Objective Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterised by a primary pathogenic involvement of interleukin (IL)-1. Therefore, IL-1 blockers are currently considered the optimal therapeutic option for SchS patients. However, while IL-1 blockers are first-line for SchS, long-term real-world evidence is limited by the rarity of the disease. We assessed the long-term effectiveness and safety of the IL-1 inhibitors anakinra and canakinumab used in SchS, also looking for variables capable of affecting global effectiveness and drug retention over time. Methods Data analysed in this study were drawn from the international AutoInflammatory Disease Alliance (AIDA) Registry dedicated to SchS. Results 28 SchS patients corresponding to 37 treatment lines were included in the study. Complete and partial responses occurred in 73.1% and 29.9% of anakinra-treated patients, and 66.8% and 33.3% with canakinumab. The overall anakinra and canakinumab drug retention rates at 12-, 36-, and 60-month follow-up were 85.6%, 81.7% and 64.7%, respectively; the probability of discontinuing IL-1 inhibitors at 12-, 36-and 60 months due to loss of effectiveness was 9.6%, 13.7% and 24.5%, respectively. The maximum IgG M-protein levels were found to be significantly higher in patients achieving partial response compared to those benefiting from complete response (p=0.032). Lymphadenopathy independently predicted anti-IL-1 discontinuation due to loss of effectiveness (HR 7.78, 95% CI: 1.27-47.9; p=0.027). Conclusion The present study confirms the high effectiveness of IL-1 inhibitors in controlling SchS, including the complete and partial response rates and the long-term survival. Elevated IgG M-protein levels and the presence of lymphadenopathy should be considered as potential indicators for identifying patients more likely to exhibit a partial response and a possible loss of treatment efficacy.

OBJECTIVES:To assess long-term organ damage and its accrual in a real-life cohort of Behçet's syndrome (BS) patients using the Behçet's Syndrome Overall Damage Index (BODI), identifying predictors of damage at diagnosis and factors associated with its accrual during follow-up. METHODS:This single-centre retrospective study included 155 BS patients followed for at least six months. Organ damage was assessed at diagnosis and at various timepoints. Damage was defined as a BODI score ≥1 and damage accrual as an increase (ΔBODI) ≥1 between timepoints. Multivariable logistic regressions were used to identify predictors of damage. RESULTS:At diagnosis, 31.1% of patients already exhibited damage. This prevalence progressively increased to 53.8% at 10-year follow-up, with 39.7% of patients experiencing damage accrual. Pre-existing damage at diagnosis was a risk factor for faster accumulation of new damage. Multivariable analysis identified non-Italian origin and older age at diagnosis as independent predictors of damage at baseline. Notably, older age also remained a significant predictor of damage accrual during the 10-year follow-up. Furthermore, the accumulation of new damage during the disease course was associated with more frequent corticosteroid treatment. CONCLUSIONS:Organ damage in BS is associated with different factors depending on the disease stage: while demographic features, particularly non-Italian origin and older age, significantly predict the presence of damage at diagnosis, older age and corticosteroid therapy are associated with damage accrual in the long-term. These findings highlight the importance of age-targeted clinical monitoring and of steroid-sparing strategies and early intervention in high-risk demographic groups to mitigate irreversible disability.

OBJECTIVES:To assess the effectiveness of canakinumab (CAN) in controlling clinical and laboratory inflammation by achieving complete control of cardinal disease manifestations and full normalization of laboratory inflammatory markers. METHODS:Data were obtained from the international AutoInflammatory Disease Alliance (AIDA) network registry, dedicated to monogenic autoinflammatory diseases. The assessment included both retrospective and prospective real-world data. RESULTS:In total, 158 FMF patients treated with CAN were enrolled. Complete clinical-laboratory response was observed in 45.6% of patients at 3 months, 58.6% at 12 months and 55.2% at the last follow-up, after a mean treatment duration of 45 months. Partial response occurred in 16.5%, 12.5% and 16.8% at the same timepoints, respectively. Complete absence of clinical manifestations was observed in more than 80% of patients at each timepoint. Inflammatory markers normalized significantly by the 3-month assessment. The probability of achieving and maintaining complete response and full laboratory control appeared higher in patients reaching these outcomes by 3 months, although it remained substantial in other patients as well. Complete response was associated with a relapsing-remitting disease course and fewer annual attacks. Nearly all patients maintained stable organ damage scores, and therapy discontinuation due to inefficacy was rare (≤6%). CONCLUSION:CAN is effective in achieving rapid and sustained clinical and laboratory control in FMF, including stringent endpoints of complete response. Early effectiveness may favour better long-term outcomes, but delayed achievement of complete response and full laboratory control is not uncommon. This study confirms CAN as an effective, and durable therapeutic option in FMF.

ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.

Orbital inflammation is the most common presentation of VEXAS, with any orbital structure potentially affected. Non-sight-threatening and uncomplicated anterior non-granulomatous uveitis and anterior diffuse scleritis follow in frequency, along with episcleritis. Ophthalmic involvement was significantly associated with relapsing polychondritis (p = 0.014), with an increased chance of a fatal outcome (RR 5.87, p = 0.016) and independently predicts a higher mortality rate (OR 3.72, p = 0.026). Treatment of ophthalmic involvement showed full or partial response to glucocorticosteroids alone in 66.7% of cases. Ophthalmic involvement is common in VEXAS syndrome and signals a poorer prognosis in terms of mortality, highlighting the need for close monitoring.

IntroductionRecurrent febrile episodes account for one of the most frequent symptoms observed in Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome and a key target for therapeutic intervention. Therefore, this study aims at investigating the association between recurrent febrile episodes and specific clinical manifestations, mortality and response to treatment.MethodsData were obtained from the international AutoInflammatory Disease Alliance (AIDA) Network registry and analyzed using a Bayesian statistical approach. Posterior probabilities [P(β)] were calculated to assess the likelihood that fever was associated with clinical, laboratory, genetic, and therapeutic features.ResultsIn total, 87 VEXAS patients were enrolled, 65 (74.7%) of whom suffered from recurrent fever episodes. Fever episodes showed a significant association with patients’ mortality [P(β): 99.41%], as well as with major inflammatory organ involvement, including cardiac [P(β): 99.99%], lung [P(β): 99.98%], and gastrointestinal [P(β): 97.5%] involvement. The occurrence of recurrent fever episodes was associated with a negligible probability of both complete response and treatment failure [P(β) <2.5%], instead favoring a partial response [P(β) >97.5%] to conventional disease modifying anti-rheumatic drugs, Janus Kinases inhibitors, and tocilizumab. For temperatures exceeding 40 °C, using anti-interleukin-1 agents was associated with a high probability of treatment failure [P(β): 99.3%].Conclusionsfebrile episodes are associated with more severe pattern of organ involvement and, accordingly, to death. Furthermore, febrile episodes could correlate with differential therapeutic responsiveness, thereby potentially serving as a valuable marker to guide the treatment strategies in VEXAS patients.

Objectives To evaluate whether early canakinumab initiation may provide treatment advantages in Still’s disease (SD) patients, particularly in terms of therapy discontinuation due to long-term disease remission, glucocorticoid sparing effect, and increase in the frequency of monocyclic disease course rather than a polycyclic or chronic articular pattern. Methods SD patients treated with canakinumab were grouped according to time between disease onset and canakinumab initiation (≤3 months vs. >3 months). Patients were enrolled from the international AutoInflammatory Disease Alliance (AIDA) Network registry for SD. Results Overall, 190 patients were enrolled, 35 (19%) treated with canakinumab within three months from SD onset and 155 (82%) starting canakinumab later. Glucocorticoids use decreased more rapidly in patients receiving canakinumab within 3 months from SD onset than among patients treated later, with reductions of 50% vs 6% at month 3 (p=0.0001), and 75% vs 32% at month 6 (p=0.004). In logistic regression analysis, canakinumab initiation within 3 months from disease onset was significantly associated with treatment discontinuation due to long-term remission (OR 4.83, 95% CI 1.08-23.19; p=0.04). A monocyclic course occurred in 49% of patients starting canakinumab ≤3 months versus 8% starting later (p<0.0001). Starting canakinumab within 3 months from disease onset was significantly associated with a monocyclic disease course compared with the chronic-articular (RRR 4.43, 95% CI 1.12-17.60; p=0.034) and polycyclic courses (RRR 8.97, 95% CI 1.29-62.3; p=0.03). Conclusions Early canakinumab initiation is associated with treatment discontinuation due to long-term remission and appears linked to a greater frequency of a monocyclic disease course.

Background:A substantial overlap in demographic, clinical, and laboratory features can complicate the differential diagnosis between Schnitzler's syndrome and VEXAS syndrome. The present study was undertaken to identify clinical and laboratory parameters that should raise suspicion for VEXAS syndrome among patients previously diagnosed with, or under evaluation for, Schnitzler's syndrome. Methods:Data from male-only patients with Schnitzler's syndrome or VEXAS syndrome were obtained from international AIDA Network registries. Subjects with Schnitzler's syndrome were compared to VEXAS patients with urticarial skin manifestations resembling cutaneous features typically observed in Schnitzler's syndrome. Results:A total of 19 VEXAS patients and 18 patients with Schnitzler's syndrome were enrolled. At univariate binary logistic regression, the diagnosis of VEXAS syndrome was associated with the age at disease onset (OR = 1.08, 95% CI. 1.01-1.16, p = 0.02), hemoglobin levels (OR = 0.44, 95% CI. 0.26-0.77, p = 0.003), anemia (OR = 13.9, 95% CI. 3.4-5.7, p = 0.02), leucocytosis (OR = 0.04, 95% CI. 0.06-0.22, p < 0.001), lymphadenopathy (OR = 7.8, 95% CI. 1.41-45.4, p = 0.02), and thrombocytopenia (OR = 13.5, 95% CI. 1.47-123.7, p = 0.02). In the multivariable logistic regression analysis with the stepwise forward selection approach, the diagnosis of VEXAS syndrome was significantly associated with the age at disease onset (OR: 1.13, 95% CI: 1.02-1.30, p = 0.04) and the presence of lymphadenopathy (OR: 67.49, 95% CI: 5.36-3284.89, p = 0.007), while thrombocytopenia showed a trend toward statistical significance (OR: 12.02, 95% CI: 1.07-315.86, p = 0.06). Conclusions:Patients with lymphadenopathy, thrombocytopenia, anemia, particularly in older age and in the absence of leucocytosis, are more likely to be affected by VEXAS syndrome rather than Schnitzler's syndrome.

OBJECTIVES:The progression of Behçet's disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. METHODS:Patients' data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. RESULTS:A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22-0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44-113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1-5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15-7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22-11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08-7.58, P = 0.03). CONCLUSION:A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.

ObjectivesThis study aims to explore the application of machine learning techniques in assessing macrophage activation syndrome (MAS) in Still’s disease.MethodsA multicenter, observational, prospective study was conducted, including patients with Still’s disease enrolled in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD Study Group and the AutoInflammatory Disease Alliance (AIDA) Network Still’s Disease Registry.ResultsA total of 737 patients (age: 35.5 ± 17.8, male sex: 44.7%) with Still’s disease were assessed; 11.4% were affected by MAS, and 3% had a poor prognosis. First, random forest imputation was applied to the original dataset. Subsequently, a machine-learning-driven assessment was developed to explore MAS occurrence. Collectively, regression models, an exploration decision tree, and a random forest were applied, suggesting the importance of ferritin, age, C-reactive protein (CRP), and systemic score. A logistic regression model accounting for data leakage concerns was then generated using these variables, and missing values were imputed using random forest imputation. This analysis supported the role of the selected variables, which were further combined across different clinical scenarios to estimate the probability of MAS. The highest risk of MAS was estimated for patients simultaneously characterized by age ≥ 45 years, ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and a systemic score ≥ 7, corresponding to a 34.7% probability of MAS, as well as for those characterized by ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and systemic score ≥ 7, corresponding to a 33.5% probability of MAS.ConclusionsA machine-learning-driven prediction of MAS was explored in Still’s disease, highlighting the importance of age of onset, hyperferritinaemia, increased CRP, and multiorgan involvement. A combination of these features may suggest a clinician-friendly algorithm for stratifying the probability of MAS during Still’s disease.

BACKGROUND:VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an acquired autoinflammatory disorder characterized by severe chronic inflammation and an increased occurrence of hematologic neoplasms. Although chronic inflammation is a well-established risk factor for cancer, the specific contribution of UBA1 gene mutations to tumorigenesis remains unclear. Therefore, this study aimed to evaluate the overall cancer risk in patients with VEXAS syndrome, including both hematologic and non-hematologic neoplasms. METHODS:The relative risk (RR) of cancer was compared between VEXAS patients and a control cohort comprising individuals with Still's disease, Behçet's disease, and Schnitzler's syndrome. Logistic regression analysis was performed to identify variables potentially associated with cancer development. Patient's data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries for VEXAS syndrome, Still's disease, Behçet's disease, and Schnitzler's syndrome. RESULTS:Ninety-six VEXAS patients and 2181 controls were enrolled. To minimize selection bias, only subjects aged >60 years were included, yielding 90 and 174 individuals in the exposed and control groups, respectively. The overall RR for cancer in VEXAS patients was 1.93 (95 % Confidence Interval [C.I.] 1.03-3.60, p = 0.036). Logistic regression analysis identified associations between cancer development and relapsing polychondritis (RR = 2.67, 95 %C.I. 1.22-10.64, p = 0.01), the p.Met41Thr mutation (RR = 3.33, 95 %C.I. 1.29-17.33, p = 0.02), elevated serum erythrocyte sedimentation rate (RR = 1.02, 95 %C.I. 1.01-1.05 p = 0.01), and lactate dehydrogenase (RR = 1.02, 95 %C.I. 1.01-1.07 p = 0.04) levels outside of flares. CONCLUSIONS:VEXAS patients exhibit a significantly increased risk of both hematologic and non-hematologic malignancies compared with controls, particularly among those with RP, p.Met41Thr mutation, and persistent systemic inflammation.

OBJECTIVES:Refractory manifestations of Behçet's disease (BD) are commonly treated with TNF-α inhibitors; however, a subset of patients do not respond or are intolerant, prompting the need for alternative therapies. This study aimed to assess the real-life use, efficacy, and safety of non-TNF targeted biologic agents in BD. METHODS:Data were retrieved from the International AutoInflammatory Disease Alliance (AIDA) Network Registry for BD. Patients who received any biologic agent other than TNF-α inhibitors at any point during follow-up were included in the study. Clinical and demographic characteristics, prior treatments, and treatment responses at the 3-, 6- and 12-month follow-ups were collected. RESULTS:In total, 65 patients (36 female/29 male) with a mean age of 45.8 ± 13.3 years were included in the sample population for this study. Anakinra was the most frequently used agent (n = 31), with 34.7% of patients with mucocutaneous, 73.3% with musculoskeletal, and 77.7% with ocular involvement showing a partial or complete response. Canakinumab (n = 11) was effective in mucocutaneous, musculoskeletal and ocular involvement, including in some patients previously unresponsive to anakinra. Tocilizumab (n = 15) showed favourable outcomes in ocular and neurological involvement (a complete response in 5 of 6 patients), while 40% experienced worsening or no response in mucocutaneous manifestations. Secukinumab and ixekizumab were effective in patients with mucocutaneous-articular phenotypes, especially those with axial SpA. Ustekinumab (n = 3) and rituximab (n = 5) also demonstrated clinical improvement in selected refractory cases. No new major safety concerns were reported across the treatment groups. CONCLUSION:Biologics targeting IL-1, IL-6, IL-17 and the IL-12/23 pathways may offer therapeutic alternatives in BD patients unresponsive to TNF-α inhibitors. The treatment efficacy varied across phenotypes, highlighting the need for individualized treatment decisions.

ObjectiveThe primary aim of this study was to assess, in Still’s disease, whether the employment of canakinumab at a strictly on-label dose may increase the likelihood of treatment discontinuation due to study-defined long-term remission (LTR), compared with patients receiving lower doses.MethodsPatients were drawn from the international Autoinflammatory Disease Alliance (AIDA) Network registry dedicated to Still’s disease and stratified based on the starting canakinumab dose: the on-label group received either 300 mg every 4 weeks or 150 mg every 4 weeks (corresponding to 4 mg/kg), while the underdosed group received 150 mg every 4 weeks (corresponding to a dose not exceeding 3.5 mg/kg). Bayesian regression models were implemented to estimate the probability of achieving long-term remission with subsequent canakinumab withdrawal in the two groups, as well as the mean differences in probabilities and posterior probabilities indicating whether the on-label group was superior in achieving the endpoint.ResultsIn total, 131 patients (16.7%) were enrolled, 81 (61.8%) receiving the on-label posology and 50 (38.2%) the underdosed posology. The estimated marginal posterior probability of canakinumab discontinuation due to LTR was 19% (CrI 7.5%–34.6%) in the on-label group and 3.9% (CrI 0.7%–15.2%) in the underdosed group, yielding a mean difference of 15.1% (CrI 1.4%–31.4%) and a posterior probability of 98.4%. This difference remained credible, with posterior probabilities ranging from 97.9% to 99.6%, irrespective of disease course or age at disease onset.ConclusionOn-label canakinumab dosing appears to increase the likelihood of study-defined LTR with subsequent treatment discontinuation, compared with underdosed treatment strategies.

Background: VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an autoinflammatory disorder caused by UBA1 mutation. It manifests with inflammatory symptoms and commonly macrocytic anemia, which in up to 50% of cases meets WHO 2022 criteria for Myelodysplastic Neoplasia. Such anemia is believed to be related both to inflammation and early erythroblast mortality, and has no standard therapy beside transfusions, which cause iron overload and impaired quality of life. Aims: to analyse the efficacy and safety of erythropoiesis stimulating agents (ESAs) in VEXAS patients. Methods: an electronic survey was emailed to centers managing VEXAS patients. All patients with confirmed VEXAS by UBA1 testing who received ESA were included. Cytopenias and MDS were classified as per WHO 2022 and stratified by IPSS-R and IPSS-M. Response was evaluated with IWG 2018 response criteria. UBA1 VAF was determined by digital droplet PCR. Results: 32 male patients affected by VEXAS syndrome received ESAs at 13 canters for symptomatic anemia. At baseline 63% of them were transfusion-dependent (n=13 low transfusion burden; n=7 high transfusion burden); 82% had concomitant MDS, mostly low risk. HI-E to ESAs was achieved in 59%, and correlated with lower endogenous erythropoietin levels [OR 0.985 (95%CI=0.972 – 0.999), p=0.033]. Median duration of response was 13 months. 6 responders (31%) lost response after a median of 14 months. UBA1 VAF remained stable compared to baseline, consistently with the evidence that only clone-targeting therapies as azacitidine or allogeneic hematopoietic cell transplantation impact UBA1 burden. After ESA discontinuation, 53% of patients received clone-suppressing therapies, 18% bDMARDS, 24% supportive therapy. During ESAs treatment, only 4 patients experienced deep vein thrombosis (21%). With a median follow up of 22.8 months, 24 patients were still alive (75%). Of 8 deaths, 7 occurred in patients who either lost or never achieved a response, and were transfusion-dependent at the time of ESAs discontinuation. Summary/Conclusion: This study confirms that ESAs are effective and safe in VEXAS patients. Prospective studies are needed to confirm our retrospective findings and to explore the use of therapies such as Luspatercept, approved for anemia in low-risk MDS, to identify optimal anemia treatment for these patients.

ObjectiveVacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality.MethodsGiven the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS. To address this gap, we formed an international multidisciplinary panel of VEXAS experts.ResultsThrough formalized meetings and a voting process, the group developed consensus clinical guidance considerations for the management of VEXAS. These considerations offer practical advice on several key topics: (1) clinical features of VEXAS, (2) UBA1 screening methods, (3) the diagnosis of myelodysplastic syndromes (MDSs) in patients with VEXAS, and (4) prognosis and management. The aim is to provide expert guidance on which patients to test, how to test for VEXAS, how to approach MDS in the context of VEXAS, and considerations for management.ConclusionThis work marks the first formal international consensus guidance for VEXAS and is intended to be used as a resource for clinicians seeking to understand the disease and its management.

Behçet’s disease (BD) frequently arises with exclusively mucocutaneous involvement, but some patients will develop major organ involvement, including ocular inflammation. This study aims to assess the patients’ demographic and clinical characteristics that may be associated with the development of ocular involvement in patients with BD with exclusively mucocutaneous involvement in the early stages. Patients’ data were collected in the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. A total of 328 patients with BD were enrolled, 36 (11

OBJECTIVES:To assess the lung involvement in patients with Still's disease, an inflammatory disease assessing both children and adults. To exploit possible associated factors for parenchymal lung involvement in these patients. METHODS:A multicentre observational study was arranged assessing consecutive patients with Still's disease characterized by the lung involvement among those included in the AIDA (AutoInflammatory Disease Alliance) Network Still's Disease Registry. Still's disease-lung involvement was defined by the presence of pleuritis, parenchymal features, acute respiratory distress syndrome (ARDS) and/or pulmonary arterial hypertension. RESULTS:In total, 90 patients with Still's disease and lung involvement were assessed (mean age 36.3 ± 17.8 years, 35.6% male sex). Among them, 13.3% of patients were paediatrics. These patients with lung involvement mainly showed pleuritis in 72.2% of cases, parenchymal features in 34.4%, ARDS in 9.5% and pulmonary arterial hypertension in 2.3%. After that we focused on patients characterised by parenchymal lung involvement, which is an emergent issue of clinical concern. These patients with parenchymal lung disease were significantly characterized by sore throat, pericarditis and higher values of systemic score than others. Finally, the administration of both IL-1 or IL-6 inhibitors was not associated with the presence of parenchymal lung involvement. CONCLUSION:The clinical characteristics of patients with Still's disease and lung involvement were described in the AIDA network. We also provided a clinical profile of patients with parenchymal lung involvement considering its prognostic relevance. Although providing a clinical landscape of these patients, further studies are needed to fully clarify this issue.

BackgroundVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory condition resulting in severe, often treatment-refractory inflammation. Currently, there are no established treatment guidelines for VEXAS syndrome.ObjectivesTo assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) in a cohort of VEXAS patients.MethodsData from VEXAS patients were obtained from the International AIDA Network VEXAS registry.ResultsData from 36 VEXAS patients were evaluated, with 28 (77.8%) treated with cDMARDs as monotherapy - and concomitant glucocorticoids (GC) - and 8 (22.2%) receiving a combination of different cDMARDs plus GC. Complete response (CR), partial response (PR), and failure to cDMARDs monotherapy were reported in 4/22 (18.2%), 11/22 (50%), and 7/22 (31.8%) courses, respectively. All patients were treated with GCs at the start of cDMARD monotherapy, and no GC discontinuation was observed later. No significant differences were observed in the GC dosage from the start of cDMARDs to the 3-month (p = 0.43), 6-month (p = 0.31), and 12-month (p = 0.21) visits. Conversely, the GC sparing resulted to be statistically significant when using methotrexate (p = 0.02). As for cDMARDs combinations, no cases achieved CR, while PR was observed in 5/9 (55.6%). Seventeen adverse events were reported, seven of which led to discontinuation.ConclusionMany VEXAS patients report a partial benefit from cDMARDs, while a smaller yet not negligible number of patients exhibit a CR; cDMARDs remain a viable option for this disorder, especially when the initial GC dosage is low and the need for a steroid-sparing effect is not immediately urgent.