Clinical and subclinical atherosclerosis in patients with systemic sclerosis: an observational, multicentre study of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale).

OBJECTIVES: Conflicting results about clinical and subclinical atherosclerosis in systemic sclerosis (SSc) and the associated risk factors have been reported. Hence, we aimed to determine the prevalence of clinical and subclinical atherosclerosis in a large number of Italian SSc patients and the associated risk factors. METHODS: This study included 613 SSc patients from 11 Italian tertiary Rheumatologic Units. All patients underwent full history taking, clinical examination, and relevant laboratory and radiological investigations. Doppler ultrasonography (US) of the common carotid and upper and lower limbs was performed to measure carotid and femoral intima-media thickness (cIMT and fIMT), and carotid and peripheral atheroma plaques. Doppler US of the brachial artery was performed to measure flow-mediated dilatation (FMD). RESULTS: Patients were mostly women (91.4%) with a median age of 61 years (range, 20-100); a median disease duration of 14 years (range, 0-77) from the onset of the first non-Raynaud's phenomenon (RP); 9.3% had a history of clinical atherosclerosis (9 stable/unstable angina, 21 myocardial infarctions, 24 heart failure, 3 strokes, 8 transient ischaemic attack, 6 intermittent claudication, 10 atrial thrombo-embolism). In 37.1% of patients, subclinical atherosclerosis was detected, after excluding those with a history of clinical atherosclerosis. The prevalence of clinical and subclinical atherosclerosis was higher than that reported by the European Society of Cardiology and observational studies that enrolled Italian healthy individuals as a control group, respectively. CONCLUSIONS: A higher prevalence of clinical and subclinical atherosclerosis was detected in SSc Italian patients and correlated with traditional and SSc-related risk factors.

Role of Patrick-FABER test in detecting sacroiliitis and diagnosing spondyloarthritis in subjects with low back pain.

OBJECTIVES: To evaluate sensitivity, specificity, and predictive value of Patrick-FABER test in assessing magnetic resonance imaging (MRI) sacroiliitis and addressing the diagnosis of spondyloarthritis (SpA) in subjects with low back pain (LBP). METHODS: Subjects with LBP were consecutively enrolled. The assessors were blinded to patients' clinical, laboratory, or imaging data. All subjects underwent sacroiliac joint MRI to detect presence of sacroiliac oedema or structural changes. RESULTS: One hundred and ten subjects were included in the study [males (61.8%); median age of 45 (21-69) years; LBP duration of 78 (3-240) months]. Patrick-FABER test sign's sensitivity was 76.2% (95% CI: 60.5-87.9%), specificity was 66.2% (95% CI: 53.6-77.2%), positive predictive value (PPV) was 58.1% (95% CI: 44.1-71.3%) and negative predictive value (NPV) was 81.8% (95% CI: 69.1-90.9%) for the diagnosis of sacroiliitis, with an overall diagnostic accuracy of 70%. At the univariate and multivariate analysis, Patrick-FABER test sign was associated with inflammatory lesions of sacroiliitis at MRI and SpA diagnosis. Univariate and multivariate analysis showed an association between smoking status (p=0.01), sacroiliitis, and SpA diagnosis. The odds of having sacroiliitis was 2.7 higher in smokers (OR: 2.7; 95% CI: 1.1-7) as compared to non-smokers and 6.3 higher in those with a positive Patrick-FABER test sign (OR: 6.3; 95%CI: 2.5-15.6) as compared to those with a negative sign. CONCLUSIONS: Our study shows that Patrick-FABER test positivity could represent a useful clinical test for addressing the use of sacroiliac joints MRI and SpA diagnosis in subjects with LBP. Further, smoking habit could represent an associate anamnestic element for addressing the use of sacroiliac MRI.

Recent developments for new investigational JAK inhibitors in psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about one-third of subjects with psoriasis. Several treatment modalities targeting Janus Kinase pathways and intracellular inflammatory cascade are now available and under clinical investigation to treat this disease. AREAS COVERED: This review describes ongoing and recently completed phase 2 and 3 randomized clinical trials (RCTs) evaluating the efficacy and safety of approved JAK (Tofacitinib and Upadacitinib) and investigational JAK inhibitors (JAK1 inhibitors: Filgotinib and Ivarmacitinib (SHR0302); TYK2 inhibitors: Brepocitinib (PF-06700841) Deucravacitinib (BMS-986165), and NDI-034858) in PsA through February 2023. EXPERT OPINION: Current standard of care has significantly improved the quality of life in PsA. Recently approved JAK inhibitors for PsA have addressed many of the unmet needs of PsA, particularly of those with severe phenotypes. Preliminary results from several RCTs have reported good and fast efficacy and an acceptable safety profile of investigational JAK inhibitors in PsA. Additional clinical trials and long-term outcome data on these agents are necessary for increasing available therapeutic options for PsA.

Small molecule therapy for managing moderate to severe psoriatic arthritis.

INTRODUCTION: The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases. Areas covered: We searched in the PUBMED database and review published data on the efficacy and safety profile of the small molecules, inhibitor of phosphodiesterase 4, apremilast, and of JAK/STAT pathways, tofacitinib, in PsA. Moreover, we report data on the other JAK inhibitor, baricitinib, and the A(3) adenosine receptors agonist, CF101, emerging by studies conducted in psoriasis patients. Expert opinion: In Psoriatic Arthritis, apremilast appears promising for PsA and recent studies have shown a good efficacy and an acceptable safety profile. Data on tofacitinib in PsA are limited. Studies on the small molecules, baricitinib and CF101 are still incomplete and limited to trials conducted in Rheumatoid Arthritis and in psoriasis. Further studies on small molecules and on their underlining mechanisms are advocated in PsA.

Osteoporosis and psoriatic arthritis.

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.