Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire.

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

Very low dose glucocorticoid therapy in rheumatoid arthritis: Impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal.

OBJECTIVES: We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. RESULTS: We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off, and 23% had permanently discontinued very low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very low-dose GCs cessation (OR 1.1, 95% CI 1.03-1.14 for any 1-year decrease; p= 0.001). A significant association existed between ongoing utilization of very low-dose GCs and persistent moderate disease activity. Use of very low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). CONCLUSION: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.

Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data. Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group). Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis. Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets.

Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: An analysis on a nation-wide database.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis. METHODS: We conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk. RESULTS: We found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18-1.49 and 2.43, 95 % CI 2.17-2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively). CONCLUSION: Some glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

OBJECTIVE: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. METHODS: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. RESULTS: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. CONCLUSION: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Antiphospholipid antibody carriers and patients with quiescent antiphospholipid syndrome show persistent subclinical complement activation.

OBJECTIVES: Complement activation has been advocated as one mechanism by which antiphospholipid antibodies (aPLs) can induce thrombosis. In patients with catastrophic aPL syndrome or re-thrombosis, enhanced complement activation was shown, even in quiescent phase of the disease. We aimed to assess complement activation and to investigate its association to clinical variables in aPL positive patients with a favorable disease course. METHODS: Subjects with at least two consecutive positive aPL antibody results obtained ≥12 weeks apart were enrolled. They were subjects without history of thrombosis or pregnancy morbidity (aPL carriers), patients with pregnancy morbidity alone (OAPS), and/or with arterial, venous, or small-vessel thrombosis (TAPS); all patients should have been free of symptoms for ≥2 years. Patients affected with systemic autoimmune diseases were excluded. Healthy age and sex-matched subjects were included as controls. Plasma C5a and C5b-9 levels were assessed by commercially available ELISA assays. Non-parametric Mann-Whitney test and Spearman's correlation were applied. RESULTS: Thirty-seven OAPS, 38 TAPS, 42 aPL carriers, and 30 healthy subjects were enrolled. Median C5a and C5b-9 levels were significantly higher in quiescent aPL positive patients (OAPS, TAPS, aPL carriers) compared with controls: C5a ng/ml 10.61 (IQR 6.87-15.46) vs 4.06 (2.66-7.35), p< 0.001; C5b-9 ng/ml 283.95 (175.8-439.40) vs 165.90 (124.23-236.8), p< 0.001. Similar C5a and C5b-9 levels were observed in OAPS and TAPS patients and aPL carriers. A positive correlation between C5b-9 median levels and the number of aPL positive tests was found (p= 0.002). CONCLUSIONS: The persistence of aPL antibodies is associated to a persistent subclinical activation of the complement cascade.

Novel insights into the management of rheumatoid arthritis: one year in review 2023.

New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology.

OBJECTIVE: To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. METHODS: Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. RESULTS: Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). CONCLUSION: The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

New onset and flare of rheumatic diseases following COVID-19 vaccination are mild and respond well to treatment: 9-month follow-up data from a single centre cohort.

OBJECTIVES: Anti-COVID-19 vaccines have proved to be effective and well tolerated. Great attention is now being paid to the characterisation of possible adverse events associated to their administration. We report a case series of suspected rheumatic diseases (RDs) following anti-COVID-19 vaccination. METHODS: We included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padova University Hospital between May and September 2021 presenting with a RD within 30 days after an anti-COVID-19 vaccine dose. Our selection was in accordance with the World Health Organisation guidelines for adverse event following immunisation (AEFI) surveillance. Patients were regularly re-evaluated by telemedicine or face-to-face visit. RESULTS: We identified 30 cases of RD following vaccination: 24 (80.0%) new onsets and 6 (20.0%) flares. Most of patients (76.6%) received the BNT162b2 vaccine. The mean time to RD onset/flare was 12±9 days. The most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (33.3%) and adult-onset Still's disease (13.3%). At the last FU visit (9.6±2.2 months), 83.3% of patients showed complete response to first- or second-line therapy, 13.3% a partial response and one patient (3.3%) was still experiencing an active disease. CONCLUSIONS: Considering the amount of vaccine doses administered during the evaluation period we overall detected a limited number of cases. We noted a clear prevalence of autoinflammatory conditions and seronegative manifestations. The great majority of patients had mild features and showed a good response to therapy.

Early characterization of difficult-to-treat rheumatoid arthritis by suboptimal initial management: a multicentre cohort study.

OBJECTIVES: To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). METHODS: In this retrospective multicentre cohort study conducted from 09/2021-03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000-2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. RESULTS: We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P < 0.001). In multiple regression, treatment delay beyond 3 months (OR 0.3; 95% CI 0.1, 0.9) and non-discontinuation of glucocorticoids after 6 months (OR 4.6; 95% CI 2.2, 9.5) were significantly associated with D2T-RA. Treatment delay was significantly associated with PIRRA only, while non-discontinuation of glucocorticoids was significantly associated with PIRRA and NIRRA. Results were replicated in sensitivity analyses. CONCLUSION: Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Systemic lupus erythematosus incidence and prevalence in a large population-based study in northeastern Italy.

OBJECTIVES: We aimed at estimating the incidence and prevalence of SLE in northeastern Italy over the period 2012-20. METHODS: A retrospective population-based study was conducted in Veneto Region (4.9 million people) using the population registry, an administrative health database where all residents are recorded. Between 2012 and 2020, SLE prevalence was defined by a healthcare co-payment exemption for SLE (national registry code 028) or any hospital diagnosis of SLE (International Classification of Disease , Ninth Revision, Clinical Modification 710.0), whichever came first. Incident SLE was defined from 2013 to 2020 to exclude prevalent cases. Standardized incidence and prevalence rates were reported by age and sex. RESULTS: During the study period, we identified 4283 SLE patients (85% female), with 1092 incident cases. Across the study period, SLE standardized point prevalence increased from 63.5 (95% CI 61.2, 65.8) to 70.6 (95% CI 68.3, 73.0) per 100 000 residents, corresponding to an annual increment of 1.14% (P < 0.0001). The highest prevalence was observed in females aged 60-69 years. SLE incidence corresponded to 2.8 per 100 000 person-years (95% CI 2.6, 2.9), with an annual decline of 7.3% (P < 0.0001). Incidence was 5-fold higher in females (female-to-male incidence rate ratio: 5.00, 95% CI 4.25, 5.87; P < 0.0001), with a peak among women aged 30-39 years. At diagnosis, women were significantly younger (45 years, IQR 33-58) than men (52 years, IQR 38-64). CONCLUSIONS: Over the last decade, SLE prevalence has increased, while incidence has stably declined. In view of the introduction of new high-cost drugs, a clear definition of the epidemiology of SLE is crucial for all healthcare stakeholders.

Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud's phenomenon and digital ulcers. The suggested dose is 0.5-2 ng/kg/min for 6-8 h, and the maximum dose is decided upon the patient's tolerance. Objectives: This study aims to analyze ILO infusion tolerance and possible predictive factors in patients with SSc. Design: This is a retrospective observational study. Method: We evaluated 113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the incidence of adverse events (AEs), and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical and employed generalized linear models to assess possible predictors of maximum tolerated ILO infusion rate and AEs and logistic regression to assess predictors of AEs. Results: The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (ß = -0.21, p = 0.02) after correction for relevant confounding factors. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence interval (CI) = 2.359-82.845]. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the patients at least once. Conclusion: This study showed that higher BMI was statistically associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO regimens still need to be tailored to the patient. Plain Language Summary: Introduction: Systemic sclerosis is a rare a rheumatic disease characterized by skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs involvement. Iloprost, which is administered as intravenous infusion, is one of the main treatments for this disease, and it is effective in reducing vasospasm and the frequency of DUs. Even if there is a suggested dose range, the exact dose must be tailored on each patient, because the tolerance to the drug is variable. Tolerance is limited by dose-dependent unwanted effects, as headache, low blood pressure, dizziness, and sickness. This study aimed to identify possible predictors of such tolerance.Materials and Methods: We collected data from our patients with systemic sclerosis beginning the treatment with iloprost between January 2004 and November 2021 at our hospital facility in Verona, Italy, and analyzed different factors that could be associated with a better tolerance, as age, sex, disease duration, smoking habit, body mass index (a measure of body fatness), blood pressure, concomitant medications, and different patterns of the disease.Results: We found that a higher body mass index was associated with lower iloprost tolerance and higher adverse events rate in patients with systemic sclerosis, while we did not find a correlation with other factors. We believe overweight and obese patients (who have a higher body mass index) have a defect in the vasodilatation mechanism and can therefore be more susceptible to the effect of this medication.Conclusions: While preliminary, our results could provide a good starting point to develop a predictive tool to limit adverse events during this therapy.

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort.

OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Subclinical Myocardial Fibrosis in Systemic Lupus Erythematosus as Assessed by Pulse-Cancellation Echocardiography: A Pilot Study.

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43-16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature.

INTRODUCTION: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. MATERIALS AND METHODS: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. RESULTS: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. CONCLUSION: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Novel insights into the management of rheumatoid arthritis: one year in review 2022.

New evidence for the treatment of rheumatoid arthritis (RA) has emerged during the last year. Specifically, updated guidelines on pharmacological and non-pharmacological management of RA have emphasised the necessity of global patient's care, and have shifted the role of some older drugs, such as glucocorticoids and methotrexate. In addition, the long-term safety of Janus kinase inhibitors was investigated and reinforced. With respect to the coronavirus-19 pandemic, reassuring data on the efficacy and safety of vaccinations in the RA population were acquired, as well as on the potential role of telemedicine in RA management. Machine learning prediction models and biomarkers development have emerged as promising innovations in the area of precision/personalised medicine, appearing to encourage future expansion.In this narrative review, the authors aim to give their specific point of view on the most relevant and potentially impacting novelties published during 2021 and early 2022 in the context of RA management.