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Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

Objective: Dose reduction of biologic drugs in patients with psoriatic arthritis (PsA) who are in Minimal Disease Activity (MDA) is now considered a feasible option. This study evaluated which baseline clinical and ultrasonographic (US) factors may be predictive of disease activity after anti-TNF-α spacing., Methods: This observational, prospective, multicentre, 12-month study enrolled consecutive adult patients with PsA taking TNF-α inhibitors and in stable MDA who accepted to reduce their dose therapy by doubling the administration interval. Data collection included demographics, personal history, clinical disease characteristics, and joints and entheses US features. Patients maintaining the MDA were compared with those who experienced a disease flare during the 12 months of follow-up. The statistical analysis included the comparison between groups and the search of the factors associated with persistence of MDA., Results: Of the evaluable 72 patients (29 females and 43 males), 55 (76.4%) maintained a state of MDA while 17 (23.6%) experienced a disease relapse. Baseline values of DAPSA <2 and of BASDAI <1.5, and lower BASDAI and DAS28 values were significantly associated with maintenance of MDA. The multivariate analysis showed that baseline values of DAPSA <2 and of BASDAI <1.5 were predictive of persistence of MDA. Baseline US findings were not associated with the outcome of disease activity., Conclusions: In this study, anti-TNF-α spacing proved to be feasible in most of the PsA patients in a stable MDA. The only factor predictive of persistence of remission was a very low clinical disease activity at baseline., (Copyright © 2025. Published by Elsevier Masson SAS.)

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: Upadacitinib (UPA) is a selective, reversible Janus kinase inhibitor (JAKi) approved for the treatment of RA. However, there is still no solid evidence on the long-term efficacy of UPA in treated patients. The purpose of this study was to determine the efficacy of UPA to obtain remission or low disease activity (LDA) in a series of UPA patients in patients with RA after 6 and 12 months of treatment in a real-world setting., Methods: A series of 111 consecutive patients treated with UPA in 23 rheumatology centers were enrolled. Personal history, treatment history and disease activity at baseline, after 6 and 12 months were recorded. Intention-to-treat (ITT) and per-protocol (PP) analyses assessed achievement of remission or LDA or defined as DAS28 <2.6 and ≤3.2, respectively. Logistic regression analysis examined the role of several independent factors on the reduction of disease activity after 6 months of treatment., Results: Of the initial group of 111 subjects at baseline, 86 and 29 participants completed clinical assessments at 6 and 12 months. According to ITT analysis, the rates of remission and LDA were 18% and 18% at 6 months and 31.5% and 12.5% at 12 months, respectively. PP analysis showed higher rates of remission and LDA at 6 (23.3% and 19.8%) and 12 months (55.2% and 20.7%). Results of multivariate logistic regression analysis indicated that a low DAS28 score (P=0.045) was the only predictor of achieving remission at 6 months. None of the baseline factors predicted remission/LDA at 6 months., Conclusions: RA patients treated with UPA achieved a significant rate of disease remission or LDA in a real-world setting. The 6-month response was found to depend only on the baseline value of DAS28, while it was not influenced by other factors such as disease duration, line of treatment or concomitant therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids.

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.

Background: In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA., Methods: In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18-6 and 13-5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests., Results: The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6-65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively., Conclusions: PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Macchioni, Marchesoni, Ciancio, Sandri, Zabotti, Vukatana, Montaguti, Focherini, Govoni, Spinella, Malavolta, Zuliani, Bruschi, Mascella and Salvarani.)

We present tocilizumab desensitization of a 47-year-old woman affected by rheumatoid arthritis with full body delayed erythematous urticarial reaction. Skin test for tocilizumab gave cutaneous reaction after 6 h at 20 mg/mL. The schedule of desensitization was then adapted for non-immediate reaction. We prepared a desensitization procedure reaching the cumulative dose of 516 mg in 5 weeks. After 6 months, the repetition of skin tests had a negative result, with demonstration of tolerance induction. Today the patient has good control of the disease., (© 2018 S. Karger AG, Basel.)

Objectives: To perform a systematic review aimed to identify studies addressing the effect of the establishment of a structured organisation programme, named early arthritis clinic (EAC), finalized to manage patients with early arthritis (EA) or suspected early rheumatoid arthritis (ERA)., Methods: A literature search was performed until May 2012 using electronic databases. Additional information was obtained through a hand and grey literature search. Primary and secondary outcomes and eligibility criteria have been defined., Results: The search provided a total of 3367 citations and, after the selection process, 11 non randomised controlled trials were selected, including a total of 8240 participants. The efficacy of EAC did clearly emerge with regard to reduction of the referral lag time and of the time to treatment (secondary outcomes). Only two studies met the primary outcomes: one study demonstrated that the EAC contributed to reducing disease activity and radiographic progression but not functional disability, while another reported a reduction of pain after a 6-12-month period of follow-up., Conclusions: Whether the establishment of EAC would improve the prognosis of EA in terms of primary outcomes such as clinical, functional and radiologic progression compared to patients managed outside from EAC does appear a still poorly addressed issue in the literature, which should be recognised as an urgent unmet need by the rheumatology community to gain more evidence-based information on this topic.

Cluster randomization, where groups (or clusters) of subjects, rather than single individuals, are randomly allocated to intervention groups, is increasingly being adopted in studies to evaluate interventions directed at a whole area or healthcare unit (such as a hospital ward, or a medical practice). Studies that use this method of randomization are referred to as cluster randomized trials (CRT) and have considerable organizational and economic advantages. However, CRTs have distinctive ethical issues that need to be considered and most importantly, require a series of methodological modifications during data analysis and calculation of sample size (during which additional parameters, such as the intracluster correlation coefficient and the design effect, need to be obtained). Methodological guidelines for conducting CRTs have been published in November 2002. However, no scientific articles dealing with the methodology associated with the design and analysis of this type of study have yet been published in Italian. The aim of this article, therefore, is to provide methodological support to healthcare researchers who are planning a CRT, through a description of the methodology used in the Raffaello project. This project is in the start-off phase in the Marche and Abruzzo regions of Italy and represents an excellent case study, it being a CRT aimed at evaluating the efficacy of a Disease Management model in the general population (with general practitioners therefore, being the cluster of randomization).