Search

Strategies aimed at expediting immunisation campaigns against COVID-19 include providing single vaccine doses to individuals with previous exposure to SARS-CoV-2 and delaying second doses. While such approaches are effective at the population level, immunogenicity yielded by one dose of vaccines in immunocompromised patients may be alarmingly low.1 2 Biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) interfere with the immune system at multiple levels and may variably reduce response to viral vaccines.3 Limited data on small numbers of rheumatic patients with variable diagnoses and treatments hamper definitive conclusions on the possible impact of immune-mediated inflammatory diseases, immunomodulatory drugs or both on the efficacy of the new generation of mRNA vaccines.4 5 Here we present interim data analysis on the immunogenicity of the BNT162b2 COVID-19 vaccine in 140 patients with chronic inflammatory arthritis all treated with b/tsDMARDs at the Division of Rheumatology of the IRCCS Policlinico San Matteo University Hospital of Pavia, receiving the first dose of vaccine between 24 and 31 March 2021. Patients were advised to discontinue both the b/tsDMARD and concomitant methotrexate around vaccination. In particular, the following suggestions were made: (1) for all the bDMARDs and methotrexate, withholding of therapy in the 7 days before and after vaccination; and (2) for tsDMARDs, withholding of therapy from the day before until day 7 after vaccination. For glucocorticoids and conventional synthetic DMARDs other than methotrexate, no modifications were advised. Blood samples were obtained immediately before vaccination and at day 21 after the first dose. Serum samples were tested using chemiluminescent immunoassay (LIAISON SARS-CoV-2 S1/S2 IgG; DiaSorin) for the quantitative characterisation of SARS-CoV-2 anti-S1 and anti-S2 IgG antibodies, with values >15 AU/mL indicating a positive result. Demographic and clinical variables were retrieved from the last available rheumatological assessment (median (IQR) 14 (5–19) days before vaccination) …

The prevalence of osteoporosis is about three times greater in people living with HIV than in the general population. Bisphosphonates are the only class of antiresorptive drugs which have proved to be safe and effective in HIV patients. However, bisphosphonates are not recommended in women of childbearing age due to an increased rate of associated neonatal complications. To the best of our knowledge no reports on the use of denosumab in HIV-infected individuals have been published so far. We describe a 38 year-old woman with HIV, osteoporosis and vertebral fractures treated with denosumab, a monoclonal antibody targeting RANKL. After four years of treatment, bone mineral density improved, no new fractures occurred, and neither HIV reactivation nor opportunistic infections were observed. We show that denosumab could be a safe and effective approach for osteoporosis in patients with HIV and could be considered in women of childbearing age.

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research. ispartof: LANCET vol:397 issue:10271 pages:305-317 ispartof: location:England status: published

Objectives Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). Methods A case–control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Results The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. Conclusions Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc).Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests.Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p0.03 and p0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p0.05) and on morning stiffness at 6 and 12 months (p0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p0.05). No changes in lung or gastrointestinal involvement were found.ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

ObjectivesTo investigate the association of anti-citrullinated protein antibodies (ACPA) with changes in systemic bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) after two years of treat-to-target.MethodsBMD was measured at the lumbar spine (LS) and femoral neck (FN) in 100 patients with recent onset RA at baseline and after 24 months of treatment aimed at low disease activity (LDA) according to the 28-joints disease activity score (DAS28 ResultsAfter 24 months, the majority of the patients were at least in LDA (78%), with slightly more ACPA-positive subjects achieving the target. The BMD had significantly decreased at both the LS (mean [SD] percent loss -1.8 [6.2], p=0.03) and the FN (-2.4 [7.3], p=0.03) in ACPA-positive but not in ACPA-negative patients. Consequently, the proportion of patients with reduced BMD (Z score ≤-1) after 24 months was significantly higher among ACPA-positive patients at both the spine (39.5% vs 19.3%, p=0.05) and the hip (37.2% vs 12.2%, p=0.007). The association between ACPA and BMD loss was independent of other variables including age, gender, disease activity, cumulative dose of glucocorticoids and duration of therapy with bisphosphonates at the LS but not the FN.ConclusionsACPA are associated with ongoing BMD loss at the spine despite suppression of inflammation and adoption of prophylactic measures. ACPA-positive RA patients should be therefore strictly monitored for the development of osteoporosis.

Background: Patients with established rheumatoid arthritis (RA) frequently miss Boolean remission solely because of the patient global assessment of disease activity (PGA) exceeding the cut-off of 1. Here, we investigated the frequency and the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs according to a treat-to-target strategy, depending on the autoantibody status. Methods: Data were retrieved from 535 early RA patients (1 was responsible for the majority of near-misses (56.2% and 57.6% at 6 and 12 months, respectively), and PGA >1 accounted for approximatively 35% of the cases. None of the variables of disease activity neither patient reported outcomes at baseline could discriminate SJC28 from PGA near-misses. Rather, autoantibody-positivity independently predicted the risk of missing remission because of SJC28 >1 with an adjusted OR [95% CI] of 3.62 [1.89-6.93] at 6 months and 2.36 [1.25-4.47] at 12 months, whilst autoantibody-negativity was an independent predictor of PGA near-miss (adjusted OR [95% CI] 2.71 [1.31-5.64] at 6 months and 6.50 [2.47-17.12] at 12 months). Conclusions: In patients with early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst the PGA more frequently impairs the achievement of remission in autoantibody-negative patients. These findings indicate that efforts to target full-remission in early RA may require different treatment strategies according to the autoantibody profile.

The purpose of this review is to discuss the most recent evidence on the treatment innovations and future prospective in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). In AAV, a growing body of research is available on novel treatment options for remission induction and to clarify some uncertainties concerning the optimal use of available drugs. Efforts are being made to reduce the toxicity associated with high-dose, prolonged glucocorticoids (GC) regimens. Despite major advances in the prognosis of AAV, relapses are still common and the intensity and duration of remission treatment constitute a great challenge in the management of these chronic conditions. A paradigm shift in practice in the management of AAV is being supported by recent evidence suggesting the comparable efficacy and improved safety profile of schemes with a reduced dose of GC for the induction and maintenance of remission in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Moreover, recent appraisal of pathogenetic mechanisms, including complement activation pathways, has introduced the revolutionary concept of an alternative to GC, such as avacopan. Plasma exchange failed to prevent end-stage renal disease and mortality in patients with severe renal involvement or pulmonary haemorrhage according to a large multicentre randomised trial. Intensified immunosuppressive strategies for patients with life-threatening manifestations, including the combination of rituximab (RTX) with cyclophosphamide (CYC) have revealed promising preliminary data. New evidence for the use of alternative immunosuppressive agents (e.g. mycophenolate mofetil or abatacept) for the induction of remission in patients with non-severe disease is emerging. Several studies have been recently published, or are ongoing, to assess the optimal strategy and duration of maintenance of remission with the available treatment options (GC, azathioprine, and RTX). Preliminary evidence supports the superiority of a more prolonged course of maintenance treatment. The management of refractory or relapsing eosinophilic granulomatosis with polyangiitis (EGPA) has been improved by the recent demonstration of efficacy and safety of an interleukin-5 inhibitor, mepolizumab. Ongoing randomised studies will clarify the role of RTX in patients with severe manifestations of EGPA.

Luciana Scalone,1 Piercarlo Sarzi-Puttini,2 Luigi Sinigaglia,3 Carlomaurizio Montecucco,4 Roberto Giacomelli,5 Giovanni Lapadula,6 Ignazio Olivieri,7,8,† Angela Maria Giardino,9 Paolo Angelo Cortesi,1 Lorenzo Giovanni Mantovani,1 Monica Mecchia9On behalf of the CARA Study Group1Centre of Research on Public Health, University of Milano-Bicocca, and CHARTA Foundation, Milan, Italy; 2Rheumatology Unit, L. Sacco University Hospital, 3Rheumatology Unit, G. Pini Hospital, Milan, Italy; 4University of Pavia School of Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; 5Rheumatology Unit School of Medicine, University of L’Aquila, L’Aquila, Italy; 6Rheumatology Unit, University of Bari, Bari, Italy; 7Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Potenza, Italy; 8Madonna delle Grazie Hospital of Matera, Matera, Italy; 9MSD Italy, Rome, Italy†Dr Ignazio Olivieri passed away on July 28, 2017Objective: To estimate preferences in relevant treatment characteristics evaluated by different groups involved in the management of patients with rheumatic diseases.Subjects and methods: We surveyed patients with rheumatic diseases, and rheumatologists, nurses, and pharmacists with experience in treatment with/provision of biologic drugs for these patients. Through a discrete choice experiment, participants evaluated 16 possible scenarios in which pairs of similarly efficacious treatments were described with six characteristics: 1) frequency of administration; 2) mode and place of administration; 3) manner, helpfulness, efficiency, and courtesy of health personnel; 4) frequency of reactions at the site of drug administration; 5) severity of generalized undesired/allergic reactions; and 6) additional cost. The direction and strength of preferences toward each characteristic level and the relative importance of each characteristic were estimated through a random-effects conditional logistic regression model.Results: In total, 513 patients, 110 rheumatologists, 51 nurses, and 46 pharmacists from 30 centers in Italy participated. Characteristics 3, 4, and 6 were the most important for every subgroup; 1 was least important for patients and rheumatologists, 2 was least important for pharmacists, and 2 and 5 were least important for nurses. For characteristic 2, pharmacists preferred subcutaneous self-injection with a syringe; nurses preferred assisted infusion at an infusion center close to the patient’s home; patients and rheumatologists preferred subcutaneous self-injection with a pen.Conclusion: The different preferences for some characteristics shown by the different groups can play an important role, together with purely clinical aspects, in the choice and consequent benefit of treatments, contributing also to a more satisfactory use of resources.Keywords: preferences, biologic drugs, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, decision making

Objectives To assess available evidence from randomized controlled trials (RCTs) and observational studies including a control group regarding the role of trimethoprim/sulfametoxazole (TMP/SMX) in reducing the relapse rate in patients with granulomatosis with polyangiitis (GPA) and the risk of infections in patients with ANCA-associated vasculitis (AAV). Methods MEDLINE, EMBASE, The Cochrane Library databases, Scopus, Web of Science and ClinicalTrials.gov were searched from inception until 15 January 2020 to identify controlled studies assessing the role of TMP/SMX in reducing the rate of relapse in patients with GPA (primary outcome) and the number and/or severity of infections in patients with AAV (secondary outcome). Two reviewers independently selected eligible studies and extracted data. Cumulative risk ratios (RRs) with 95% CI were calculated using a random effect meta-analysis. Results Eight studies were selected out of 2907 records. Seven studies (520 patients) (of which two were RCTs) assessed the role of TMP/SMX in the relapse rate in patients with GPA. TMP/SMX was not associated with a reduced risk of relapse (RR = 1.15, 95% CI: 0.51, 2.55; I2 = 78.5%; P Conclusion TMP/SMX was not associated with a reduced risk of relapse in patients with GPA. TMP/SMX might be useful in the reduction of infectious complications. Prospero database registration code CRD42019118983.

Eosinophilic granulomatosis with polyangiitis (EGPA), traditionally known as Churg–Strauss syndrome, is a form of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a group of...

Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Objectives Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Clinical Trial registry name and registration number: Zeus study, NCT02403115

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA). Methods: Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared. Results: 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012). Conclusions: Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies., In this Perspective article, members of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases discuss clinical and organizational challenges in this community caused by the COVID-19 pandemic and what lessons might be learned for the future.

BackgroundPrevalence 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.MethodsThe 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.ResultsThe 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.ConclusionsDuring the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection.Trial registrationRetrospectively registered. Not applicable.

Background and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

The effects of cytokine inhibition in the different phases of the severe coronavirus disease 2019 (COVID-19) are currently at the center of intense debate, and preliminary results from observational studies and case reports offer conflicting results thus far. The identification of the correct timing of administration of anti-cytokine therapies and other immunosuppressants in COVID-19 should take into account the intricate relationship between the viral burden, the hyperactivation of the innate immune system and the adaptive immune dysfunction. The main challenge for effective administration of anti-cytokine therapy in COVID-19 will be therefore to better define a precise “window of therapeutic opportunity.” Only considering a more specific set of criteria able to integrate information on direct viral damage, the cytokine burden, and the patient’s immune vulnerability, it will be possible to decide, carefully balancing both benefits and risks, the appropriateness of using immunosuppressive drugs even in patients affected primarily by an infectious disease.

Challenges in the provision of care and patients’ reluctance to access healthcare services and adhere to drug prescriptions in course of COVID-19 pandemic undermine the fundamental principles of early diagnosis and treat to target, which have revolutionised the natural history of many chronic inflammatory diseases starting from rheumatoid arthritis (RA).1 Although most rheumatologists have the impression that the intervals between symptom onset and first consultation have increased,2 no data currently indicate whether and to what extent the picture of early RA has changed during COVID-19. Here, we analysed data from the Pavia Early Arthritis Clinic (EAC) inception cohort. Referral criteria have been described previously, and include the presence of signs and symptoms of suspected inflammatory arthritis for

Background:There is renewed interest in the role of autoantibodies to predict outcomes in systemic sclerosis (SSc). Among the newly identified subsets, patients with limited cutaneous form (lcSSc) but anti-topoisomerase I antibodies (Scl70) positivity draw particular attention, and namely, assessing the risk of developing interstitial lung disease (ILD) —the main cause of death in SSc—to improve the management of Scl70-lcSSc patients.Objectives:We aimed to characterize patients with Scl70-lcSSc in the large multicenter European Scleroderma Trial and Research (EUSTAR) cohort.Methods:The EUSTAR database was locked in July 2019. We included all patients fulfilling 1980 ACR and/or 2013 ACR/EULAR criteria for SSc, with disease duration at database entry ≤3 yrs and known and stable skin form during the first 3 yrs. Patients with lcSSc were compared: Scl70-lcSSc (target group) vs. ACA-lcSSc and ANA-lcSSc (Step 1); and Scl70-lcSSc vs. Scl70-dcSSc (Step 2). In the ANA subgroup we included ANA+ patients with negative SSc-specific antibodies (Scl70, ACA, RNA polymerase III). In each step, we performed 5 generalized mixed models (GMM) for the risk of the new onset of ILD (defined by imaging), primary myocardial involvement (PMI), pulmonary hypertension (PH), “any severe” (ILD+PMI+PH+scleroderma renal crisis) and all-cause-mortality. An additional GMM assessed the risk of forced vital capacity (FVC) decline ≥10% vs. FVC value at ILD onset. Each GMM was adjusted for age, sex and confounders.Results:Overall, 1285 SSc patients were included: 1068 (83%) females, 860 (67%) lcSSc and 425 (33%) dcSSc. Among patients with lcSSc, 537 (62%) had ACA+, 194 (23%) Scl70+ and 129 (15%) ANA+; 425 patients had dcSSc and Scl70+. Median follow-up was similar in all 4 groups: 7.2 to 8.1 yrs.Step 1: At baseline, Scl70-lcSSc patients had significantly shorter time from Raynaud’s phenomenon (RP) to SSc onset, higher mRSS (5.8±4.8 vs. 4.3±4, p=0.001), and higher rate of articular and muscular involvement vs. ACA-lcSSc patients (Figure 1). No differences were found between Scl70-lcSSc and ANA-lcSSc comparing the aforementioned variables. ILD was more frequent in Scl70-lcSSc (46%) than in ACA-lcSSc (10%) and ANA-lcSSc (25%), as well as restrictive lung disease. GMM showed that Scl70-lcSSc carries a higher risk of ILD than both ACA-lcSSc (HR 4.55, 95%CI 3.23-6.67) and ANA-lcSSc (HR 2.17, 95%CI 1.39-3.45), with a rate of FVC decline ≥10% over time similar to the other limited forms. In Scl70-lcSSc patients the risk of “any severe” organ involvement was similar to ANA-lcSSc and higher than ACA-lcSSc (HR 1.89, 95%CI 1.40-2.50). In particular, Scl70-lcSSc shows a risk of PMI similar to ANA-lcSSc and lower than ACA-lcSSc; no differences regarding PH risk. The mortality risk in patients with Scl70-lcSSc was similar to the other limited forms’.Step 2: At baseline, time from RP to SSc onset was longer in patients with Scl70-lcSSc, with less frequent joint synovitis and tendon friction rubs vs. patients with Scl70-dcSSc. Conversely, the frequency of muscular, cardiac and pulmonary involvement was similar. The risk of ILD in Scl70-lcSSc patients was similar to Scl70-dcSSc, with a lower risk of FVC decline ≥10% over time. The risk of “any severe” involvement (HR 0.66, 95%CI 0.49-0.83), PMI and PH was lower and the mortality risk tended to be lower (HR 0.57, 95%CI 0.33-1.01, p=0.053) vs. Scl70-dcSSc.Conclusion:In our large multicenter EUSTAR cohort one quarter of lcSSc patients were Scl70+. We show a ranking for major organ involvement within lcSSc: Scl70 the most severe, ANA+ intermediate and ACA the milder form. Scl70-dcSSc patients present the most severe phenotype, and Scl70 positivity, more than the cutaneous subset, is strongly predictive of ILD, whereas other variables may influence progression. These results may provide new insight to improve the management of Scl70-lcSSc patients.Disclosure of Interests:Elisabetta Zanatta: None declared, Dörte Huscher: None declared, Paolo Airò: None declared, Alexandra Balbir-Gurman: None declared, Elise Siegert: None declared, Augusta Ortolan: None declared, Marco Matucci-Cerinic: None declared, Franco Cozzi: None declared, Gabriela Riemekasten: None declared, Anna-Maria Hoffmann-Vold: None declared, Oliver Distler Speakers bureau: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe, Armando Gabrielli: None declared, Stefan Heitmann: None declared, Nicolas Hunzelmann: None declared, Carlomaurizio Montecucco: None declared, Jadranka Morovic-Vergles: None declared, Camillo Ribi: None declared, Andrea Doria: None declared, Yannick Allanore: None declared

We appreciate the correspondence from Lecler et al 1 in response to our paper highlighting the impact of the COVID-19 epidemic on the delayed diagnosis of giant cell arteritis (GCA) leading to an increased rate of bilateral blindness.2 The colleagues described their experience with a similar fast-track clinic for the early diagnosis of GCA, reporting an increased incidence of GCA during the lockdown period without an increase in the severity or complications of the disease, nor an increase in referral delay. Interestingly, Lecler et al specified that their centre was not a referral centre for COVID-19 and that …

Objective To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. Methods Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab. Results The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. Conclusion Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region.

Background & Aims Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity. Methods In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 hours since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (

Background: Color Duplex sonography (CDS) of temporal arteries and large vessels (LV) is a recently validated diagnostic methodology for Giant Cell Arteritis (GCA). CDS combined with a fast-track approach (FTA) has improved the early diagnosis of the disease.Objectives: To assess FTA effects on the prevention of permanent visual loss (PVL), relapse and late complications of GCA compared to conventional practice. To assess the impact of COVID-19 pandemic on outcomes of GCA patients assessed with FTA.Methods: GCA patients diagnosed up to June 2020 at the Rheumatology Department, University of Pavia, were included. FTA was implemented since October 2016. FTA consists in the referral within 1 working day of a suspected GCA case to an expert rheumatologist who performs clinical evaluation and CDS.Results: One hundred sixty patients were recruited [female 120 (75%), mean age 72.4 ± 8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. FTA patients were older (75.1 ± 7.6 vs. 70.6 ± 8.2 years old; p < 0.001). Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p < 0.001). There was no difference between the two cohorts regarding major vessel district involvement (LV-GCA 17.5% vs. 22.7%; p = 0.4). PVL occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p = 0.03). The relative risk of blindness in the conventional group was 2.11 (95% C.I. 1.02–4.36; P = 0.04) as compared to FTA. Median symptom latency of patients experiencing PVL was higher in the conventional group (23 days IQR 12–96 vs. 7 days IQR 4–10, p = 0.02). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction (P = 0.2). No difference in late complications (stenosis/aneurysms) was detected.Conclusions: FTA including CDS evaluation contributed to a substantial reduction of PVL in GCA by shortening the time to diagnosis and treatment initiation. Relapse rate did not change upon FTA introduction, highlighting the need for better disease activity monitoring and treatment strategies optimization based on risk stratification that would predict the occurrence of relapse during glucocorticoid de-escalation.

Emerging reports have described the possible occurrence of arthritis in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1–3 Apart from crystal-induced arthritis,1 Yokogawa et al 2 and Alivernini et al 3 both described the onset of inflammatory arthritis with the characteristics of viral arthritis over the course of COVID-19. Here we would like to share a different case of monarthritis associated with psoriatic skin lesions presenting after resolution of SARS-CoV-2 infection. In April 2020, a patient in his 30s was admitted to our early arthritis outpatient clinic due to a 2-week history of painful limitation of the right elbow. The patient had no previous history of arthritis, back pain, enthesopathy, dactylitis, psoriasis (PsO) or other extra-articular symptoms of axial spondylarthritis, nor familiarity for rheumatic diseases and/or PsO. Forty days earlier, the patient had been suffering from arthromyalgia, fatigue, diarrhoea and anosmia, and had been diagnosed with COVID-19 based on reverse transcription (RT-PCR) detection of SARS-CoV-2 following nasopharingeal swab. Blood test analysis at …

We thank Dr Santos-Moreno et al 1 for their interest in our paper2 and for sharing their experience on telemedicine use in patients with rheumatoid arthritis (RA). We agree on the fact that a preliminary consultation is necessary to assess the willingness of the patients to be evaluated by telemedicine and, possibly, to explain them how the platform works. However, given the different setting in which we applied telemedicine—a connective tissue diseases (CTDs) outpatient clinic—our approach was slightly different. In fact, unlike inflammatory arthritis, in which disease flares are in most cases symptomatic and impacting on patients’ quality of life and functionality, CTDs like systemic lupus erythematosus (SLE) or systemic sclerosis may give rise to more insidious manifestations. In our …

We appreciate the comment from Dr Kobak1 to our previously published report on the clinical course and outcome of COVID-19 in a cohort of patients treated with biologic and targeted synthetic disease modifying antirheumatic drugs.2 The author described the case of a patient with familial Mediterranean fever treated with colchicine who experienced a mild course of …

We thank Lopez-Medina et al 1 for their comment on our paper and for sharing their experience with phone consultations.2 Telemedicine, in the past years, has been progressively implemented into medical practice. However, it has not been able to fully take root into routine medical care yet. The COVID-19 pandemic provided the opportunity to take a further step towards the integration between virtual and traditional medical assistance in many medical specialties including rheumatology. The restriction rules, taken over by numerous countries, together with the necessity of assuring a proper continuity of care, have forced us to adopt telemedicine tools in our routine involving chronic patients. To overcome legal matters of privacy and data protection, we have recently set up a …

We thank Dr Conticini et al 1 for their comment on our previously published paper describing the course of COVID-19 in a cohort of patients treated with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs).2 The authors commented on the low prevalence of subjects treated with bDMARDs in our cohort of patients affected by COVID-19; however, our paper actually described the course of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection in the cohort of patients attending our biologic clinic rather than the opposite. Nonetheless, assessing the prevalence of COVID-19 in patients treated with …

The outburst of the novel COVID-19 has caused unprecedented stress in the healthcare systems and global economy since its outbreak in December 2019. Effective treatment for severely ill patients still needs to be identified, and many countries are still pushed by daily increases in case numbers and deaths. Furthermore, before a vaccine is made available or drugs eventually capable of preventing the infection are identified, exit strategies in those countries that have managed to bend the transmission curve are inevitably governed by trial and error. The alarm remains high also because COVID-19 flare-ups are increasingly likely and a second wave in fall is seen as a real risk. The effects of hydroxychloroquine (HCQ) on COVID-19 remain at the centre of intense debate. In the laboratory setting, HCQ has initially shown promise by interfering with the attachment, internalisation and replication of SARS-CoV-2,1 2 the causative agent of COVID-19. Additional benefits have been inferred from the capacity of HCQ to modulate inflammatory responses via toll-like receptor inhibition,3 possibly hindering the cytokine storm leading to acute respiratory distress syndrome,4 and to exert anticoagulatory activities5 capable of ameliorating COVID-19-related systemic thrombosis.6 Very recently, however, results from in vitro assays have not been confirmed in vivo in non-human primates.7 In parallel, the early enthusiasm on the clinical efficacy of HCQ on COVID-19 coming on top of small case series and open-label non-randomised trials8 9 has rapidly deflated following the dissemination of the results from large randomised clinical trials (RCTs). Three studies ceased enrolment early because of lack of efficacy of HCQ versus control arm in preliminary analyses.10–12 Similarly, according to rigorous RCTs recently published on high-impact medical journals, the use of HCQ did not result in higher probability of negative conversion13 or neither improved clinical status …

The COVID-19 pandemic deeply affected northern-Italian regions.1 Lombardy and Emilia-Romagna had the highest cumulative incidence with 627.1 and 470.53 cases/100 000 inhabitants respectively on 16 April 2020 according to Italian ‘Istituto Superiore di Sanita’ (ISS). While a mild course has been reported in patients with chronic arthritis treated with targeted immunosuppressive agents,2 few and controversial data are available about COVID-19 in systemic lupus erythematosus (SLE).3 4 To this purpose, since 6 April 2020, given the mobility restriction imposed nationwide, we initiated a telemedicine project aimed at ensuring regular follow-up, starting from SLE patients.5 During the visit, we conducted a survey to investigate any COVID-19 related symptoms that occurred since 15 February 2020 and the results of available nasopharyngeal swabs. The survey was addressed to patients coming from Lombardy and Emilia-Romagna. We evaluated 165 patients (112 females, 84%, median age 52.5 years, range 25–81; median disease duration 13 years, range 1–53). Among them, 127 (77%) were on hydroxychloroquine …

We thank Capecchi et al 1 for their comment on our paper. The authors suggested that interleukin 6 (IL-6) represents the key cytokine responsible for the majority of pulmonary and cardiovascular complications of COVID-19. Similarly, we have received a comment from Gupta et al 2 who reported the management of rheumatological treatments during COVID-19 pandemic among practitioners in India, revealing that choices were apparently made according to the beliefs on the possible relationships between drug mechanism of action and effect on the viral infection. Both correspondence comments highlighted some striking similarities with changes seen in rheumatological conditions such as the systemic effects of chronic inflammation in rheumatoid arthritis, or laboratory findings resembling macrophage activation syndrome, and argued on the potential applications of rheumatological targeted therapies in this new context, especially …

We thank Dr Heldwein and Calado1 and Dr Joob and Wiwanitkit2 for their interest and comments on our paper.3 The authors raised the hypothesis that chronic use of hydroxychloroquine (HCQ) for the currently approved indications, such as systemic lupus erythematosus (SLE), could have an impact on the rate of COVID-19 and possibly on the clinical course of the infection. An in vitro antiviral effect of HCQ has been demonstrated on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence suggests that HCQ can interfere with the virus-receptor binding and proliferation, potentially suggesting a prophylactic and therapeutic role of the drug, together with the advantages of its immunomodulatory activity.4 5 Given the urgent need to identify an efficacious treatment to reduce mortality during the COVID-19 pandemic, HCQ has been included in a number of national protocols and guidelines to treat the infection, based on the results of preliminary clinical data. Nevertheless, the evidence supporting the use of HCQ in vivo is still based …

We thank Dr Guilpain et al 1 for their comment regarding the case of a patient with granulomatosis with polyangiitis who developed signs of systemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection shortly after having received treatment with rituximab. The comment raises a series of important points of discussion. The differential diagnosis between infectious complications or manifestations of the underlying rheumatological condition has always been a challenge when managing patients with systemic diseases such as antineutrophil cytoplasmic antibody-associated vasculitis (AAV) or connective tissue diseases (CTD). The clinical picture and laboratory and imaging findings in patients with AAV or CTD are often non-specific and need to be differentiated from changes caused by treatment or by infectious complication.2–4 SARS-CoV-2 has been associated with clinical manifestations and complications that can resemble some changes found in AAV or CTD. The cardiovascular risk, including the risk of deep venous thrombosis and pulmonary embolism, is increased also …

Different viral agents are associated with an increased risk of more severe disease course and respiratory complications in immunocompromised patients.1–3 The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) responsible for a severe acute respiratory syndrome (SARS) represents a source of concern for the management of patients with inflammatory rheumatic diseases. Lombardy is the region in Northern Italy with the highest incidence of COVID-19 cases, with more than 33 000 confirmed patients and 1250 requiring admission to the intensive care unit within 1 month. Since the first reports of COVID-19 cases in Italy, we have circulated a survey with a 2-week follow-up contact to patients with chronic arthritis treated with biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) followed up at our biological outpatient clinic in Pavia, Lombardy. The survey investigated the patients’ health conditions, the presence of contacts with subjects known to be affected by COVID-19 and management of …

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 has significantly challenged hospitals surge capacity and the perceived priorities for medical investigations performed to diagnose or monitor other diseases.1 2 Recent studies have reported increased mortality in out-of-hospital acute coronary syndromes, not fully explained by COVID-19 cases alone, and potentially related to the patients’ reluctance to seek medical care out of fear of the infection threat.3 4 Moreover, in the field of rheumatological disorders, general systemic symptoms, often evaluated by telephone triage, might be wrongly attributed to COVID-19, leading to delayed referral to specialist attention. The consequences of delayed diagnosis in rheumatology can be particularly evident in giant cell arteritis (GCA), leading to the most dreaded complication of the disease: irreversible visual loss. The aim of this analysis …

The aim of this study was to promote the construction of a real network and a shared diagnostic and therapeutic management model between hospitals and out-of-hospital healthcare services to capture as many patients with bone fragility as possible. Starting from the analysis of the clinical competences present in the province of Pavia, the bone specialists (BSs) organized some educational events involving both general practitioners (GPs) and hospital specialists. The Fracture Liaison Service (FLS) model, the revision of Note 79, the national plan for chronicity and the health reform of the Lombardy Regional Authority supported the structure of our model, in which the roles of clinicians are well defined and based on the complexity and severity of patients. In our method the GP has a central role as clinical manager, facilitating patient management and communication between the specialists and the BS. In January 2019, the Therapeutic Care Diagnostic Path (PDTA) shared between 2 bone specialists (BSs), 9 GPs, as reference treaters, and a multidisciplinary group of 25 specialists of the Province of Pavia was defined. The strategic directions of the two largest public hospitals in Pavia have supported the PDTA, which was validated by the quality departments of the hospitals themselves. Finally, sixty GPs belonging to the network have joined the PDTA. This model is the first example of integrated management between hospitals and out-of-hospital healthcare services for the primary and secondary prevention of fragility fractures (FF), where the GPs play a pivotal role as managers and supervisors to ensure proper care to chronic patients according to their levels of severity.

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

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 25th February to 20th 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 incidence was evaluated. Findings: 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 were observed. Interpretation: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. Funding: None. Declaration of Interests: Authors declare no competing interest. Ethics Approval Statement: The current analysis was approved by the Ethics Committees of the Gaetano Pini Institute and Policlinico San Matteo as part of a project to collect observational data from rheumatological patients followed at the two involved rheumatology units. All included patients have signed an informed consent to participate in the data collection. The possibility of including this survey within the abovementioned data collection project has been waived by the same ethics committee.

Objectives Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. Methods We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. Results ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P Conclusion PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.