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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: Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA., Methods: We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score)., Results: A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p = 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36-15.1, p = 0.014), age (per 10-year increase OR 1.05, 1.02-1.68, p = 0.007), and BMI (OR 0.77, 0.63-0.9, p = 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p = 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8-25.3, p = 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement., Conclusions: Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are less prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement., Study Registration: Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010)., (© 2021. The Author(s).)

Objectives: We aimed to evaluate trends of rheumatoid arthritis (RA) mortality reported as the underlying cause of death (UCD) and as multiple causes of death (MCD) in Italy between 2003 and 2015., Methods: Analyses were carried out on the Italian National Cause of Death Register, managed by the Italian National Institute of Statistics (ISTAT). Deaths from January 1, 2003 to December 31, 2015 with any mention of RA were included. Diseases are coded according to the International Classification of Diseases, 10th Edition (ICD- 10, 2009 version). Time trends of age-standardised rates were analysed for RA both as UCD and MCD, and the annual percent change (APC) was estimated., Results: Overall, 26,564 deaths with a mention of RA were retrieved out of 7,595,214 deaths (0.35% of all certificates). The mention of RA as MCD increased throughout the study period, meanwhile the selection as the UCD decreased. RA mortality rates based on the UCD declined (males APC -3.1%, CI -3.9, -2.3; females APC -3.3%, CI -4.1, -2.4); while rates based on the MCD were stable. Specifically, rates were stable or declined among younger subjects and increased in subjects aged ≥80 years., Conclusions: RA was found to be increasingly reported in death certificates in the last two decades in Italy, although it is less frequently reported as the UCD. Due to the increased survival of patients, we observed a shift of RA-related mortality towards the elderly, making RA a comorbidity contributing to death in these patients.