Short-term effectiveness of guselkumab in psoriatic arthritis patients and suggestive features of axial involvement: results from a real-life multicentre cohort.

OBJECTIVE: To evaluate the short-term effectiveness of guselkumab in patients with psoriatic arthritis (PsA) and suggestive features of axial involvement in a prospective "real-life" multicentre cohort. METHODS: Between June 2022 and June 2023, PsA patients with axial involvement were evaluated if treated at least for 4 months with guselkumab. The effectiveness was evaluated by BASDAI, ASDAS, DAPSA, and achievement of BASDAI ≤ 4, also exploiting predictive factors. In a group of patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. RESULTS: Sixty-seven patients with PsA and suggestive features of axial involvement (age 53.4 ± 11.2 years, male sex 26.9%) were treated with guselkumab. After 4 months, a significant reduction of BASDAI, ASDAS, and DAPSA was observed. A ΔBASDAI of -2.11 ± 0.43 was estimated assessing the mean difference values before and after guselkumab administration and 52.2% of patients reached a BASDAI ≤ 4. In 27 patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. A reduction of 0.80 or larger of the sacroiliac joint lesion score was observed in the majority of patients (70.3%) based on MRI improvements, paralleling with the clinical response.No life-threatening side effects were recorded; 17.9% of patients reported minor adverse events mainly injection site reactions. CONCLUSIONS: The short-term effectiveness of guselkumab in patients with PsA and suggestive features of axial involvement was shown. Although further studies are needed, our multicentre "real-life" study may suggest the clinical usability of guselkumab in this context.

The Systemic Score May Identify Life-Threatening Evolution in Still Disease: Data from the GIRRCS AOSD-Study Group and the AIDA Network Still Disease Registry.

OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

The Evaluation of Effectiveness and Safety of Guselkumab in Patients with Psoriatic Arthritis in a Prospective Multicentre "Real-Life" Cohort Study.

INTRODUCTION: Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. METHODS: Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. RESULTS: A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (ß - 15.47, p = 0.001, 95% CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. CONCLUSION: The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.

Systematic Review and Metaanalysis of Pharmacological Interventions in Adult-Onset Still Disease and the Role of Biologic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD). METHODS: Six databases, 2 trial registries, and conference abstracts were searched from January 2012 to February 2023 for studies of pharmacological interventions in people with AOSD. Outcomes were rates of remission and response, discontinuation of concurrent treatments, complications of AOSD, and treatment-related adverse events. Risk of bias was assessed with the Cochrane risk of bias tool and the Joanna Briggs Institute tool for case series. RESULTS: Forty-four studies evaluated treatments, including nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids (CS), conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs (bDMARDs). For bDMARDs, tocilizumab (TCZ), anakinra (ANK), and canakinumab (CNK) had the most available data. Although 3 randomized controlled trials did not show statistically significant benefits of bDMARDs, metaanalyses showed high rates of complete remission and CS discontinuation. Complete remission was 80% (95% CI 59-92%, I 2 36%), 73% (95% CI 58-84%, I 2 66%), and 77% (95% CI 29-97%, I 2 82%) and CS discontinuation was 57% (95% CI 29-81%, I 2 66%), 47% (95% CI 18-78%, I 2 79%), and 34% (95% CI 6-81%, I 2 59%), respectively, for TCZ, ANK, and CNK. Studies with a higher proportion of patients previously treated with bDMARDs showed a trend toward lower rates of CS discontinuation (P = 0.05). The analyses had high clinical heterogeneity, largely because treatments were prescribed as different lines of therapy. CONCLUSION: Evidence supports TCZ, ANK, and CNK therapy for AOSD. However, the magnitude of effect and comparative effectiveness of treatments is uncertain.

Idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH): Similarities, differences and the role of autoimmunity.

Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study.

BACKGROUND: A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The ß-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D. METHODS: The primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters. RESULTS: Forty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (ß = - 1.1, p = 0.019, 95%CI - 1.5 to - 0.76). Also, HOMA2-ß enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, a trend in glycated haemoglobin reduction was also recorded. The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded. CONCLUSIONS: The administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a "bidirectional" benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.

The latest advances in the use of biological DMARDs to treat Still's disease.

INTRODUCTION: Currently, the therapeutic management of Still's disease, a multisystemic inflammatory rare disorder, is directed to target the inflammatory symptoms and signs of patients. The treatment varies from glucocorticoids to disease-modifying antirheumatic drugs (DMARDs), both conventional synthetic and biological (bDMARDs). Usually, in refractory patients, bDMARDs are administered. AREAS COVERED: Among bDMARDs, IL-1 and IL-6 inhibitors are frequently used, as data reported from both clinical trials and 'real-life' experiences. Recently, innovative therapeutic strategies have suggested an early administration of bDMARDs to increase the rate of clinical response and drug-free remission. Some new targets have been also proposed targeting IL-18, IFN-γ, and JAK/STAT pathway, which could be applied to Still's disease and its life-threatening evolution. EXPERT OPINION: Many lines of evidence improved the knowledge about the therapeutic management of Still's disease with bDMARDs. However, many unmet needs may be still highlighted which could provide the basis to arrange further specific research in increasing the rate of clinical response. In fact, Still's disease remains a highly heterogeneous disease suggesting possible diverse underlying pathogenic mechanisms, at least partially, and consequent different therapeutic strategies. A better patient stratification may help in arranging specific studies to improve the long-term outcome of Still's disease.

Recent advances and evolving concepts in Still's disease.

Still's disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still's disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis. Genetic insights into Still's disease involve both HLA and non-HLA susceptibility genes, suggesting the involvement of adaptive immune cell-mediated immunity. At the same time, phenotypic evidence indicates the involvement of autoinflammatory processes. Evidence also implicates the type I interferon signature, mechanistic target of rapamycin complex 1 signalling and ferritin in the pathogenesis of Still's disease and MAS. Pathological entities associated with Still's disease include lung disease that could be associated with biologic DMARDs and with the occurrence of MAS. Historically, monophasic, recurrent and persistent Still's disease courses were recognized. Newer proposals of alternative Still's disease clusters could enable better dissection of clinical heterogeneity on the basis of immune cell profiles that could represent diverse endotypes or phases of disease activity. Therapeutically, data on IL-1 and IL-6 antagonism and Janus kinase inhibition suggest the importance of early administration in Still's disease. Furthermore, there is evidence that patients who develop MAS can be treated with IFNγ antagonism. Despite these developments, unmet needs remain that can form the basis for the design of future studies leading to improvement of disease management.

The assessment of the drug retention rate of secukinumab in patients with psoriatic arthritis in a real-life multicentre cohort.

OBJECTIVES: We aimed to evaluate the drug retention rate (DRR) of secukinumab, an anti-IL-17A monoclonal antibody, in patients with psoriatic arthritis (PsA) in a real-life cohort, and to assess the impact of comorbidities and patient clinical characteristics on the DRR of secukinumab. METHODS: A retrospective study of prospective followed-up patients was performed to evaluate the DRR of secukinumab on patients with PsA attending the recruiting centres between January 2016 and June 2022. RESULTS: In 207 patients with PsA, a 60-month DRR of secukinumab of 57.0% was estimated (mean time of administration of 21.5±17.1 months). Male gender, age ≥65 years, disease duration ≥5 years and ≥10 years did not influence the DRR of secukinumab. The presence of comorbidities, considering any concomitant disorder, did not affect the DRR of secukinumab. In patients with cardiometabolic multimorbidity, a trend toward a better DRR of secukinumab was recorded. In fact, patients with high blood pressure, dyslipidaemia, and type 2 diabetes showed a trend toward an improved DRR of secukinumab. Furthermore, the presence of obesity did not influence the DRR of secukinumab. Different dosages, previous bDMARDs, and concomitant therapy with csDMARDs did not influence the DRR of secukinumab. CONCLUSIONS: A cumulative 60-month DRR of secukinumab of 57.0% in patients with PsA was retrieved. The presence of cardiometabolic multimorbidity could be associated with an improved DRR of secukinumab, whereas obesity did not affect this feature in our cohort. Previous bDMARDs, concomitant csDMARDs, and different drug dosages could not influence the DRR of secukinumab over time.

Association between Patient Acceptable Symptom State and disease activity in psoriatic arthritis is disrupted by confounders, including comorbid fibromyalgia.

OBJECTIVES: Due to the prevalence of fibromyalgia in psoriatic arthritis (PsA) patients, any evaluation about PsA-specific patient-reported outcomes (PROs) should take in account the possible bias related to this comorbidity. Patient acceptable symptom state (PASS) is a patient-reported measure evaluating the acceptable and/or satisfactory level of symptoms in rheumatic diseases, which has been proposed as a disease activity index, in patients with PsA. Thus, this study was designed to analyse if the association between PASS and PsA disease activity may be biased by the presence of comorbid fibromyalgia. METHODS: A multi-centre, cross-sectional, observational study enrolling consecutive PsA participants has been conducted from July 2021 to November 2021. The Disease Activity for Psoriatic Arthritis (DAPSA) was collected; the following formulation of PASS question: 'Think about all the ways your PsA has affected you during the last 48 hours. If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable to you?', was submitted to our participants. RESULTS: Multivariable logistic regressions, adjusted for the presence of fibromyalgia, did not show any significant association between PASS and DAPSA low disease activity, DAPSA as nominal variable (remission, low disease activity, moderate disease activity, high disease activity) and DAPSA as continuous variable. CONCLUSIONS: Our data suggest that fibromyalgia influences the patient's perception of the disease and has a negative impact on PASS status independently of disease activity, thus limiting the utility of this Patient reported outcome in real world clinical practice.

Still's disease continuum from childhood to elderly: data from the international AIDA Network Still's disease registry.

OBJECTIVE: Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease. METHODS: Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease. RESULTS: A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. CONCLUSIONS: Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease.

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment. Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent. Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment. Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment.

Derivation and validation of four patient clusters in Still's disease, results from GIRRCS AOSD-study group and AIDA Network Still Disease Registry.

BACKGROUND: Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients. METHODS: Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters. RESULTS: K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients. CONCLUSIONS: Four patient clusters in Still's disease may be recognised by a multidimensional characterisation ('Juvenile/Transitional', 'Uncomplicated', 'Hyperferritinemic' and 'Catastrophic'). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.

The assessment of atlantoaxial joint involvement in patients with rheumatoid arthritis, results from an observational "real-life" study.

Atlantoaxial joint is a possible affected site during rheumatoid arthritis (RA) and, in this work, we evaluated its occurrence and associated characteristics in a "real-life" cohort. By a medical records review study of RA patients longitudinally followed-up, the occurrence of severe atlantoaxial joint involvement was estimated (incidence proportion and incidence rate per 1000 person-years at risk). Regression analyses were also exploited to evaluate possible associated factors. Based on these findings, a prospective recruitment was performed to build a descriptive cross-sectional study in evaluating a subclinical atlantoaxial joint involvement in patients with the same clinical characteristics. Retrospectively, 717 patients (female 56.6%, age 64.7 ± 12.3 years) were studied. The incidence proportion of severe atlantoaxial joint involvement was 2.1% [1.5-2.5], occurring in 15 out of 717 patients, and identified by both MRI and CT scan. Considering over 3091 person-years, an incidence rate of 5.2 × 1000 [2.9-8.3] person-years was estimated. Regression analyses suggested that male gender, a longer disease duration, ACPA positivity and extra-articular manifestations resulted to be significantly associated with a severe atlantoaxial joint involvement. Given these findings, 30 asymptomatic patients were selected according to these clinical characteristics and underwent MRI of cervical spine. To date, almost 50% of these asymptomatic patients showed a subclinical atlantoaxial joint involvement. The occurrence of the severe atlantoaxial joint involvement in RA patients was estimated in a "real-life" setting. Male gender, ACPA positivity, long disease duration, and extra-articular manifestations could be associated with the severe atlantoaxial joint involvement in RA. MRI could provide a useful clinical tool to early evaluate the atlantoaxial joint involvement in RA, also in asymptomatic patients.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.

Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase.

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001). Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population.

Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry.

To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data.

Burden of adult-onset Still's disease: A systematic review of health-related quality of life, utilities, costs and resource use.

Adult-onset Still's disease (AOSD) poses a not well estimated burden on patients and healthcare systems. To assess this burden, a systematic review (SR) was undertaken to identify health-related quality of life (HRQoL), utilities, costs and healthcare resource use data. Searches of twelve databases, four conferences, and three key technology assessment and regulatory agency websites were conducted in August 2022. Reference lists of retrieved SRs published since 2017 were also checked. Overall, 16 studies were eligible for inclusion. Eight studies reported HRQoL outcomes, one of which also reported utilities data. Two studies reported direct costs outcomes, and seven reported healthcare resource use data. No indirect costs were identified. A range of outcomes were reported, thus limiting the comparability of results across studies. SF-36 data were impaired in AOSD on most scales, especially those concerning physical activity. Mean SF-36 data were lower across all subscales in patients with active AOSD compared with inactive AOSD. Biologic therapy showed improvements in the SF-36 physical health summary. Utility scores (one study) were significantly lower for AOSD than for healthy controls. Limited direct economic costs data were identified but were substantial where reported. Hospital length of stay ranged from 6.1 to 23.5 days. The SR showed there is a paucity of research reporting the HRQoL and cost burden of AOSD.