Elena Bravi

Background/Objectives: Systemic sclerosis (SSc) patients frequently develop osteoporosis; however, vertebral fracture risk factors remain poorly characterized. This study identifies general and SSc-specific predictors of vertebral fractures in SSc patients undergoing osteoporosis evaluation. Methods: This multicenter cross-sectional study enrolled consecutive SSc patients meeting ACR/EULAR 2013 criteria with suspected osteoporosis. Data included demographics, disease characteristics, bone density (DXA), and vertebral imaging. Stepwise logistic regression analyzed fracture associations (p ≤ 0.05 significant). Results: The majority of 103 enrolled patients were female and all were post-menopausal. The prevalence of osteoporosis was 52.4%, that of vertebral fractures was 38.8%, and that of osteopenia was 28.1%. General risk factor analysis identified family history of fragility fractures (OR 11.8, p = 0.008) and vertebral T-scores (OR 0.6, p = 0.049) as significant predictors. When adding SSc-specific factors, only family history (OR 13.8, p = 0.03) and gastrointestinal (GI) involvement (OR 4.8, p = 0.05) remained significant. Conclusions: Vertebral fractures in SSc patients are strongly linked to a family history of fractures. The suggestive association with GI involvement may imply a significant role for malabsorption-related metabolic impairment. Prioritizing bone density screening in SSc patients with GI symptoms may enable earlier intervention and reduce fracture risk.

Background and Objectives: The treatment landscape for Rheumatoid Arthritis (RA) has evolved significantly with the introduction of Janus kinase inhibitors (JAKi), such as Tofacitinib (TOFA), which offer a new therapeutic option for patients who have failed or are intolerant to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Safety concerns, particularly related to cardiovascular and cancer risks, prompted a need for additional investigation in real-world clinical settings. This study aimed to evaluate the long-term effectiveness and predictors of response to TOFA in two subpopulations of RA patients, categorized by differing cardiovascular risk profiles. Materials and Methods: This was a retrospective, multicenter observational study conducted as part of the BIRRA project, involving 23 Italian rheumatological referral centers. A total of 213 patients diagnosed with RA and treated with TOFA were included, with data collected on baseline demographics, clinical history, disease activity, and comorbidities. Patients were divided into high-risk and low-risk cardiovascular groups based on age (≥65 years) and the presence of at least one cardiovascular risk factor. Disease activity was assessed at baseline, 6 months, and 12 months using DAS28-ESR and DAS28-CRP. Treatment response was evaluated using intention-to-treat (ITT) and per-protocol (PP) approaches. Predictors of low disease activity (LDA) and remission were assessed through logistic regression, and clustering analyses were used to identify subgroups of patients with different therapeutic responses. Results: The study included 213 patients, with 129 classified as high-risk. For the overall cohort, patients achieving LDA and remission at 6 months were 20% and 12%, respectively, for the ITT analysis, and 29% and 14% for the PP analysis. At 12 months, 26% of patients reached LDA, and 17% achieved remission according to ITT, while for the PP analysis, these rates were 30% and 19%, respectively. No significant differences in remission or LDA rates were observed between the high-risk and low-risk groups. In the high-risk subgroup, 17% of patients reached LDA and 9% achieved remission at 6 months (ITT analysis), while these rates increased to 22% and 13%, respectively, in the PP analysis. At 12 months, 22% achieved LDA and 13% achieved remission in the ITT analysis, while 28% and 17% did so in the PP analysis. The reduction in DAS28-ESR and DAS28-CRP scores was significant (p < 0.001) across all time points for both high-risk and low-risk patients. Logistic regression analyses revealed that none of the baseline characteristics—including age, sex, comorbidities, rheumatoid factor, anti-citrullinated protein antibody (ACPA) positivity, initial disease severity, or treatment history—were significant predictors of remission or LDA at 6 or 12 months. The clustering analysis suggested that older patients, particularly those with worse baseline DAS28 scores, tended to show a less favorable response to treatment, potentially indicating impacts of age-related factors such as immunosenescence on therapeutic outcomes. Conclusions: Tofacitinib demonstrated similar effectiveness in both high- and low-risk cardiovascular subgroups of RA patients, with significant reductions in disease activity observed at both 6 and 12 months. Despite safety concerns related to cardiovascular risk, TOFA remained an effective treatment option across patient subgroups, with no significant differences in remission or LDA rates based on cardiovascular risk profiles. Age appeared to negatively impact treatment response, highlighting the role of immunosenescence in RA management. These findings support the use of TOFA as a personalized therapeutic option for RA, emphasizing the need for careful evaluation of cardiovascular and age-related risks in clinical decision-making.

Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA’s first safety alert (1 July–31 October 2019, Group 1), between the first and second alerts (1 November 2019–29 February 2020, Group 2), or between the second and third alerts (1 March 2021–30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Introduction: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. Objective: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. Methods: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann–Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. Results: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1–2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1–3)) and T2 (median LEI 0 (IQR 1–2)). Conclusion: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.