Baricitinib retention rate: 'real-life' data from a mono-centric cohort of patients affected by rheumatoid arthritis.

Objectives: The aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection. Materials and methods: Patients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort's demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks. Results: Ninety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p < 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation. Conclusion: Our data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects.

Effects of antiresorptive agents on body composition: a case-control retrospective study.

Introduction: Osteoporosis is the most represented metabolic bone disease and is characterized by the reduction of bone mineral density (BMD), exposing patients to high fracture risk and disability. Bisphosphonates (BPs) are the main compounds exploited in treatment of osteoporosis and significantly reduce fracture risk. Sarcopenia is the pathological reduction of muscle masses and strength, and many studies highlighted its co-existence in patients with impaired bone mass. Indeed, the pathological reduction of lean tissue has been linked to a higher risk of falls and, consequently, fractures and disability. Moreover, the pathological reduction of lean tissue seems to share many pathological mechanisms with impaired bone strength and structure; thus, in this context, we decided to conduct a retrospective case-control study aimed at evaluating the effects of BPs on lean mass and body composition. Material and methods: We enrolled postmenopausal women from our metabolic bone diseases outpatient clinic who underwent at least two consecutive dual-energy X-ray absorptiometry (DXA) examinations concomitantly to the beginning of an antiresorptive agent. The body composition of patients and controls was compared by fat masses, lean masses and android-to-gynoid ratio (A/G ratio). Results: A total of 64 female subjects were considered for the study: 41 starting a BPs and 23 without treatment were used as control. The fat masses and lean masses appeared to be unaffected by BPs. Conversely, A/G ratio was lower in BPs group after 18 months of therapy compared to baseline (p < 0.05). From the stratification based on the single BP we failed to highlight any significant difference between the tested variables. Conclusions: Bisphosphonates treatment did not modify lean tissues, however a significant reduction of A/G ratio in BP group was documented. Thus the BPs seems to act on patients body composition and extra-skeletal tissues but larger prospective studies are needed to evaluate whether these modifications have clinical relevance.

Peripheral Macrovascular Involvement in Systemic Sclerosis: A Cohort Study by Color and Spectral Doppler Ultrasonography.

OBJECTIVES: Systemic sclerosis (SSc) is a disease characterized by diffuse sclerosis of skin and organs and small vessel vasculopathy. Despite it, large vessels can also be involved with ulnar artery vasculopathy, revealing as a more frequent feature of SSc. The aim of this paper is to assess the macrovascular involvement of SSc patients through an ultrasound (US) evaluation of radial and ulnar arteries. METHODS: Radial and ulnar resistance indices (RIs) and peak systolic velocity (PV) (cm/s) together with clinical features of SSc patients were evaluated. Raynaud phenomenon (RP) and healthy control (HC) groups were used for comparison. RESULTS: Forty-three SSc patients were evaluated. Twelve patients (28%) had ulnar artery occlusions (UAOs). In nine cases (75%), UAOs were bilateral. A high UAO prevalence (42%) was found in SSc patients with late nailfold-video-capillaroscopy (NVC) pattern (p = 0.0264). Patients with UAOs had digital ulcers (DUs) in 10 cases (83.3%). Radial and ulnar PVs were lower in SSc and RP patients than the HC group. Radial and ulnar RIs were higher in SSc and RP patients than the HC group. A decision tree analysis led to the classification of 70% of SSc patients with an ulnar RI > 0.82 and ulnar PV > 2.8 cm/s. The most influential variables on UAO development were interstitial lung disease (ILD) (p = 0.002) and NVC pattern (p = 0.002). A positive correlation was shown between modified Rodnan skin score (mRSS) and ILD (p = 0.283; r = 0.033), mRSS and DU (r = 0.344; p = 0.012) and DU and ILD (r = 0.303; p = 0.024). Male sex was associated with increased UAO frequency (p = 0.042). CONCLUSIONS: UAO is a peculiar feature of severe SSc present in 28% of the cases, particularly associated with the presence of ILD and late NVC pattern. In 75% of the cases, UAOs are bilateral. DUs are very frequent in patients with UAOs (83%). The RI evaluated by US could be useful to distinguish SSc from HC patients. US could be a useful tool for assessing high-risk DU development in patients.

Comparing biologic options for the management of Behcet's disease-related uveitis.

INTRODUCTION: Behçet's disease (BD) associated uveitis occurs in approximately 50-70% of the patients. Ocular involvement in BD may induce a severe affection of visual function, leading to a considerable decrease in patients' quality of life. The risk for severe visual loss increases when the ocular posterior segment is involved and in patients with no adequate treatment. AREAS COVERED: Monoclonal tumor necrosis factor (TNF) biotechnological inhibitors represent a relatively recent milestone for the treatment of non-infectious uveitis (NIU) also in BD patients. In addition to TNF inhibitors, further biologic agents have been increasingly proposed for multi-recalcitrant cases, as for interleukin (IL)-1 and IL-6 inhibitors. However, evidence on these new opportunities requires to be widened in the next future. EXPERT OPINION: Joining the forces for scientific efforts is essential to quickly obtain solid acquisitions useful for the everyday clinical practice. To this end, the Auto-Inflammatory Disease Alliance (AIDA) Network has recently supported the development of an international registry dedicated to NIU and other inflammatory ocular involvement observed in BD patients. This will be essential to resolve current and future unmet needs burdening the everyday clinical practice.

The diagnostic role of pathergy test in patients with Behçet's disease from the Western Europe.

The aim of the study is to evaluate the frequency and features of positive pathergy test (PPT) in Italy, its role in the diagnosis of Behçet's disease (BD), and any association with other BD-related manifestations. 52 BD patients, 52 patients with axial spondyloarthritis (ax-SpA), and 26 healthy controls (HCs) underwent intradermal injection of normal saline and intradermal needle soaked with fresh self-saliva. The results of pathergy tests were statistically analysed in the light of demographic, clinical, and therapeutic features of subjects enrolled. Pathergy test performed with saline resulted always negative in all groups. Skin prick test using self-saliva resulted in the occurrence of a papule in 3 (5.8%) BD patients and in 1 (1.9%) patient with ax-SpA. A ≥ 15 mm erythematous area surrounding the needle prick site was observed in 22 (42.3%) BD patients, 5 (9.6%) patients with ax-SpA, and 2 (7.7%) HCs (p = 0.00002). The frequency of skin erythema was significantly more frequent in patients with BD than those with ax-SpA (p < 0.0001) and HCs (p = 0.003). No statistically significant differences were observed between ax-SpA patients and HCs (p = 1.000). The occurrence of skin erythema at pathergy test was not associated with any BD-related clinical manifestation. Erythema at self-saliva prick test presented a sensitivity of 42.31% (CI 28.73-56.80%) and a specificity of 91.03% (CI 82.38-96.32%). The development of a ≥ 15 mm erythematous area at self-saliva prick test could be sufficient to unveil the hyper-reactivity of the innate immune system in BD patients from Western Europe, where the development of skin erythema shows good sensitivity and specificity toward the diagnosis of BD.

The Role of Biologic Agents in the Management of Pediatric-Onset Noninfectious Posterior Scleritis.

Registry-based observational prospective study aimed at describing the use of biologic drugs in pediatric-onset scleritis. Data were collected at baseline, at 3-, 6-, 12-month follow-up and at last assessment. Scleral inflammation was graded according to Sen classification. Five patients (9 eyes) treated with adalimumab, infliximab, abatacept and secukinumab were included. All patients were previously treated with conventional immunosuppressors and glucocorticoids. Median biologic treatment duration was 28 (IQR = 118) months. At 6-months, scleritis resolved in all eyes. At 12-months, complete disease control was observed in 7/9 eyes (77.8%). The number of relapses 12 months before and after treatment initiation was 17 and 2, respectively. Mean BCVA was 0.83 (range 0.3-1.0) at baseline and 1.0 for all eyes after 12 months. Glucocorticoids had been withdrawn in 4/5 patients.In conclusion, biological agents proved to be effective in pediatric-onset scleritis, allowing a noticeable steroid-sparing effect and preserving visual function and bulbar integrity.

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases.

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs). Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance. Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients. Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases. NCT05200715 available at https://clinicaltrials.gov/.

Clinical profile and evolution of patients with juvenile-onset Behçet's syndrome over a 25-year period: insights from the AIDA network.

Behçet's syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263-0.932], p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.

Real-Life Data on the Efficacy of Canakinumab in Patients with Adult-Onset Still's Disease.

BACKGROUND: Interleukin-1 inhibition has revealed to be a successful treatment approach for patients with adult-onset Still's disease (AOSD). However, real-life experience is focused on the use of anakinra, while data about canakinumab (CAN) are mainly based on case reports and small case series. Patients and Methods. Patients classified with AOSD according to Yamaguchi criteria and treated with CAN were consecutively enrolled. Their clinical and therapeutic data were retrospectively collected and statistically analysed to assess the role of CAN as a therapeutic opportunity in AOSD patients in terms of clinical and laboratory disease control along with corticosteroid-sparing effect. RESULTS: Nine AOSD patients (8 females and 1 male) treated with CAN for 15.00 ± 12.3 months were enrolled. Resolution of clinical manifestations was reported in 8/9 cases at the 3-month assessment; a significant decrease in the number of tender joints (p = 0.009), swollen joints (p = 0.027), and disease activity score on 28 joints-C-reactive protein (DAS28-CRP) (p = 0.044) was observed during the study period. The systemic score of disease activity significantly decreased at the 3-month and 6-month assessments and at the last visit compared to the start of treatment (p = 0.028, p = 0.028, and p = 0.018, respectively). The daily corticosteroid dosage was significantly reduced at the 3-month and at the last follow-up visits (p = 0.017 and p = 0.018, respectively). None of the patients experienced adverse events or severe adverse events during the follow-up. CONCLUSIONS: CAN has shown prompt and remarkable effectiveness in controlling AOSD activity in a real-life contest, with a significant glucocorticoid-sparing effect and an excellent safety profile.

Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF-α Receptor-Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network.

This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients' data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p < 0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p < 0.01 and p < 0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p < 0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p < 0.01), while oral aphthosis was more frequently found in the LP variant group (p < 0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p < 0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p < 0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p < 0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p < 0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p < 0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p < 0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.