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Background: Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis., Methods: The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated., Results: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed., Conclusions: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection., Trial Registration: Retrospectively registered. Not applicable.

Anti-Jo-1 is the most frequently detectable antibody in the antisynthetase syndrome (ASSD), an autoimmune disease characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). Recently, we organized an international collaborative group called American and European NEtwork of Antisynthetase Syndrome (AENEAS) for the study of this rare and fascinating disease. The group collected and published one of the largest series of ASSD patients ever described and with one of the longer follow-up ever reported. The number of participating centers is steadily increasing, as well as the available cohort. In the first paper, we showed that arthritis, myositis, and ILD may be frequently the only feature at disease onset, raising problems to reach a correct diagnosis of this syndrome. Nevertheless, we first observed that the ex novo appearance of further manifestations is common during the follow-up, strengthening the importance of a correct diagnosis. In our cohort, the 24 % of the 243 patients up to now collected had isolated arthritis as a presenting feature. These patients represent the most intriguing group in terms of differential diagnosis and clinical time course. Furthermore, data on this aspect are scanty, the reason that lead us to evaluate these aspects in our cohort of patients, reviewing also available literature. In fact, the most relevant aspect is that ASSD is rarely suspected in this setting of patients, in particular in case of poliarticular involvement, positive rheumatoid factor (RF), or anti-cyclic citrullinated peptide antibodies (ACPA) or evidence of joint erosions at plain radiographs. These findings were not rare in our cohort, and they have been also described in other series. Furthermore, manifestations such as Raynaud's phenomenon, mechanic's hands, and fever that may lead to the suspect of ASSD are observed only in a third of cases. If we consider the high rate of clinical picture progression in these patients, we feel that ASSD should be carefully considered in all patients presenting with isolated arthritis, even in those with erosive, RF, and ACPA-positive arthritis.

Objectives: Information on new drugs does not include their possible effects on pregnancy because pregnant women are excluded from clinical trials. Although not classified as teratogenic in animals, limited data is available on biological anti-rheumatic agents and their safety in human pregnancy. The aim of the study is to evaluate the safety of biological drugs in pregnant patients with chronic arthritis., Methods: Pregnancy outcome and maternal disease variations were prospectively followed in six Italian Rheumatology Centres. Patients exposed to biological agents during the periconceptional period or during pregnancy were included in the study. The occurrence of congenital malformations as well as the obstetric and neonatal outcomes were assessed., Results: Between 1999 and 2013 we identified 79 exposed pregnancies in 67 women affected by different rheumatic diseases with peripheral chronic arthritis. At the time of the start of pregnancy, 56 patients were taking etanercept, 13 adalimumab, 3 infliximab, 2 each certolizumab-pegol and rituximab, 1 each golimumab, anakinra and abatacept. Biological treatment was stopped after a mean of 41 days since documented pregnancy. Live births were reported in 66% of pregnancies. The rate of spontaneous pregnancy loss was 20%. Only one congenital malformation was reported., Conclusions: TNF-alpha inhibitors can be considered safe in the periconception period, representing a possible therapeutic choice also in young women affected by an aggressive form of chronic arthritis and hoping for a pregnancy. Reports of exposure during 2nd/3rd trimester are still limited and suggest caution. Experience with abatacept, tocilizumab, anakinra and rituximab in pregnancy is insufficient.

Objectives: To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists., Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc., Results: Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-α inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNF-α antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-α antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-α antagonists for arthritis associated with SSc., Conclusions: Most of the experts do not recommend the routine use of TNF-α antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given.

To describe the efficacy and safety of subcutaneous tocilizumab (SC-TCZ) in a cohort of juvenile idiopathic arthritis (JIA) patients with refractory uveitis. Retrospective observational monocentric study including patients with JIA-associated uveitis treated with SC-TCZ. Thirteen patients were enrolled. The rate of uveitis flare/year per each patient was 1.6 ± 2.0 on the last bDMARDs before SC-TCZ, while it decreased to 0.4 ± 0.7 on SC-TCZ. Nine out of thirteen patients (69%) required the introduction of SC-TCZ only for active uveitis at baseline. Among these patients, five (56%) achieved complete treatment response. No uveitis relapses were observed in patients (4/13, 31%) requiring the introduction of SC-TCZ for active arthritis during follow-up (30.48 ± 21.6 months). Overall, SC-TCZ was safe, and no side effects were observed during the treatment. SC-TCZ can be effective and safe in patients with JIA and uveitis recalcitrant to several bDMARDs. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils' role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

to summarize the evidence on the efficacy of minimally invasive interventional procedures such as radiofrequency ablation (RFA) and transcatheter arterial embolization (TAE) in patients with osteoarthritis or inflammatory arthritis. a literature search was conducted in PubMed and Web of Science databases. Both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) were included. The results were organized according to the treated anatomical site: knee, hip, foot and ankle, shoulder, hand and wrist, sacroiliac joints. Data about treatment efficacy were extracted. The main outcome was change in pain intensity using the 0–10 visual analog scale (VAS) from baseline to 1 month. Additional timepoints at 3, 6 and 12 months were assessed. Change in functional status was evaluated. Pooled estimates were calculated as the mean difference (MD) and 95 % confidence interval relative to baseline. The meta-analyses of RCTs and NRSI were conducted separately. of the 4599 retrieved articles, 164 were included in the review and, considering all the established timepoints, 111 (38 RCTs and 73 NRSI) were selected for the meta-analysis. Only one article described patients with inflammatory arthritis. In the meta-analysis of RCTs, one month after the procedure, MD in VAS was -3.98 (-4.41 to -3.55; k = 21) for knee RFA, and -3.18 (-3.96 to -2.39; k = 8) for sacroiliac joints RFA. In the meta-analysis of NRSI, MD in VAS was -4.12 (-4.63 to -3.61; k = 23) for knee RFA, -3.84 (-4.77 to -2.92; k = 7) for knee TAE, -4.34 (-4.96 to -3.71; k = 2) for hip RFA, -3.83 (-4.52 to -3.15; k = 3) for shoulder RFA and -4.93 (-5.58 to -4.28; k = 14) for sacroiliac joints RFA. Significant decrease in pain intensity was found also at 3, 6 and 12 months. Additionally, functional status improved at all the assessed timepoints. minimally invasive interventional procedures can improve pain and functional status of patients affected by OA or chronic sacroiliac pain of degenerative origin. Further research is warranted in the field of inflammatory rheumatic diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations' development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients' quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

Arthritides are a highly heterogeneous group of disorders that include two major clinical entities, localized joint disorders such as osteoarthritis (OA) and systemic autoimmune-driven diseases such as rheumatoid arthritis (RA). Arthritides are characterized by chronic debilitating musculoskeletal conditions and systemic chronic inflammation. Poor mental health is also one of the most common comorbidities of arthritides. Depressive symptoms which are most prevalent, negatively impact patient global assessment diminishing the probability of achieving the target of clinical remission. Here, we investigated new insights into mechanisms that link different joint disorders to poor mental health, and to this issue, we explored the action of the synovial fluid-derived extracellular vesicles (EVs) on neuronal function. Our data show that the exposure of neurons to different concentrations of EVs derived from both RA and OA synovial fluids (RA-EVs and OA-EVs) leads to increased excitatory synaptic transmission but acts on specific modifications on excitatory or inhibitory synapses, as evidenced by electrophysiological and confocal experiments carried out in hippocampal cultures. The treatment of neurons with EVs membrane is also responsible for generating similar effects to those found with intact EVs suggesting that changes in neuronal ability arise upon EVs membrane molecules′ interactions with neurons. In humans with arthritides, we found that nearly half of patients (37.5%) showed clinically significant psychiatric symptoms (CGIs score ≥ 3), and at least mild anxiety (HAM-A ≥ 7) or depression (MADRS and HAM-D ≥ 7); interestingly, these individuals revealed an increased concentration of synovial EVs. In conclusion, our data showing opposite changes at the excitatory and inhibitory levels in neurons treated with OA- and RA-EVs, lay the scientific basis for personalized medicine in OA and RA patients, and identify EVs as new potential actionable biomarkers in patients with OA/RA with poor mental health. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission.Methods. We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment. US indexes of grey scale (GS) and power Doppler (PD) synovitis were correlated with clinical evaluation, laboratory indexes and clinical outcome. Clinical remission was defined when DAS was <1.6 at two consecutive visits 3 months apart.Results. US examination was significantly more sensitive than clinical examination, both in active disease and in remission. In patients with an active disease, both clinical and US indexes correlated with CRP, whereas in remission only PD still remained significantly correlated. In clinical remission, 95% of the patients showed residual GS synovitis, and 41% of them showed a positive PD signal. Positive PD signal, even in a single joint, resulted the main predictor of relapse within 6 months, both in univariable and multivariable logistic regression analysis.Conclusions. In a cohort of early RA patients treated with conventional DMARDs, US-GS can detect residual disease activity more sensitively than clinical examination both in active disease and in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing inflammation even during remission and predicts short-term relapse. [ABSTRACT FROM PUBLISHER]

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1β or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19. [ABSTRACT FROM AUTHOR]