Effects of cytotoxic T-lymphocyte-associated protein 4 compared to TNF inhibitors on lipid profile: Results from an observational multicentre rheumatoid arthritis cohort.

AIM: To evaluate the impact of selective cytotoxic T-lymphocyte-associated protein 4 (CTLA-4Ig) compared to tumor necrosis factor inhibitors (TNFi) on cardiovascular (CV) clinical and laboratory outcomes in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational multicenter study of RA patients included in the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group database, collecting demographic, clinical, and laboratory data of those starting a CTLA-4Ig or TNFi at baseline, 6-month, and 12-month follow-up. RESULTS: Of the 206 RA patients without previous CV events enrolled in the study, 64 received a CTLA-4Ig and 142 a TNFi. The two groups did not differ in age, gender, or smoking habits, and the prevalence of hypertension, diabetes, and metabolic syndrome was similar. Over a follow-up period of 12 months, although no significant differences were found in the disease activity course, we observed that LDL cholesterol levels slightly decreased only in the CTLA-4Ig-treated patients. CONCLUSIONS: Patients treated with both CTLA-4Ig and TNFi did not differ in disease activity response and changes in traditional CV risk factors after 12 months of treatment. However, CTL-A-4Ig treatment is associated with a favorable change in lipid profile at 12-month follow-up.

Defining anti-synthetase syndrome: a systematic literature review.

OBJECTIVES: Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. METHODS: We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. RESULTS: We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. CONCLUSIONS: The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

Predictors, Risk Factors, and Incidence Rates of Psoriatic Arthritis Development in Psoriasis Patients: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Agreement on how to identify psoriasis (PsO) patients at risk of developing psoriatic arthritis (PsA) is lacking. OBJECTIVE: To identify predictors, risk factors and incidence rate (IR) of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA). METHODS: MEDLINE, Embase, and Cochrane databases were searched. Cohort studies were used to assess the predictors, while case-control studies for PsA risk factor determination. RESULTS: We screened 4698 articles for eligibility, and 110 underwent a full reading and 26 were finally included. Among skin and nail phenotypes, PsO severity and nail pitting were selected as predictors of PsA development. Furthermore, PsO patients with arthralgia (pooled RR 2.15 [1.16; 3.99]) and/or with imaging-MSK inflammation (pooled RR 3.72 [2.12; 6.51]) were at high risk of PsA. Higher categories of BMI and a family history of PsA were other predictors. In outpatient-based cohort studies, the IR of PsA per 100 patient-years varied from 1.34 to 17.4. LIMITATIONS: Despite the strength of the overall results, the heterogeneity and the number of the cohort studies could be considered a limitation. CONCLUSIONS: This study provides a tentative profile of the PsO patient at risk of PsA and will help the design of PsA prevention trials.

In Patients with Early Peripheral Psoriatic Arthritis Baseline C-Reactive Protein, Pain and Ultrasound-Detected Synovitis Predict Subsequent Treatment with ts/bDMARDs. A Retrospective Analysis.

With the availability of effective treatment with targeted synthetic and biologic disease-modifying anti-rheumatic drugs (ts/bDMARDs) for psoriatic arthritis (PsA), it is crucial to identify predictors of access to this treatment since disease onset. We retrospectively enrolled patients with peripheral PsA, assessed in an early arthritis clinic from 2005 to 2020. The main baseline demographic, clinical and ultrasonographic (assessment of bilateral wrist and metacarpophalangeal joints) features were evaluated through descriptive statistics and tested as predictors by univariate and multivariate Cox models. The outcome of interest was the indication for ts/bDMARDs within 2 years from diagnosis. We included 238 patients with PsA, with a mean (sd) age of 51.04 (13.98) years; 90 (37.8%) were male, and the median (IQR) symptom duration was 6.12 (3.29-12.25) months. In univariate analyses, C-reactive protein (RR, 95% CI 1.204 (1.065,1.362)), Visual Analogue Scale (VAS) pain (1.027 (1.005,1.048)), the number of tender joints on 28 joints (1.087 (1.025, 1.153)), and a synovial power Doppler (PD) score > 1 (3.63 (1.307, 10.08)) emerged as significant predictors. C-reactive protein, VAS pain and PD confirmed their predictive value also in multivariate models. These results provide preliminary evidence on the features that might characterize patients with early peripheral PsA requiring more intensive monitoring and treatment escalation.

Sensitivity to change and clinical correlations of the novel DACtylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVE: The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. METHODS: Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). RESULTS: We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P < 0.001) and between clinical remission and non-remission groups (P < 0.001). CONCLUSION: The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

Novel and reliable DACTylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVES: Dactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score. METHODS: After a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score. RESULTS: DACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score. CONCLUSIONS: The novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review.

Background: Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. Methods: In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. Results: For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Conclusions: Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.

Transition phase towards psoriatic arthritis: clinical and ultrasonographic characterisation of psoriatic arthralgia.

Objective: Non-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition. Methods: A cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development. Results: Tenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, p<0.001), although synovitis and enthesitis were numerically more frequent in PsOAr. Five patients in PsOAr and one in PsO group developed PsA, with an incidence rate of 109.2/1000 person-years in PsOAr vs 13.4/1000 person-years in PsO (p=0.03). Visual Analogue Scale pain, Health Assessment Questionnaire, joint tenderness and US active enthesitis were baseline variables associated with PsA development. Conclusion: Tenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.

Serum calprotectin as a marker of ultrasound-detected synovitis in early psoriatic and rheumatoid arthritis: results from a cross-sectional retrospective study.

OBJECTIVES: We aimed to evaluate the correlation between serum calprotectin and clinical and ultrasonographic (US) variables in early-onset psoriatic arthritis (PsA) and controls with rheumatoid arthritis (RA). METHODS: In a retrospective cross-sectional study, including PsA and matched RA patients, 44 joint counts (TJC, SJC), calprotectin, ESR and CRP were measured. US of wrists and MCPs 1-5 was performed, with grey-scale (GS) and power Doppler (PD) scored 0-3 at each site, summed in a total score. The correlation between calprotectin, clinical and US variables was evaluated by Spearman's coefficient, the predictivity by calprotectin of US by regression. Secondary analyses separating polyarticular PsA and using different US definitions (GS>1, PD>1) were performed. RESULTS: 78 PsA and 78 RA were included (PsA male 32%; mean age 51.7 (13.5)). Calprotectin did not significantly differ in PsA and RA. In PsA, calprotectin correlated with GS score (ρ=0.340, p=0.008), PD score (ρ=0.292, p=0.023) and the presence of PD (ρ=0.263, p=0.042); in RA there were no significant correlations. In polyarticular PsA, a significant correlation between calprotectin and GS (ρ=0.369, p=0.019) and PD scores (ρ=0.363, p=0.021) was confirmed. In both PsA and RA, calprotectin and CRP significantly correlated, while SJC and TJC did not. In the regression analysis, calprotectin did not predict US variables in PsA. Similar results were achieved in RA. CONCLUSIONS: In early PsA, serum calprotectin correlates with US measures of disease activity. Our results provide preliminary evidence for the application of this biomarker in early PsA.

Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology.

OBJECTIVES: The purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with tamoxifen. METHODS: Data were collected from the administrative healthcare database of Lombardy Region, Italy, from 2004 to 2013. This study follows a nested cohort design, including women with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole, exemestane or letrozole. The risk of RA related to the prescription of the different drugs was estimated by survival models for competing risks and the results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CI), adjusted for age and cancer severity. RESULTS: Out of total 10 493 women with breast cancer with a median (IQR) age of 66 (57-74), 7533 (71.8%) started an active treatment with AIs or tamoxifen. In this subgroup a total of 113 new cases of RA developed during the 26 105.9 person-year of 10 186 exposure periods, including time varying exposures in the same patient. Using tamoxifen as reference category, AIs therapy was associated with an increased risk of RA (adjusted HR 1.62 (95%1.03-2.56)), in particular in patients receiving anastrozole, even after adjusting for age and level of neoplasia: (adjusted HR 1.75 (95%1.07-2.86)). CONCLUSIONS: In a large population-based sample of women with breast cancer, exposure to AIs compared with tamoxifen is associated with a significantly increased risk of RA, which is not influenced by the cancer severity and the relationship of age with indication to specific drugs.

Musculoskeletal ultrasonography for psoriatic arthritis and psoriasis patients: a systematic literature review.

Objective: To systematically review the role of musculoskeletal US in patients suffering from PsA or psoriasis (Pso) in terms of prevalence, diagnosis, prognosis, monitoring and treatment. Methods: A systematic literature review was conducted through medical databases (MEDLINE via PubMed, Embase) and the grey literature up to September 2015 to inform a new study of the Musculoskeletal Ultrasound Study Group of the Italian Society for Rheumatology. All articles reporting data on musculoskeletal US in PsA or Pso were included and extracted according to the underlying clinical question. Results: A total of 86 publications were included. The prevalence of US abnormalities showed a wide range for each examined feature (e.g. 37-95% for entheses thickness of the lower limbs). The performance of US for diagnosis of disease or elementary lesions was variable across studies, but no study evaluated the overall performance of US in addition to clinical findings for diagnosing PsA. Considering US in defining PsA and Pso prognosis, several works focused on US of entheses of lower limbs in Pso, while for the monitoring of PsA activity five different scoring systems were identified. Last, the results of the role of US in guiding intra-articular interventions were controversial for the clinical outcomes, but in favour of US for accuracy. Conclusion: despite the recognized importance of US in the management of PsA and Pso, this review clearly demonstrated the need of pivotal research in order to optimize the use of US in the diagnosis and monitoring of psoriatic disease.

Cardiovascular Comorbidities Relate More than Others with Disease Activity in Rheumatoid Arthritis.

OBJECTIVES: To explore the influence of comorbidities on clinical outcomes and disease activity in rheumatoid arthritis (RA). METHODS: In patients included in the cross-sectional observational multicenter international study COMORA, demographics, disease characteristics and comorbidities (hypertension, diabetes, hyperlipidemia, renal failure, ischemic heart disease, stroke, cancer, gastro-intestinal ulcers, hepatitis, depression, chronic pulmonary disease, obesity) were collected. Multivariable linear regression models explored the relationship between each comorbidity and disease activity measures: 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR), patient's and physician's global assessment (PtGA, PhGA), patient reported fatigue and 28-Disease Activity Score (DAS28). Results are expressed as mean difference (MD) adjusted for the main confounders (age, gender, disease characteristics and treatment). RESULTS: A total of 3,920 patients were included: age (mean ±SD) 56.27 ±13.03 yrs, female 81.65%, disease duration median 7.08 yrs (IQR 2.97-13.27), DAS28 (mean ±SD) 3.74 ± 1.55. Patients with diabetes had more swollen and tender joints and worse PtGA and PhGA (MD +1.06, +0.93, +0.53 and +0.54, respectively). Patients with hyperlipidemia had a lower number of swollen and tender joints, lower ESR and better PtGA and PhGA (MD -0.77, -0.56, -3.56, -0.31 and -0.35, respectively). Patients with history of ischemic heart disease and obese patients had more tender joints (MD +1.27 and +1.07) and higher ESR levels (MD +5.64 and +5.20). DAS28 is influenced exclusively by cardiovascular comorbidities, in particular diabetes, hyperlipidemia, ischemic heart disease and obesity. CONCLUSIONS: Cardiovascular comorbidities relate more than others with disease activity in RA. Diabetes and hyperlipidemia in particular seem associated with higher and lower disease activity respectively influencing almost all considered outcomes, suggesting a special importance of this pattern of comorbidities in disease activity assessment and clinical management.

Ultrasound imaging for the rheumatologist XLV. Ultrasound of the shoulder in psoriatic arthritis.

OBJECTIVES: The aims of this study were to investigate the prevalence of ultrasound (US) pathologic abnormalities in the shoulders of psoriatic arthritis (PsA) patients and to compare them with the main clinical findings. METHODS: Ninety-seven PsA patients were enrolled in the study. The subacromial/subdeltoid bursa, the sheath of the long biceps tendon, the glenohumeral joint and the acromion-clavicular joint were examined for the presence of synovial effusions and synovial hypertrophy. Rotator cuff tendons (supraspinatus, subscapularis, infraspinatus) were imaged for tendinosis, calcifications and total or partial tears, while deltoid enthesis were evaluated for local enthesitis and the lesser and greater tuberosity of the humerus for the presence of enthesophytes. RESULTS: Tendinosis represented the most frequent abnormal finding. Supraspinatus tendinosis was detected more often than subscapularis and infraspinatus tendinosis. When considering tendon tear, supraspinatus was also the most frequently involved anatomical structure. Clinical examination frequently failed to detect abnormalities in patients in whom US examination showed pathological findings. This is particularly true for tendon involvement, i.e. effusion within the sheath of the biceps tendon was imaged in 43 shoulders but clinical assessment reported abnormalities only in 22 shoulders (p<0.0001). CONCLUSIONS: US examination appears to be a useful and sensitive imaging technique, specifically in identifying joint and tendon involvement of the shoulder.

Ultrasound imaging for the rheumatologist. XLII. Assessment of hip pain in rheumatic patients: the radiologist's view.

Hip pain is a common complaint in daily practice and the identification of the underlying pathologic condition is the first step for an adequate treatment. In this review, we discuss the available evidence for the application of conventional radiography, computed tomography and magnetic resonance imaging in rheumatologic patients with painful hip, presenting the main imaging findings due to osteoarthritis, inflammatory arthritis (rheumatoid arthritis and spondyloarthritides), osteonecrosis and some other soft tissue involvement (bursitis and synovial cyst) that could be the cause of hip pain. Because different imaging techniques show different sensitivity and specificity, the choice of technique to use depends on the type and stage of the disease itself.

Ultrasound imaging for the rheumatologist XXXVIII. Sonographic assessment of the hip in psoriatic arthritis patients.

OBJECTIVES: The aims of our study were to investigate the prevalence of ultrasound (US) pathological abnormalities in the hip of psoriatic arthritis (PsA) patients and compare them with the clinical findings. METHODS: Sixty-five PsA patients were enrolled in the study. Bilateral examination of the hip was performed to detect joint effusion, synovial hypertrophy, irregularity of femoral head and neck profile as seen in erosions and/or osteophytes. RESULTS: Joint effusion was detected in 20 out of 130 hips (15%). Synovial hypertrophy was present in 12 out of 20 hips (60%) associated with effusion (9.3% of all hip joints) and only 1 of them showed PD signal. Small effusion without synovial proliferation was imaged in 8 out of 20 hips (40%). On the whole 14 out of 65 patients (21%) had joint effusion with or without synovial hypertrophy using US. No erosions of the femoral head and neck profile were detected whilst osteophytes were imaged in 27 joints (20%). No US abnormalities were demonstrated in 18 hips with pain/tenderness on physical examination, whilst joint effusion was seen in 8 joints which were asymptomatic. CONCLUSIONS: US is a useful imaging method to evaluate hip involvement in PsA that could be integrated into routine PsA management even if patients do not complain of hip involvement.