Objective To evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet’s phenotype resistant to conventional and biologic treatment. Methods A multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet’s syndrome fulfilling the International Criteria for Behçet’s Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations. Results At 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage. Conclusions Our study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet’s syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.

Accelerated atherosclerosis is one of the major causes of morbidity in patients with systemic lupus erythematosus (SLE). Endothelial dysfunction (ED) is considered an early marker of atherosclerosis. It is a reversible alteration, thus representing an attractive target for prevention strategies against cardiovascular disease. Studies have shown that ED occurs in patients with SLE even in the absence of severe, active disease. Hydroxychloroquine (HCQ) is widely used in SLE to control disease activity, but its use is also associated with an improvement in long-term prognosis. Beyond the beneficial effect in well-established disease, our hypothesis is that treatment with HCQ might have a beneficial impact on ED prevention in SLE. The aim of this study was to assess the impact of early treatment with HCQ on ED in a murine model of SLE. Twelve-week-old NZB/W F1 (NZ) and C57BL/6 J mice (controls) were allocated to receive HCQ or vehicle for 6, 12, or 18 weeks. Proteinuria and anti–double-stranded DNA autoantibodies were determined. ED was assessed in mesenteric arteries (pressurized myography). Nitric oxide (NO) availability and reactive oxygen species (ROS) production were evaluated. Vascular ROS production was measured with dihydroethidium (DHE) fluorescent dye. Starting from 18 weeks of age, NZ mice showed a progressive reduction in NO availability, which was normalized by ascorbic acid and apocynin in the up to 24-week-old group, and partly ameliorated in older animals. HCQ administration normalized the NO availability in the up to 24-week-old group, with a partial amelioration in the 30-week-old group. DHE analysis revealed a progressive increment of vascular ROS generation among NZ groups, which was prevented by apocynin. Similarly, in the NZ HCQ-treated group, vascular ROS production was abrogated. The ED that characterizes this mouse model of SLE is caused by the nicotinamide adenine dinucleotide phosphate oxidase–driven ROS excess. Very early treatment with HCQ is able to exert vascular protection via an antioxidant effect.

This study aims to update the European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of Behçet's syndrome according to the updated EULAR standard operating procedures. The task force comprised 29 members from 11 countries, including 19 rheumatologists, 2 ophthalmologists, 1 dermatologist, 1 gastroenterologist, 1 neurologist, 1 health professional, 2 patient research partners, and 2 Emerging EUlar NETwork members. Research questions were proposed by the task force through a Delphi survey and formulated into patients, interventions, comparison, and outcomes (PICO) questions for the systematic literature review. The results of the systematic literature review were discussed among the task force members. Previous recommendations and overarching principles were modified, and new recommendations were developed as needed. The updated recommendations were voted, and the levels of evidence and levels of agreement were determined. The updated recommendations consist of 5 overarching principles and 12 recommendations that were tabulated according to organ involvement. Among the 12 recommendations, 1 was a new recommendation, 7 recommendations were modified, and only the wording was changed in 4 recommendations. The overarching principles focus on the importance of recognising the relapsing and remitting disease course and individualising treatment according to disease activity and prognostic risk factors, and emphasise the importance of a multidisciplinary approach, patient education, and shared decision making for optimal care. For mucocutaneous and joint involvement, colchicine is recommended as the first-line treatment modality. Apremilast and immunosuppressives such as tumour necrosis factor alpha (TNFα) inhibitors are recommended for refractory patients. For patients with organ involvement, more aggressive treatment with glucocorticoids and immunosuppressives is recommended for rapid induction of remission. Early use of monoclonal antibodies against TNFα is encouraged in patients with organ or life-threatening manifestations. These recommendations, which were updated based on new evidence and expert opinion, provide guidance for all stakeholders involved in the management of patients with Behçet's syndrome to improve the quality of care of these patients.

Background and Objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and Methods: This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (p = 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (p = 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p = 0.009), which persisted even after adjustment for pathology (p = 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 [confidence interval (CI) 1.750–5.242], p < 0.0001} and those previously treated with other biologic agents [HR = 1.818 (CI 1.007–3.282), p = 0.047] were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p < 0.0001). Significant corticosteroid-sparing (p = 0.033) and cDMARD-sparing effects (p < 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient’s safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.