Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Explainable artificial intelligence for microbiome data analysis in colorectal cancer biomarker identification.

Background: Colorectal cancer (CRC) is a type of tumor caused by the uncontrolled growth of cells in the mucosa lining the last part of the intestine. Emerging evidence underscores an association between CRC and gut microbiome dysbiosis. The high mortality rate of this cancer has made it necessary to develop new early diagnostic methods. Machine learning (ML) techniques can represent a solution to evaluate the interaction between intestinal microbiota and host physiology. Through explained artificial intelligence (XAI) it is possible to evaluate the individual contributions of microbial taxonomic markers for each subject. Our work also implements the Shapley Method Additive Explanations (SHAP) algorithm to identify for each subject which parameters are important in the context of CRC. Results: The proposed study aimed to implement an explainable artificial intelligence framework using both gut microbiota data and demographic information from subjects to classify a cohort of control subjects from those with CRC. Our analysis revealed an association between gut microbiota and this disease. We compared three machine learning algorithms, and the Random Forest (RF) algorithm emerged as the best classifier, with a precision of 0.729 ± 0.038 and an area under the Precision-Recall curve of 0.668 ± 0.016. Additionally, SHAP analysis highlighted the most crucial variables in the model's decision-making, facilitating the identification of specific bacteria linked to CRC. Our results confirmed the role of certain bacteria, such as Fusobacterium, Peptostreptococcus, and Parvimonas, whose abundance appears notably associated with the disease, as well as bacteria whose presence is linked to a non-diseased state. Discussion: These findings emphasizes the potential of leveraging gut microbiota data within an explainable AI framework for CRC classification. The significant association observed aligns with existing knowledge. The precision exhibited by the RF algorithm reinforces its suitability for such classification tasks. The SHAP analysis not only enhanced interpretability but identified specific bacteria crucial in CRC determination. This approach opens avenues for targeted interventions based on microbial signatures. Further exploration is warranted to deepen our understanding of the intricate interplay between microbiota and health, providing insights for refined diagnostic and therapeutic strategies.

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry.

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

Organ damage is a major determinant of work productivity impairment in Behçet's Syndrome: a post-hoc analysis of the BODI validation study.

OBJECTIVES: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage. METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis. RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (ß 0.225); female sex (ß 0.260), physician global assessment of disease activity (ß 0.502) and an increased BODI score (ß 0.166 for 1-point increase) with presenteeism; fibromyalgia (ß 0.246), physician global assessment (ß 0.469), and musculoskeletal damage (ß 0.325) with overall work impairment. CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

Effectiveness of biological targeted therapies may discriminate seronegative from seropositive rheumatoid arthritis.

OBJECTIVE: To assess the real-world effectiveness of targeting biologic drugs (bDMARD) in rheumatoid arthritis (RA) patients negative for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). METHODS: We retrospectively selected 81 seronegative and 404 seropositive RA patients receiving treatment with abatacept, anti-tumor necrosis factor (TNF) alpha, or tocilizumab. Effectiveness was evaluated by analyzing drug survival using Kaplan-Meyer analysis over 10-year follow-up. Survival rates were compared by log rank test, and hazard ratios (HRs) of therapy discontinuation were estimated through multivariate Cox-regression. RESULTS: Clinical characteristics were similar between the two groups, except for a significantly higher percentage of inadequate responders to prior bDMARDs in the seronegative RA patients (p= 0.02). Among seronegative RA, tocilizumab demonstrated a survival rate of 73.9% with a mean survival time (MST) of 76.8 months (95% CI 61-92), which was significantly higher than abatacept (37.5%, MST 37.1 months (95% CI 22-51; p= 0.01). Anti-TNF alpha therapy fell in the middle (50.0%, MST 63.5 months (95% CI 47-79) but the difference was not significant. Nevertheless, seropositive RA patients did not show significantly different drug survival rates. Negative predictors of drug discontinuation were RF/ACPA positivity (HR 0.56) and sex male (HR 0.58), but treatment with abatacept (HR 1.88) or anti-TNF alpha (HR 1.79), no co-therapy with cDMARD (HR 1.74), absence of bone erosions (HR 1.41), and higher HAQ (HR 1.58) were positive predictors. CONCLUSIONS: To confirm these preliminary findings and to explore the hypothesis of a distinctive therapeutic algorithm in seronegative RA, prospective studies on larger cohorts are needed.

Axial spondyloarthritis in patients with recurrent fever attacks: data from the AIDA network registry for undifferentiated autoInflammatory diseases (USAIDs).

Beckground: Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Materials and methods: Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. Results: A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents. Conclusion: Signs and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

INTRODUCTION: Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. METHODS: This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. RESULTS: Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. CONCLUSIONS: ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet's Syndrome and Psoriatic Arthritis.

Behçet's syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α-a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases-to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.

Anti-SARS-CoV-2 antibody decay after vaccination and immunogenicity of the booster dose of the BNT162b2 mRNA vaccine in patients with psoriatic arthritis on TNF inhibitors.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.

Accrual of organ damage in Behçet's syndrome: trajectory, associated factors, and impact on patients' quality of life over a 2-year prospective follow-up study.

BACKGROUND: This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet's syndrome (BS) over 2 years of follow-up. METHODS: Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. RESULTS: During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07-1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09-9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08-0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL. CONCLUSION: In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.

A Machine Learning Approach to Predict Remission in Patients With Psoriatic Arthritis on Treatment With Secukinumab.

Background: Psoriatic Arthritis (PsA) is a multifactorial disease, and predicting remission is challenging. Machine learning (ML) is a promising tool for building multi-parametric models to predict clinical outcomes. We aimed at developing a ML algorithm to predict the probability of remission in PsA patients on treatment with Secukinumab (SEC). Methods: PsA patients undergoing SEC treatment between September 2017 and September 2020 were retrospectively analyzed. At baseline and 12-month follow-up, we retrieved demographic and clinical characteristics, including Body Mass Index (BMI), disease phenotypes, Disease Activity in PsA (DAPSA), Leeds Enthesitis Index (LEI) and presence/absence of comorbidities, including fibromyalgia and metabolic syndrome. Two random feature elimination wrappers, based on an eXtreme Gradient Boosting (XGBoost) and Logistic Regression (LR), were trained and validated with 10-fold cross-validation for predicting 12-month DAPSA remission with an attribute core set with the least number of predictors. The performance of each algorithm was assessed in terms of accuracy, precision, recall and area under receiver operating characteristic curve (AUROC). Results: One-hundred-nineteen patients were selected. At 12 months, 20 out of 119 patients (25.21%) achieved DAPSA remission. Accuracy and AUROC of XGBoost was of 0.97 ± 0.06 and 0.97 ± 0.07, overtaking LR (accuracy 0.73 ± 0.09, AUROC 0.78 ± 0.14). Baseline DAPSA, fibromyalgia and axial disease were the most important attributes for the algorithm and were negatively associated with 12-month DAPSA remission. Conclusions: A ML approach may identify SEC good responders. Patients with a high disease burden and axial disease with comorbid fibromyalgia seem challenging to treat.

Immunogenicity of BNT162b2 mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis on TNF inhibitors.

BACKGROUND: Scanty data on the immunogenicity of the BNT162b2 vaccine in patients with psoriatic arthritis (PsA) on Tumor Necrosis Factor inhibitors (TNFi) have been published. OBJECTIVE: To investigate the humoral response to BNT162b2 vaccination patients with PsA on TNFi, comparing immunogenicity with healthy controls. METHODS: Forty 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. RESULTS: Clinical 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). CONCLUSIONS: Continuing TNFi in patients with PsA throughout the vaccination did not hamper immunogenicity.

Anakinra effectiveness in refractory polyserositis: An Italian multicenter study.

OBJECTIVES: Polyserositis is an inflammatory condition involving different serosal membranes at the same time, specifically the pericardium, pleura, and peritoneum with exudates in the respective cavities. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids may be effective in patients with polyserositis, but relapses often occur when these drugs are tapered or discontinued. The interleukin (IL)-1 receptor antagonist anakinra has shown a beneficial effect in idiopathic recurrent pericarditis, mostly in unresponsive patients who develop steroid dependence and/or colchicine resistance. To date, there are no data suggesting the best therapy for managing acute episodes and/or relapses of polyserositis. On this basis, we performed a retrospective study aimed at evaluating the effectiveness and safety profile of anakinra in treating patients with refractory polyserositis. METHODS: Patients with idiopathic polyserositis or rheumatic diseases presenting inflammation of 2 or more serous membranes were included. Serositis had to be confirmed by imaging tests comprising either echocardiography, abdominal ultrasound, chest or abdomen computed tomography and/or chest x-ray scan. We included patients with polyserositis who started anakinra from January 2011 to January 2019 due to a poorly controlled disease despite treatment with NSAIDs, conventional immunosuppressant drugs, or the need to minimize oral corticosteroids intake. Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and imaging tests, were recorded to monitor serositis at baseline and either at 3, 6 and 12-month follow-up. Patients with malignancies and infectious diseases were excluded from the analysis. RESULTS: Forty-five patients with recurrent polyserositis (23 women) (mean age 43.2±15.8 years and mean disease duration 23.1±28 years) were analysed. Polyserositis was idiopathic in 26 (57.8%) patients. Thirteen patients suffered from autoinflammatory diseases, whereas 6 were affected by autoimmune diseases. Combination treatment with colchicine and NSAIDs at anakinra baseline was administered in 38/45 (84.4%) and 37/45 (82.2%) patients, respectively. After starting anakinra, 84.5% of patients experienced a resolution of serositis with a dramatic decrease in ESR and CRP (P<0.001, for both) already at 3 months, furthermore the same beneficial effect was observed up to 12 months. No relapse was seen at 3 months, whereas the median number of relapses at 6 and 12 months was 0 (interquartile range 0-1). Glucocorticoids were discontinued in 22/45 (48.9%) patients already after 3 months (P<0.001). After 12 months 32/37 (86.5%) patients were steroid-free. Similarly, NSAIDs use significantly was decreased at 3 months (7/45 [15.6%] patients, P<0.001), whereas at 12-month follow-up no patient was on NSAIDs. Urticarial rashes at anakinra injection site occurring in 3 patients were the most common adverse events. CONCLUSIONS: Anakinra appeared to be a safe and useful therapeutic choice for patients refractory to optimal anti-inflammatory therapy (NSAIDs, colchicine and corticosteroids), allowing not only a dramatic reduction of recurrences but also of corticosteroids use. Anakinra was effective both in the idiopathic forms of polyserositis and in those with an underlying rheumatic disease, suggesting a common pathogenic pathway leading to serositis onset.

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study.

OBJECTIVE: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. METHODS: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. RESULTS: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). CONCLUSION: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study.

Objectives: Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. Methods: High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. Results: We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36-120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56-55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05-0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06-0.82) and the flatness (HR 0.42, 95% CI 0.18-0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82-2.83) was also retained as a confounder. Conclusion: Radiomic analysis may predict RA-ILD patients' mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease.

Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome-Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network.

Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response. Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers. Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001-0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301-0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed. Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.