Background Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. Methods 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. Findings Of the 53 SARS-CoV-2 pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO 2 /FiO 2 :146(IQR:120–212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO 2 /FiO 2 : 112(IQR:100–141.5)]. Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5–8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. Interpretation IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

Background Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Ab neg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Ab neg RA and test their predictive value of therapeutic response. Methods Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Ab neg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68 + , CD3 + , CD20 + , CD21 + , CD117 + , and CD138 + cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Ab neg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations. Results At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68 + and sublining CD21 + , CD20 + , and CD3 + cells than Ab neg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117 + cells ( p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Ab neg RA patients. Conversely, Ab neg RA patients showed higher IHC score of CD138 + cells, irrespective to the therapeutic scheme ( p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3 + cells compared to PsA patients not reaching this outcome ( p = 0.02); conversely, naive Ab neg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68 + cells compared to Ab neg RA patients not reaching this outcome ( p < 0.001). Conclusions CD117 + and CD138 + cell...

Objective This study applied a synovitis score obtained during routine care from ultrasound (US)–guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment‐naive rheumatoid arthritis (RA) patients. Methods The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal‐induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US‐guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat‐to‐target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. Results The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment‐naive RA patients. Moreover, at baseline, treatment‐naive RA patients achieving 6‐month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment‐naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28‐based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment‐naive RA patients yielded an up to 81.7% probability of achieving 6‐month remission according to the DAS28. Conclusion The KSS is a reliable tool for synovitis assessment on US‐guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response–predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.

Importance: Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective: to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design: Observational clinical cohort study. Setting: Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants: Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd − April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measures: We describe the clinical outcomes of 53 patients with SARS−CoV−2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results: Of the 53 SARS−CoV−2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120−212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100−141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re−admitted to the ward within 5-8 days. At 19 days median follow−up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance: IL6−R inhibition appears to be a potential treatment strategy for severe SARS−CoV−2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety.