proportion of cases than controls were females (77.4% vs 65.0%) with rheumatoid factor positive polyarthritis (12.9% vs 4.2%) or undifferentiated JIA (22.6% vs 8.5%). Oligoarthritis was less frequent in cases than controls (9.7% vs 33%). At baseline, cases had more active joints (mean of 11.4 vs 7.7) and more sites of enthesitis (4.6 vs 0.7) than controls. In the final multivariate regression model, enthesitis count at baseline (OR 1.40, CI 95% 1.19-1.76), female sex (4.14, 1.33-16.83), and the overall Quality of My Life (QoML) baseline score (0.82, 0.69-0.98) predicted development of persisting pain. CONCLUSIONS: Among newly diagnosed children with JIA with moderate pain, female sex, lower overall quality of life, and higher enthesitis counts at baseline predicted development of persisting pain. If our findings are confirmed, patients with these characteristics may be candidates for interventions to prevent development of chronic pain.

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

BACKGROUND: Tofacitinib 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. METHODS: Data 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. RESULTS: Seven 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. CONCLUSION: Tofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity. TRIAL REGISTRATION: NCT01877668;NCT01882439.

Utility of Musculoskeletal Ultrasound in Psoriatic Arthritis.

PURPOSE: Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming increasingly popular, both in clinical practice and research. This narrative reviews recent literature on the utility of ultrasound in PsA. METHODS: A search of PubMed was used to identify publications written in English, with titles containing the term psoriatic arthritis and either ultrasound, ultrasonography, or sonographic. A total of 178 publications were identified; those that were not relevant (n = 59), were not original research (n = 45), or that had small (<30) sample sizes (n = 34) were excluded, leaving 40 studies for review of the use of ultrasound in various aspects of PsA. Publications with similar findings were grouped into seven domains: (1) the use of ultrasound findings compared to clinical assessment; (2) the use of ultrasound in the assessment of enthesitis; (3) the use of ultrasound in the assessment of nails; (4) the use of ultrasound as a screening tool in patients with psoriasis at risk for PsA; (5) the use of ultrasound in differentiating PsA from other similar conditions; (6) the use of ultrasound as a measure of disease activity; and (7) the use of ultrasound compared to MRI. FINDINGS: In recent studies, ultrasound measures of inflammation tended to agree with objective clinical findings of disease, such as swollen joint counts, while being less influenced by subjective measures, such as pain. Ultrasound has utility in the assessment of enthesitis and psoriatic nail disease in PsA, and as an overall measure of disease activity. Ultrasound-based outcomes measures have been used in observational studies and in clinical trials involving PsA, and may have utility as a measure of treatment response. The findings from recent studies suggest that ultrasound may have utility in improving the accuracy and precision of screening programs designed to identify subclinical PsA in cohorts of patients with psoriasis; however, cost-efficacy remains to be determined. Beyond screening, ultrasound may have utility in the diagnosis of PsA in patients with suspected inflammatory arthritis, and ultrasound measures of inflammation agree with MRI measures of inflammation, meaning that incorporating ultrasound into clinical practice might help to overcome the barriers associated with MRI. IMPLICATIONS: As ultrasound technology continues to advance, and associated costs decrease, it is likely that ultrasound will become more integrated into the clinical journeys of patients with PsA.

Clinical profile and treatment utilisation based on HLA-B*27 status in axial spondyloarthritis: results from ASAS-PerSpA study.

OBJECTIVE: We aimed to characterize differences of clinical features, extra-musculoskeletal manifestations and treatment utilizations based on the patients' HLA-B*27 status in a global axSpA cohort and identify predictors of HLA-B*27 negativity in these patients. METHODOLOGY: In post-hoc analysis of the ASAS-PerSpA study, patients fulfilling the 2009 ASAS classification criteria for axSpA and typed for HLA-B*27 were included. The patient characteristics cwere compared between the HLA-B*27(+) and HLA-B*27(-) subgroups. Multivariablete logistic regression was conducted to identify predictors of HLA-B*27 negativity. RESULTS: Of 2910 patients with axSpA from 24 countries, 2269 were tested for HLA-B*27 [1753 HLA-B*27(+) and 516 HLA-B*27(-)]. The proportion of males was higher in the HLA-B*27 (+) compared to the HLA-B*27 (-) subgroup (72.1 vs 54.3%). Patient population with HLA-B*27 (+) more often had positive family history for axSpA (29.8 vs 15.3%), and younger age at diagnosis, 31.6 years (SD 10.9) vs 37.7 years (SD 12.1). HLA-B*27 (-) patients had significantly higher peripheral arthritis (47.5 vs 42.1%, p<0.05), psoriasis (19.4 vs 10.2), enthesitis (56.6 vs 49.8%) and IBD (12.8 vs 3.4) (p<0.001). The exposure to csDMARDS in HLA-B*27 (-) patients was higher (61.2 vs 55.0%, p< 0.05). On multivariable analysis, HLA-B*27 (-) status was positively associated with enthesitis, psoriasis and IBD with an OR 1.27 (1.02-1.57), 1.84 (1.36-2.48) and 4.84 (3.23-7.30) respectively, and inversely associated with uveitis, OR 0.37 (0.27-0.50). CONCLUSION: HLA-B*27 (-) axSpA patients had a longer delay in diagnosis, more frequently had peripheral arthritis, enthesitis, IBD, psoriasis, and were more often treated with csDMARDs compared to HLA-B*27 (+) subgroup.