Ultrasound assessment of lacrimal glands: a cross-sectional study in healthy subjects and a preliminary study in primary Sjögren's syndrome patients.

OBJECTIVES: This study aimed to: i) perform an ultrasonographic (US) evaluation of the lacrimal glands (LGs) in healthy subjects in order to define the sonographic elementary lesions which could be identified in the LGs and describe their frequencies in healthy subjects; ii) test the intra and inter-rater agreement between four rheumatologists; iii) preliminary assess whether the elementary lesions of the LGs let us differentiate healthy subjects from primary Sjögren's syndrome (pSS) patients. METHODS: A consensus meeting was held to define the sonographic lesions to be evaluated. Healthy subjects and pSS patients underwent lacrimal glands ultrasound (LGUS) examinations in two Italian Rheumatology Clinics. A web-based reliability exercise was performed on healthy subjects' images by four rheumatologists. Afterward, images of pSS patients were evaluated for the presence of the sonographic lesions previously defined and compared to the US findings in healthy subjects. RESULTS: Fifty-seven healthy subjects and 17 pSS patients were evaluated. The intra and inter-rater reliability score was good-excellent for almost all the agreed US features assessed (glandular parenchyma visibility, size, homogeneity, hypoechoic areas, hyperechoic spots, fibrous gland appearance, fatty deposition). Among the LGUS elementary lesions in pSS patients compared with healthy subjects, we detected a significantly difference in glandular inhomogeneity [13/33 (39.4%) vs. 9/63 (14.3%), p=0.01], and in fibrous gland appearance [3/33 (9.1%) vs. 0/63 (0%), p=0.04]. CONCLUSIONS: In this preliminary study, LGUS proved to have a good-excellent intra and inter-rater reliability. The glandular parenchyma inhomogeneity and the fibrous gland appearance could help differentiate pSS patients from healthy subjects.

Anti-interleukin-1 treatment in patients with rheumatoid arthritis and type 2 diabetes (TRACK): A multicentre, open-label, randomised controlled trial.

BACKGROUND: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). METHODS AND FINDINGS: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (ß: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (ß: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (ß: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (ß: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs. CONCLUSIONS: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. TRIAL REGISTRATION: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481.

The EPIPSOFIRE project: a preliminary report.

Psoriatic arthritis (PsA) is a musculoskeletal condition complicating psoriasis that can lead to joint deformity and disability; however, psoriatic patients may suffer from other kind of arthropathies that could be confused with PsA by nonrheumatologists. Our aim was to determine the prevalence of PsA and to determine the prevalence of other musculoskeletal conditions in a cohort of psoriatic patients. In this cohort, musculoskeletal discomfort was frequently reported, while inflammatory disorders were detected in <4% of subjects. The cohort lacked subjects with very long-standing psoriasis duration (>20 years) or severe cutaneous disease. Because musculoskeletal discomfort symptoms affected about 62% of patients, other disorders, particularly morphologic conditions, need careful evaluation in psoriasis subjects.

Not simply a matter of psoriatic arthritis: epidemiology of rheumatic diseases in psoriatic patients.

This study investigated the occurrence of rheumatic conditions (RCs) in a psoriasis (PSO)-dedicated dermatological clinic. PSO subjects with musculo-skeletal discomfort, and/or carrying signs (articular/systemic, even asymptomatic) of RCs; and/or suffering flares of previously established psoriatic arthritis (PsA) were referred to rheumatologist for evaluation. Laboratory tests/imaging were performed as needed. Categorization adhered to RCs classification endorsed by the Italian Society of Rheumatology. Of the 1,200 psoriatic subjects, 277 (23.1 %) were enrolled (146 females). The mean age was 55.7 years (range 21-81), PSO duration was 13.5 years (range 0-62). Thirty-seven patients (13.4 %) were asymptomatic. On an average, 92 (7.6 %) patients/year were evaluated, of whom 79.4 % näive to rheumatological consultations (NRC). Osteoarthritis (OA) and PsA (isolated or combined) showed the highest prevalence, with 156 (56.3 %) and 110 cases (39.7 %), respectively. Among NRC subjects, the mean PsA annual incidence was 29.5 % (standard error of the mean ±5.4 %). Other RCs, isolated or associated with PsA/OA, were diagnosed in 31 cases (11.2 %). Thirty-two subjects (11.5 %) had arthralgias, 20 of whom due to congenital/mechanical disorders, the remaining were unclassifiable. In conclusion, the largest part (88.5 %) of PSO subjects referred to rheumatologist showed some RCs. On annual basis, 29.5 % of näive enrolled patients were diagnosed as PsA.

Step-down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis.

OBJECTIVE: To evaluate the feasibility and outcome of the step-down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA). METHODS: Fifty-seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single-agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated. RESULTS: When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (+/- SEM) of survival on treatment was 0.273 +/- 0.09 for CSA and 0.852 +/- 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups. CONCLUSION: Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step-up approach) may be more appropriate in early RA.