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Purpose: Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is the standard treatment for locally advanced cervical cancer (LACC). Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy is an alternative for patients with stage IB2-IIB disease. Therefore the correct pre-treatment staging is essential to the proper management of this disease. Pelvic magnetic resonance imaging (MRI) is the gold standard examination but studies about MRI accuracy in the detection of lymph node metastasis (LNM) in LACC patients show conflicting data. Machine learning (ML) is emerging as a promising tool for unraveling complex non-linear relationships between patient attributes that cannot be solved by traditional statistical methods. Here we investigated whether ML might improve the accuracy of MRI in the detection of LNM in LACC patients.Methods: We analyzed retrospectively LACC patients who underwent NACT and radical hysterectomy from 2015 to 2020. Demographic, clinical and MRI characteristics before and after NACT were collected, as well as information about post-surgery histopathology. Random features elimination wrapper was used to determine an attribute core set. A ML algorithm, namely Extreme Gradient Boosting (XGBoost) was trained and validated with 10-fold cross-validation. The performances of the algorithm were assessed.Results: Our analysis included n.92 patients. FIGO stage was IB2 in n.4/92 (4.3%), IB3 in n.42/92 (45%), IIA1 in n.1/92 (1.1%), IIA2 in n.16/92 (17.4%) and IIB in n.29/92 (31.5%). Despite detected neither at pre-treatment and post-treatment MRI in any patients, LNM occurred in n.16/92 (17%) patients. The attribute core set used to train ML algorithms included grading, histotypes, age, parity, largest diameter of lesion at either pre and post-treatment MRI, presence/absence of fornix infiltration at pre-treatment MRI and FIGO stage. XGBoost showed a good performance (accuracy 89%, precision 83%, recall 78%, AUROC 0.79).Conclusions: We developed an accurate model to predict LNM in LACC patients in NACT, based on a ML algorithm requiring few easy-to-collect attributes.

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up.

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium.

COVID-19; Registries; Vaccination COVID-19; Registros; Vacunación COVID-19; Registres; Vacunació Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups. HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan-Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan-Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions.

Objectives The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. Methods An online self-reported questionnaire (March–December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. Results Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. Conclusion Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Background Despite several studies having identified factors associated with successful treatment outcomes in rheumatoid arthritis (RA), there is a lack of accurate predictive models for sustained remission in patients on biologic agents. To the best of our knowledge, no machine learning (ML) approaches apart from logistic regression (LR) have ever been tried on this class of problems. Methods In this longitudinal study, patients with RA who started a biological disease-modifying antirheumatic drug (bDMARD) in a tertiary care center were analyzed. Demographic and clinical characteristics were collected at treatment baseline, 12-month, and 24-month follow-up. A wrapper feature selection algorithm was used to determine an attribute core set. Four different ML algorithms, namely, LR, random forest, K-nearest neighbors, and extreme gradient boosting, were then trained and validated with 10-fold cross-validation to predict 24-month sustained DAS28 (Disease Activity Score on 28 joints) remission. The performances of the algorithms were then compared assessing accuracy, precision, and recall. Results Our analysis included 367 patients (female 323/367, 88%) with mean age +/- SD of 53.7 +/- 12.5 years at bDMARD baseline. Sustained DAS28 remission was achieved by 175 (47.2%) of 367 patients. The attribute core set used to train algorithms included acute phase reactant levels, Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, as well as several clinical characteristics. Extreme gradient boosting showed the best performance (accuracy, 72.7%; precision, 73.2%; recall, 68.1%), outperforming random forest (accuracy, 65.9%; precision, 65.6%; recall, 59.3%), LR (accuracy, 64.9%; precision, 62.6%; recall, 61.9%), and K-nearest neighbors (accuracy, 63%; precision, 61.5%; recall, 54.8%). Conclusions We showed that ML models can be used to predict sustained remission in RA patients on bDMARDs. Furthermore, our method only relies on a few easy-to-collect patient attributes. Our results are promising but need to be tested on longitudinal cohort studies.

Ultrasound-guided synovial tissue biopsy (USSB) may allow personalizing the treatment for patients with inflammatory arthritis. To this end, the quantification of tissue inflammation in synovial specimens can be crucial to adopt proper therapeutic strategies. This study aimed at investigating whether computer vision may be of aid in discriminating the grade of synovitis in patients undergoing USSB. We used a database of 150 photomicrographs of synovium from patients who underwent USSB. For each hematoxylin and eosin (H&E)-stained slide, Krenn’s score was calculated. After proper data pre-processing and fine-tuning, transfer learning on a ResNet34 convolutional neural network (CNN) was employed to discriminate between low and high-grade synovitis (Krenn’s score

Summary The pathogenesis of psoriatic arthritis (PsA) involves several pathways, including the CD40/CD40L signaling which promotes the release of multiple cytokines. Transmembrane CD40L is also released in soluble form (sCD40L) and phosphodiesterase 4 (PDE4) seems to be involved in its cleavage. We aimed to investigate whether apremilast, a PDE4 inhibitor, could modify circulating levels of sCD40L in PsA patients, and the possible associations of these changes with clinical response. Consecutive PsA patients starting apremilast in routine clinical practice were prospectively observed. Disease Activity of Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Score (LEI) and serum samples were collected at baseline and at 6 months. Samples were run in a Bio-Plex ProTM plate for sCD40L. To investigate the association of sCD40L level with DAPSA based minor response, low disease activity (LDA) and/or remission at 6 months of treatment, multivariate logistic regression models with backward selection (P

To compare the efficacy of Adalimumab (ADA) in noninfectious anterior uveitis (AU) and posterior segment (PS) involvement, associated with different conditions, with a focus on Behcet’s syndrome (BS). In this retrospective, multicenter post-hoc study, we evaluated the efficacy of ADA in terms of ocular control and relapses in 96 patients with AU and PS uveitis, either idiopathic (IU) or associated with BS or with other systemic disorders (OSD) (Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Vogt-Koyanagi-Harada, Inflammatory Bowel Disease), followed in three tertiary referral centers. Ninety-six patients (45 AU; 51 PS uveitis) were included. Eleven had IU, 58 BS, and 27 OSD. All patients with AU achieved complete long-term ocular control. In PS uveitis, 89%, 67% and 100% of patients with BS, IU and OSD achieved ocular control at the last follow-up (> 12 months), respectively. The lowest ocular relapse rate occurred in patients with AU with BS (1/13) or IU (0/2). ADA accounted for long-term disease control, and no predictors of ocular control and relapse were identified; particularly, ocular relapses seemed not related to systemic ones. Macular edema resolved in 75% and 67% of PS uveitis with BS and IU, respectively. ADA controls both anterior and posterior uveitis, with an efficacy similar in IU, BS and OSD patients. In BS, the efficacy of ADA seems to be independent of demographic and clinical characteristics, and ocular relapses mostly occurred independently from systemic ones. Based on our results, ADA may represent a valid alternative in anterior refractory uveitis.

Scanty data on the anti- SARS-CoV-2 IgG level decay after two-dose BNT162b2 vaccination have been published in patients with psoriatic arthritis (PsA) on TNF inhibitors (TNFi). Similarly, no reports on the immunogenicity of a booster dose in such patients have been provided yet.We aimed to investigate the IgG level decay after two-dose BNT162b2 vaccination and the immunogenicity and safety of the booster dose in PsA patients on TNFi.Forty patients with classified PsA on TNFi undergoing booster dose with the BNT162b2 mRNA SARS- CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the third shot, serum IgG levels against SARS-CoV-2 (Abbott®ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score-matching. Student's t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response.Even though the decay of IgG levels showed similar magnitude between groups, PsA patients had a lower IgG level than matched controls at 4 months after two-dose vaccination (2009.22±4050.22 vs. 6206.59±4968.33 AU/mL, respectively p=0.0006). Booster dose restored IgG levels to a similar extent in both groups (15846.47±12876.48 vs. 20374.46±12797.08 AU/ml p=0.20, respectively). Clinical Disease Activity Index (CDAI) did not change before and after vaccination (6.68±4.38 vs. 4.95±4.20, p=0.19).A BNT162b2 booster dose should be recommended in PsA patients on TNFi as its administration restores anti-SARS-CoV-2 IgG levels similar to healthy individuals.

Few studies compared adalimumab to other targeted therapies in head-to-head randomized clinical trials (RCTs) for rheumatoid arthritis (RA), but multiple comparisons are not available. This Bayesian Network Meta-Analysis evaluated which targeted therapy is more likely to achieve ACR50 response with good safety at 24 weeks of treatment in RA. A systematic literature review was conducted for head-to-head phase 3 RCTs that compared adalimumab to other targeted therapies in combination with methotrexate (MTX) or as monotherapy to treat RA patients, and searched through MEDLINE, EMBASE, Cochrane Library and Clinicaltrial.gov. The outcomes of interest were ACR50 response and withdrawals due to adverse events at 24 weeks. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses, using a random effect model. Sixteen studies were included in the analysis. The most favorable SUCRA for the ACR50 response rate at 24 weeks of treatment in combination with MTX was ranked by upadacitinib, followed by baricitinib, tofacitinib and filgotinib. As monotherapy, the highest probability was ranked by tocilizumab followed by sarilumab. No significant differences in safety profile among treatment options were found. Jak-inhibitors in combination with MTX and interleukin-6 antagonism as monotherapy showed the highest probability to achieve ACR50 response after 24 weeks of treatment. None of assessed targeted therapies were associated to risk of withdrawal due to adverse events. Key messages: Direct and indirect comparison between adalimumab and other targeted therapies demonstrated some differences in terms of efficacy that may help to drive RA treatment. Jak-inhibitors and interleukine-6 antagonists ranked as first in the probability to achieve ACR50 response after 24 weeks of treatment in combination with methotrexate or monotherapy, respectively.

Over the years, increasing information has been asked of the pathologist: we have moved from a purely morphological diagnosis to biomolecular and genetic studies, which have made it possible to implement the use of molecular targeted therapies, such as anti-epidermal growth factor receptor (EGFR) molecules in EGFR-mutated lung cancer, for example. Today, next generation sequencing (NGS) has changed the approach to neoplasms, to the extent that, in a short time, it has gained a place of absolute importance and diagnostic, prognostic and therapeutic utility. In this scenario, formaldehyde-fixed and paraffin-embedded (FFPE) biological tissue samples are a source of clinical and molecular information. However, problems can arise in the genetic material (DNA and RNA) for use in NGS due to fixation, and work is being devoted to possible strategies to reduce its effects. In this paper, we discuss the applications of FFPE tissue samples in the execution of NGS, we focus on the problems arising with the use of this type of material for nucleic acid extraction and, finally, we consider the most useful strategies to prevent and reduce single nucleotide polymorphisms (SNV) and other fixation artifacts.

BackgroundScanty data on the immunogenicity of the BNT162b2 vaccine in patients with psoriatic arthritis (PsA) on Tumor Necrosis Factor inhibitors (TNFi) have been published.ObjectiveTo investigate the humoral response to BNT162b2 vaccination patients with PsA on TNFi, comparing immunogenicity with healthy controls.MethodsForty patients with classified PsA on TNFi undergoing vaccination with the BNT162b2 mRNA SARS-CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the second shot, serum IgG levels against SARS-CoV-2 (Abbott ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued throughout the whole period, whereas methotrexate (MTX) was discontinued for 1 week after each shot in those on combination therapy. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score matching; any of them was taking medication.Student’s t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response.ResultsClinical Disease Activity Index did not change before and after vaccination (7.06±5.23 to 7.10±5.27, p=0.92).Patients with PsA achieved a positive anti-SARS-CoV-2 IgG level with a mean (±SD) of 13794.44±15 815.42 AU/mL. Although lower, the antibody level was not significantly different from matched controls (19227.4±11.8460.45 AU/mL, p=0.08). In the overall sample, those on MTX (12/80, 15%) had a trend toward lower immune response (p=0.07); glucocorticoid therapy (11/80, 13.8%) predicted lower antibody levels (p=0.04).ConclusionsContinuing TNFi in patients with PsA throughout the vaccination did not hamper immunogenicity.

Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.

Objectives To evaluate the impact of FM on the clinical outcomes of biologics in patients with PsA in real life. Methods FM was diagnosed according to current criteria among PsA patients starting a first biologic drug from 2010 through 2017. At each visit, disease activity of PsA (DAPSA), minimal disease activity (MDA), HAQ, rate of patients achieving DAPSA-based low disease activity (LDA) or remission, and MDA were evaluated. Lost patients or those not achieving the target were imputed as non-responders. The drug survival was evaluated by Kaplan–Meyer analysis. Estimated hazard ratios (HRs) of discontinuing therapy or achieving MDA were assessed by multivariate regression models. Results A total of 238 patients, of whom 58 had also FM, started a first biologic drug. Compared with no-FM PsA, FM PsA patients were more frequently female (P = 0.0001) with polyarticular subset (P = 0.0001), and with higher mean BMI (P = 0.006). Drug survival was significantly lower in FM PsA (50%, mean 32 months) than in no-FM PsA (74%, mean 42 months, P = 0.0001). Rates of remission/LDA and MDA were significantly lower in FM PsA at 3, 6, 12 and 24 months (P < 0.001). Remission in FM PsA was negligible (3.4% and 0% at 3 and 6 months, respectively). Negative predictors of drug discontinuation were no FM (HR 0.51) and normal weight (HR 0.29), while no FM (HR 2.54) and male sex (HR 1.58) were positive predictors of long-standing MDA. Conclusions Comorbid FM, along with female gender and obesity seem to be the worst combination of negative prognostic factors in PsA.

The current paradigm in the management of rheumatoid arthritis (RA) is to treat patients in the early stage of the disease (ERA). Previous meta-analysis-based mixed treatment comparisons (MTCs), aimed to identify the most effective drugs in ERA, are biased by the wide “window” of early definition, ranging from 6 months to 2 years. The aim of this study was to estimate through a Bayesian Network Meta-Analysis which biologics or small molecules are more likely to achieve a 1-year good clinical response in ERA patients with disease duration

Background: Systemic sclerosis (SSc) is a rare connective tissue disease that can affect different organs and has extremely heterogenous presentations. This complexity makes it difficult to perform an early diagnosis and a subsequent subclassification of the disease. This hinders a personalized approach in clinical practice. In this context, machine learning (ML), a branch of artificial intelligence (AI), is able to recognize relationships in data and predict outcomes. Methods: Here, we performed a narrative review concerning the application of ML in SSc to define the state of art and evaluate its role in a precision medicine context. Results: Currently, ML has been used to stratify SSc patients and identify those at high risk of severe complications. Additionally, ML may be useful in the early detection of organ involvement. Furthermore, ML might have a role in target therapy approach and in predicting drug response. Conclusion: Available evidence about the utility of ML in SSc is sparse but promising. Future improvements in this field could result in a big step toward precision medicine. Further research is needed to define ML application in clinical practice.

The oral microbiome is receiving growing interest from the scientific community, as the mouth is the gateway for numerous potential etiopathogenetic factors in different diseases. In addition, the progression of niches from the mouth to the gut, defined as “oral–gut microbiome axis”, affects several pathologies, as rheumatic diseases. Notably, rheumatic disorders (RDs) are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. In this review, we examine evidence which supports a role for the oral microbiome in the etiology and progression of various RDs, including rheumatoid arthritis (RA), Sjogren’s syndrome (SS), and systemic lupus erythematosus (SLE). In addition, we address the most recent studies endorsing the oral microbiome as promising diagnostic biomarkers for RDs. Lastly, we introduce the concepts of artificial intelligence (AI), in particular, machine learning (ML) and their general application for understanding the link between oral microbiota and rheumatic diseases, speculating the application of a possible AI approach-based that can be applied to personalized medicine in the future.

The objective is to evaluate the effectiveness of a spacing strategy of bDMARDs in a cohort of selected patients in disease remission or low-disease activity (LDA) without glucocorticoids affected with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). This was a single-centre study carried out on patients prospectively enrolled in the biologic Apulian registry. Patients whose disease was in remission or LDA without taking glucocorticoids during the previous 6 months and who had agreed to increase the time interval between bDMARD doses were included in this study. Demographic and clinical characteristics were recorded at baseline and at 3, 6 and 12 months of follow-up. Endpoint of the study was the survival of spacing doses in the time lag of the study. Failure of spacing was defined as the first flare of disease. Thirty-seven RA, 28 PsA and 20 axSpA patients underwent bDMARD spacing according to a local strategy. During the follow-up, 5 RA, 6 PsA and 4 axSpA patients had a joint flare, but further 5 PsA patients manifested a skin relapse. Global persistence was 86.5% for RA (MST = 41 (95% CI: 37-45) months) and 80% for axSpA patients (MST = 36 (95% CI: 31-42) months). PsA patients showed a lower persistence, being of 60.7% (MST = 30 (95% CI: 23-36) months) (log-rank test, p = 0.03). Dose reduction by spacing bDMARD doses may be a feasible approach in patients with persistent remission/LDA activity. However, PsA patients might have greater odds of spacing failure because of skin psoriasis relapse. Key Points • Spacing of bDMARDs may be a feasible strategy for some patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis who achieve the target and withdrawn glucocorticoids. • Psoriatic arthritis patients showed lower persistence because of both articular and skin relapses.

BACKGROUND One of the most intriguing conundrums in patients with rheumatoid arthritis (RA) is the lack of correlation between cholesterol levels and cardiovascular (CV) events, mining the reliability of plasmatic lipid levels in estimating the CV risk. High-density lipoprotein cholesterol efflux capacity (HDLc-EC) directly indicates the functional ability of HDL to scavenge cholesterol from vascular wall and may provide better information on the atherogenic risk. The aim of this study was to examine the effects of different disease-modifying antirheumatic drugs on HDLc-EC in RA. METHODS Consecutive RA patients treated with different biologic disease-modifying antirheumatic drugs or methotrexate monotherapy were longitudinally observed. Demographic and clinical features as well as lipid profile were recorded at baseline, 24-week, and 52-week follow-up. At the same time points, HDLc-EC was evaluated using J771 macrophages and a fluorometric assay. RESULTS We analyzed 100 RA patients on methotrexate, infliximab, tocilizumab, abatacept, or rituximab. No significant changes in the lipoprotein levels were detected, whereas the mean HDLc-EC statistically increased from baseline (22.5% ± 4.8%) to 24 weeks (24.5% ± 5.7%; p < 0.001) and 52 weeks (25.1% ± 5.9%; p < 0.001). Patients on tocilizumab showed the highest increase in HDLc-EC, already at 24 weeks. Patients on treatment with infliximab or rituximab showed a significant increase in HDLc-EC at 52 weeks. No significant changes were detected in abatacept and methotrexate groups. CONCLUSIONS Some treatments may impact cholesterol reverse transport in RA. The improved HDLc-EC, independently from lipid levels, may be one of the missing links between inflammation, lipids, and CV risk in RA.

EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.

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.