Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Knee joint synovitis: study of correlations and diagnostic performances of ultrasonography compared with histopathology.

OBJECTIVES: Ultrasonography (US) is a fast, available and low-cost imaging tool used for detecting knee synovitis. Our aims were to assess the relationship between US and histology findings in appraising levels of inflammation and vascularity in the knee joint in subjects with inflammatory arthropathies; to determine whether differences exist in the appraisal between varying knee compartments and to compare US performances compared with gold standard histology for knee synovitis detection. METHODS: Subjects with actively inflamed knee joint having crystal arthropathies, rheumatoid arthritis, psoriatic arthritis or ostoearthritis were prospectively recruited from rheumatology clinics after giving their written consent between May and October 2015. Study was approved by the institutional ethics committee. The knee was divided into three compartments (medial, lateral, superior). Patients had a knee US followed by a knee arthroscopy with biopsies retrieval from each compartment. Biopsies were blindly scored for lining layer hyperplasia, inflammation, vascularity, CD68 and factor VIII staining. Correlation was determined using the Spearman's correlation test. RESULTS: 26 patients with active arthritis in a knee joint and recent onset of disease were prospectively included. Strong correlations were observed between US synovitis grade and histological inflammation score (r=0.63; P=0.002), US Doppler grade and histological score for vascularity (r=0.68; P<0.001); US measured synovial thickness and lining layer hyperplasia (r=0.61; P=0.002). Moderate correlation was found between US synovitis grade and CD68 score (r=0.49; P=0.02). CONCLUSION: US findings correlate with histological inflammation and vascularity scores in actively inflamed knee joints. US accurately describes knee synovitis.

Overview of osteo-articular involvement in systemic sclerosis: Specific risk factors, clinico-sonographic evaluation, and comparison with healthy women from the French OFELY cohort.

Osteoarticular involvement in systemic sclerosis (SSc) is frequent and varied. Data are scarce on the prevalence and risk factors of osteoporosis (OP). We aimed to assess clinical parameters, radiological parameters, US articular involvements, and the frequency of OP and evaluate SSc-specific risk factors. In a prospective cohort of 54 patients with SSc, data of OP risk factors, SSc organ involvements, tender and swollen joint counts, DAS28-CRP, hand US sonographies, X-ray hand views, and bone mineral density (BMD) were assessed. BMD values were compared to those from a healthy female population (OFELY cohort). Nineteen patients (40%) had OP. SSc was a risk factor of lower BMD in the patient group than in the control group. OP was associated with SSc-related risk factors and not with conventional OP risk factors. Nine patients had clinical synovitis (16%), and 23 (68%) patients had at least one US synovitis. No correlation was found with articular destruction, disease severity, autoantibody profile, or other organ impairment.

Ultrasound abnormalities in septic arthritis are associated with functional outcomes.

OBJECTIVES: To describe the ultrasound abnormalities seen in septic arthritis and to assess their associations with clinical, biological, and radiological outcomes. METHODS: We prospectively included 34 patients with septic arthritis of a native joint (knee, n=19; shoulder, n=6; hip, n=4; ankle, n=3; or wrist, n=2). Ultrasonography was performed to record synovial-membrane thickness and vascularity, joint effusion, and abnormalities of adjacent soft tissues, at baseline then 4days, 2weeks, and 3months later. Motion-range limitation of the affected joint was evaluated after 3months. Radiography was performed at inclusion and after 3months. RESULTS: Mean age was 63.7±17.6years. After 3months, 20 (58.8%) patients had motion-range limitation with worsening of the total radiological score (P<0.001). The proportion of patients with synovitis was very high initially (96.4% at baseline, 96.3% after 4days, and 100% after 2weeks) then diminished to 77.8% after 3months (P=0.051). Synovial-membrane thickness was significantly higher after 4days and 2weeks compared to baseline (median, +17.3% and +20%, respectively; P=0.015) and was significantly lower after 3months compared to the earlier time points (median, -31.5%, P=0.015). A positive Doppler signal was common at baseline (n=18, 64.3%) then significantly less so after 3months (n=7, 25.9%; P=0.04). An unchanged or higher Doppler grade after 2weeks compared to baseline was associated with motion-range limitation at last follow-up (P=0.033). CONCLUSION: We report the first study on ultrasound evidence of synovitis, joint effusion, and soft tissue alterations at baseline and over time in patients with septic arthritis. Persistent synovitis and joint effusion 3months after starting antibiotic therapy was not associated with treatment failure. However, Doppler signal changes over the first 2weeks were associated with the 3-month functional outcome.