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Objectives: To evaluate the impact of obesity in patients with adult onset Still's disease (AOSD) and to assess their clinical characteristics and disease outcomes. Methods: The clinical features of AOSD patients with a body mass index (BMI) ≥ 30 were assessed among those included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. Results: Out of 139 AOSD patients, who had BMI registered in our database, 26 (18.7%) had a BMI ≥ 30. A lower rate of sore throat (P

Patients with chronic Inflammatory Arthritis (IA), such as Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) are more likely to experience psychosocial impairment. Gastrointestinal (GI) symptoms are also present, especially in Spondyloarthritis. No data are available on the relationship between gut and brain manifestations and their impact on daily activities in this setting; thus, this study aimed to assess these symptoms in an IA population and identify potential associations. IA patients and a control group were enrolled. The Patient-Reported Outcome Measurement Instrument System (PROMIS®) questionnaire was used to evaluate GI and psychosocial domains. The study included 389 subjects (238 controls and 151 with IA); demographic and clinical data were collected for each participant. IA patients reported both higher psychosocial and GI impairment compared with controls. The logistic regression model revealed a strong association between depression and belly pain (p = 0.035), diarrhea (p = 0.017), bloating (p = 0.018), and reflux (p = 0.01); anxiety was associated with belly pain (p = 0.004), diarrhea (p = 0.019), swallowing alterations (p = 0.004), flatulence (p < 0.001) and reflux (p = 0.008). Moreover, fatigue, sleep disorders, and pain interference were associated with almost all GI symptoms, whereas high physical function scores and satisfaction in social roles decreased the odds of most GI symptoms. IA patients had more significant impairment in both dimensions compared with controls. To address reported symptoms and improve the overall quality of life in rheumatologic patients, a new holistic approach is required.

We aimed to investigate the health-related quality of life (HRQoL) in Adult onset Still disease (AOSD) patients, a rare systemic auto-inflammatory disorder of unknown etiology usually affecting young adults. In this multicentre cross-sectional study, AOSD patients and age and gender matched healthy controls (HCs) were included. All patients had a low or absent clinical expressiveness, they were categorized as having a monocyclic pattern or a chronic disease course. The Health Assessment Questionnaire (HAQ), European Quality of Life Questionnaire (EUROQoL), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F), 100 mm-visual analogue scale (VAS) of pain, fatigue, and global health assessment, were used to evaluate HRQoL. The results were compared between patients and HCs, analyzed according to clinical course, and correlated with clinical features at the time of diagnosis. HRQoL resulted to be altered in 53 AOSD patients compared to 53 age and gender matched HCs. Many SF-36 domains differed between the 2 groups, mainly those of physical functioning which were reduced in AOSD respect to HCs. Furthermore, HAQ, FACIT-F, EuroQoL, VAS state of health, VAS pain, and VAS fatigue significantly differed between AOSD and HCs. No substantial differences were found comparing monocyclic pattern with chronic disease course. AOSD patients showed an impairment of many SF-36 domains, HAQ, FACIT-F, EuroQoL, VAS state of health, VAS pain, and VAS fatigue when compared to matched HCs, despite a low or absent clinical expressiveness; these findings were similarly retrieved in both monocyclic pattern and chronic disease course.

Objective In this study, we aimed to describe the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p < 0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Conclusion Clinical features of AOSD patients in the elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease that can produce disabling joint symptoms, adding significantly to the physical and psychosocial burden of psoriasis. Early detection is important to allow the development of an appropriate care plan to delay the onset of PsA and maximize the patient's quality of life. Our aim was to present the criteria, based on evidence and expert opinion, for a multidisciplinary approach to the management of PsA in a patient already characterized by skin manifestation. Methods: An expert panel from the principal psoriatic care units of the Campania region of Italy met to discuss their mutual experience of the multidisciplinary approach to the management of psoriatic disease and to describe an integrated dermatologic/rheumatologic approach focused on the early diagnosis, management, and treatment of PsA. Results: Two types of consultation modalities were considered most relevant to the care of patients with psoriatic disease in Italy: the parallel approach and the face-to-face care unit approach. Screening criteria for multidisciplinary care unit admission were described, with dermatologists, as the primary managers of the majority of patients with psoriasis, playing a critical role in introducing patients early on to therapy. Conclusions: An integrated management approach may enhance patient care by ensuring early diagnosis and treatment, with the potential to achieve better outcomes for both skin and musculoskeletal manifestations of psoriasis. The multidisciplinary care unit model is an effective and satisfying collaborative approach, not only optimizing outcomes and satisfaction for the patient but strengthening collaboration between the specialties.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

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.

Objectives To stratify adult-onset Still’s disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. Methods AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Results Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724 (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively]. Conclusion Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.

A growing body of evidence suggests the usability of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in treating adult-onset Still's disease (AOSD). In a multicentre "real-life" cohort, the physicians' prescribing motivations and patients' predictive characteristics of being treated with bDMARDs were assessed. Patients with AOSD, who were included in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort and treated with bDMARDs, were retrospectively assessed. Relevant data were collected by a review of clinical charts. Forty-four patients treated with bDMARDs were analysed, with slight male preponderance (52.3%) and a mean age of 39.3 ± 15.2years. All patients were treated with corticosteroids (CCSs) (38.6% with low dosage) and 93.2% were treated with synthetic DMARDs (sDMARDs). Regarding the effectiveness of the first-line bDMARD, 65.6% of patients experienced a complete remission, defined as complete disappearance of both systemic and joint symptoms and normalisation of laboratory evidence of disease. The physicians' prescribing motivations for bDMARDs were inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and occurrence of macrophage activation syndrome (MAS). Analysing patients' characteristics, chronic disease course (OR 3.09; 95%CI 1.22-7.80, p = 0.017), defined as disease with persistent symptoms, was predictive of being treated with bDMARDs, whereas age (OR 0.97, 95%CI 0.93-0.99, p = 0.048) was negatively associated, suggesting younger age as a further predictive factor. Patients with AOSD were treated with bDMARDs for inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and MAS occurrence. Younger age and chronic disease course were patients' predictive characteristics of being treated with bDMARDs.

We read with interest the recently published paper from McGonagle et al 1 analysing the role of interleukin (IL)-17A in axial spondyloarthritis and psoriatic arthritis (PsA). The meta-analysis and functional study provided by the authors highlighted the efficacy of IL-17A block by secukinumab in the treatment of PsA. However, there is no mention of the role of body mass index (BMI), if any, in influencing the clinical response to secukinumab, given the lack of published data. PsA is a chronic inflammatory arthritis burdened by a series of metabolic comorbidities. Among them, obesity is very common in PsA, with a prevalence of 27%, as confirmed by a recent Spanish work.2 Obesity in PsA has been associated with higher disease activity and a worse effectiveness of biologic treatment in PsA. This has been certainly proven for anti-tumour necrosis factor (TNF)-α as demonstrated by different studies reporting, in obese patients, a reduced treatment response and adherence. In particular, …

ObjectiveTo assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.MethodsThe predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiver-operating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively.ResultsIn assessed 147 patients with AOSD, levels of ferritin were predictive of MAS (OR: 1.971; P: 0.002; CI 95%: 1.280-3.035). The ROC curve showed that the best cut-off for ferritin was 1225 ng/ml in predicting MAS (sensitivity 88%; specificity 57%). Levels of CRP were predictive of mortality in these patients (OR: 2.155; P: 0.007; CI 95%: 1.228-3.783). The ROC curve showed that the best cut-off for CRP was 68.7 mg/L in predicting mortality (sensitivity 80%; specificity of 65%).ConclusionsWe reported the predictive role of ferritin and CRP on MAS and mortality, respectively, in a large cohort of patients with AOSD, identifying subsets at higher risk of poor prognosis. Considering that the analysis of CRP and ferritin is widely available, these results could be readily transferable into clinical practice, thus improving the management of patients with AOSD.

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. Methods: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging. Results: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes. Conclusions: Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.

Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab. Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC. Results: Of the more than 50 variables analyzed, five showed a significant correlation with DSS: ECOG PS, size of the biggest brain metastasis, number of metastatic sites, toxicity, and malignant pleural effusion. Three variables significantly correlated with TTF: malignant pleural effusion, number of metastatic sites, number of liver metastases. Malignant pleural effusion was the only variable showing a significant correlation with OR, as well as the only one correlating with all the endpoints of the study. Conclusions: This study identified clinical characteristics associated with survival and response during treatment with Nivolumab in NSCLC patients. The unfavorable association between malignant pleural effusion and objective response is a novel finding with important translational implications.

In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. We conducted a study on “post-progression” (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC). 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35–0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33–0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68–1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52–1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). Our study confirmed that in clinical practice, in case of “non-druggable” disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Objective. To investigate the role of acetylsalicylic acid (ASA) in reducing the incidence of cardiovascular (CV) events in an Italian multicentre rheumatoid arthritis (RA) inception cohort. Methods. The clinical charts of RA patients consecutively admitted to 4 Italian centres for their 1st visit from November 1, 2000, to December 31, 2015, and followed up till December 2016 were retrospectively investigated for the incidence of CV events. Patients were subdivided into two groups, namely, ASA- and non-ASA-treated groups. The Kaplan–Meier curve and log-rank test were used to investigate differences in event-free survival. Cox regression analysis was carried out to identify factors associated with CV event occurrence. Results. Seven hundred forty-six consecutive RA patients were enrolled and followed up for a median of 5.6 years (range 2.9–8.9 years). The incidence rate (IR) of CV events was 8/1000 person-years (p-ys) in the overall cohort. The IR of CV events was significantly lower in the ASA-treated group with respect to the non-ASA-treated group (IR 1.7 vs. 11.8/1000 p-ys; p=0.0002). The CV event-free rate was longer in ASA-treated patients than in non-ASA-treated patients (log-rank test 12.8; p=0.0003). At multivariable analysis, arterial hypertension (HR 9.3) and hypercholesterolemia (HR 2.8) resulted to be positive predictors and ASA (HR 0.09) and hydroxychloroquine (HCQ) (HR 0.22) to be negative predictors. Conclusion. The IR of CV events in our Italian multicentre cohort was lower than that reported in other European and non-European cohorts. Low-dose ASA may have a role in the primary prophylaxis of CV events in RA patients.

Background Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. Methods From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. Results We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21–90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p

Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC).Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis.A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS.Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.

BACKGROUND. Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS. Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS. A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status

Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (

Daniela Iacono,1 Elvira Favoino,2 Alessia Borgia,1 Serena Fasano,1 Ilenia Pantano,1 Virginia D’Abrosca,1 Giuseppe Picillo,1 Rosa Daniela Grembiale,3 Federico Perosa,2 Gabriele Valentini1 1Department of Clinical and Experimental Medicine, Rheumatology Section, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Department of Biomedical Sciences and Human Oncology (DIMO), Rheumatologic and Systemic Autoimmune Diseases Unit, University of Bari Medical School, Bari, Italy; 3Department of Medical and Surgical Sciences, University of Magna Graecia, Catanzaro, Italy Background and objective: Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients.Methods: Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts.Results: We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts.Conclusion: We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated. Keywords: rheumatoid arthritis, mortality, anti-carbamylated protein antibodies, death causes

Background: Head and neck (H&N) cancers account for about 5% of all malignant tumours. Pain is one of the most feared consequences of H&N neoplasms and is experienced by up to 80% of patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing. Nevertheless, pain is still often underestimated and undertreated. Objectives: The role of opioids in cancer pain has been well established but evidences about the role and the relative effectiveness of opioids such as fentanyl in the context of H&N cancer pain remains unclear. Methods: A literature review based on the guidance of the Centre for Reviews and Dissemination was conducted. An iterative approach was used starting with an electronic search in the MEDLINE database. The search terms ((‘Neoplasms’[Mesh]) AND ‘Head and Neck Neoplasms’[Mesh]) AND ‘Fentanyl’[Mesh] were used. Results: A total of 18 publications were found by the first performed search on PubMed. Other publications concordant with our aim were found by cross-reference. Considering inclusion and exclusion criteria for our review, eight papers resulted eligible for analysis. Conclusion: Fentanyl transdermal therapeutic system (TTS) seems to be an important option, thanks to the way of administration, the good safety and tolerability profiles to control baseline pain. For breakthrough cancer pain (BTcP), several formulations of transmucosal fentanyl are available. All the formulations seem to be active and safety but we lack head-to-head studies of fentanyl versus other strong opioids, as well as with different formulation of fentanyl, particularly for BTcP where H&N cancer population is very poorly represented.

Previous study from our group has pointed out a lower number of cardiovascular (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Clinical charts of SLE patients consecutively admitted to 5 Italian rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV events at baseline were retrospectively studied. CV cumulative incidence (ie, the proportion of patients who experienced a new CV event over the follow-up period) and CV incidence rate (ie, the number of events in the cohort divided by the total number of years at risk) were evaluated. The detected incidences were compared with those reported in SLE cohorts from other countries. The median duration of follow-up was 6 years (IQR=3-11). During the observational period, 37 (cumulative incidence=7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years. The CV cumulative incidence and incidence rate detected in our Italian cohort were lower than those from most North European and American cohorts, characterized by a high impact of traditional risk factors. Nevertheless, the cumulative incidence was similar to that reported in a Spanish cohort with a high frequency of traditional risk factors (geographic impact), while the incidence rate was only slightly higher than that in the Baltimore cohort, which is characterized by a strict follow-up of patients (medical impact). Our results confirmed that Italian lupus patients have a low incidence of CV events. Moreover, the geographic origin, traditional risk factors, and medical approach appear to have an impact on CV disease in SLE. Abbreviations: ACR = American College of Rheumatology, aPL = antiphospholipid antibody, ASA = aspirin, CV = cardiovascular, HCQ = hydroxychloroquine, SCORE = Systematic COronary Risk Evaluation, SLE = systemic lupus erythematosus.

Background Several studies showed a close relationship between Rheumatoid Arthritis (RA) and accelerated atherosclerosis [1,2]. At the best of our knowledge, no such study has been carried out in a large Italian series. Objectives To investigate the prevalence of presence of subclinical atherosclerosis and history of cardio-cerebrovascular events (CVEs), in 1266 patients consecutively admitted to Rheumatology Units throughout the whole Italy. Methods From 01/01/2015 to 31/12/2015, 1266 consecutive patients admitted to GIRRCS centres, satisfying ACR/EULAR criteria for RA were investigated for: i. traditional cardiovascular risk factors: gender, age, smoking habit, cholesterol, triglycerides, glycemia, systemic arterial hypertension (SAH), metabolic syndrome (MS), type 2 diabetes (T2D); ii. RA aspects: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage by joint X-ray, and joint surgery; iii. subclinical atherosclerosis, as assessed by ultrasound technique and/or atherosclerotic peripheral lesions; iv. history of CVEs. Results We evaluated 1176 patients out of 1266, that were investigated for both CVEs and subclinical atherosclerosis. They were mostly females (80.52%), with a median age of 60 years (range 18–91 years), a median disease duration of 12 years (range 0.8–25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity, 22.61% high disease activity. Out of 1176 patients, 217 (18%) showed evidence of subclinical atherosclerosis: a figure lower than that reported worldwide (32.7%) [2]. Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, 7 Stroke), too this figure is lower than that reported worldwide (8.5%) [3,4]. In multivariate analysis, older age (p=0.0001, OR:1.069, CI95%:1.05–1.09), MS (p=0.0001, OR:3.417, CI95%:2.16–5.40) and SAH (p=0.0001, OR:3.714, CI95%:2.23–6.17) and high disease activity (p=0.001, OR:2.117, CI95%:1.35–3.32) were significantly associated with the presence of subclinical atherosclerosis. Male gender (p=0.0001, OR:3.465, CI95%:1.94–6.185), MS (p=0.005, OR:2.542, CI95%:1.29–4.52), T2D (p=0.007, OR:2.324, CI95%:1.29–4.29) and SAH (p=0.001, OR:4.921, CI95%:2.14–11.45) and higher disease activity (p=0.003, OR:1.316, CI95%:1.15–1.68) were significantly associated with a history of CVEs. Conclusions This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events. Nonetheless, a high disease activity and presence of cardiovascular risk factors were found to play a role, similarly to other countries. References Ruscitti P, et al. PLoS One. 2017;12:e0170108. Ambrosino P, et al. Thromb Haemost. 2015;113:916–30. Solomon D et al. Ann Rheum Dis. 2010;69:1920–5. Avina-Zubieta JA, et al. Ann Rheum Dis. 2012;71:1524–9. Disclosure of Interest None declared

CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren’s syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2–11.18] vs 1.023 ng/ml [0.02–14.45], pÂ

Adult-onset Still’s disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi’s criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects. © 2016, International League of Associations for Rheumatology (ILAR).

Objectives Anaplastic lymphoma kinase ( ALK )-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who fail a 1st ALK-TKI has been poorly addressed. Materials and methods We collected the data of 69 advanced ALK -positive NSCLCs who were treated with one or more ALK-TKIs at three Italian institutions. The clinical outcome of treatment with an ALK-TKI and the patterns of treatment upon failing a 1st ALK-TKI were recorded. Results Objective response rate (ORR) and median progression-free survival (PFS) on a 1st ALK-TKI (mostly crizotinib) were 60.9% and 12 months, respectively. Of the 50 patients who progressed on a 1st ALK-TKI, 22 were further treated with a 2nd ALK-TKI (either ceritinib or alectinib), for whom an ORR of 86.4% and median PFS of 7 months, respectively, were reported. Conversely, 13 patients underwent rapid clinical/radiographic disease progression leading to death shortly after discontinuation of the 1st ALK-TKI, 7 patients were managed with a 1st ALK-TKI beyond progression, and 8 patients transitioned to other systemic treatments (mostly chemotherapy). Post-progression survival (PPS) significantly favored the 22 patients who were sequentially treated with a 2nd ALK-TKI over those who transitioned to other systemic treatments ( P =0.03), but not versus those who were treated with a 1st ALK-TKI beyond progression ( P =0.89). Conclusion Sequential treatment with a 2nd ALK-TKI is effective in patients who fail a 1st ALK-TKI. Continuous ALK-inhibition upon failing a 1st ALK-TKI may be associated with improved clinical outcome.

Summary Background We studied the use of teriparatide in postmenopausal women with severe osteoporosis. Material/Methods Two groups (A and B) of patients affected by severe osteoporosis (T-score ⩽−2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 μg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. Results Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. Conclusions The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.