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A response by G. Iannucci, C. Balsano, M. Paroli, E. Scarpellini, G. Leone and M. F. Giannoni to a letter to the editor about their article "Office Normotensives With a Minimal Augmentation of Intima-Media Thickness of Common Carotid Arteries: Really Normotensives," in the 2013 issue is presented.

Objective: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA)., Methods: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA-seq analysis whereas telomere length and dysfunction were measured by RT-PCR and IF-fluorescence in situ hybridization (FISH), respectively., Results: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared to HD and RA patients. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (TNFα), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer (NK) markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response (DDR) activation, telomere shortening and dysfunction., Conclusion: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in SpA patients that represents a possible player in disease pathogenesis., (© 2025 American College of Rheumatology.)

Background: Psoriatic arthritis (PsA) phenotypes show different responses to the many available drugs. For a tailored medicine, it is important to choose the most effective treatment according to patients' characteristics. Apremilast is recommended in PsA with moderate activity. In clinical practice, the most suitable PsA patients for apremilast are those affected by the peripheral oligo-articular arthritis. However, it is not so straightforward to definitely identify this phenotype. Musculoskeletal ultrasound (MUS) is a good tool for detecting the joints actually involved by PsA. The aim of this study is to verify if MUS assessment is useful in selecting the best PsA responders to apremilast., Methods: The following data of all consecutive PsA patients from 15 centres were recorded: anamnestic data, disease activity, PsA phenotype, apremilast treatment duration and reason of suspension. MUS assessment before apremilast treatment was the criteria which clustered patients in two groups. Apremilast retention rate estimate the drug's effectiveness. The Cox analysis revealed the risk factors associated with treatment persistence. Mann-Whitney U and Chi-squared tests assessed the intergroup differences., Results: Only 40% of 356 patients (M:F: 152/204; median age 60 yrs) received MUS examination. In MUS group the moderate disease (median DAPSA 22.9 vs 26.9; p=0.0006) and the oligo-articular phenotype (63.6% vs 36.1%, p<0.0001) were more common. The retention rate was higher in MUS group (HR 0.55 IC95% 0.32-0.94; p=0.03)., Conclusion: In apremilast treated PsA patients, baseline MUS assessment is related to an increased retention rate. MUS may identify patients' characteristics favourable to apremilast response., Competing Interests: A Ariani has received honoraria as a speaker and an advisory board member of Amgen, Bristol-Myers Squibb, Boeringher, Bruno Farmaceutici, Janssen, Lilly, Novartis, Novo Nordisk, Sanofi, and Zentiva. F Lumetti has received honoraria as an advisory board member of Amgen. None of the other authors have any potential conflicts of interest to disclose in relation to this work., (© The Author(s).)

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.

Chronic pain (CP) affects about 30% of the global population and poses significant challenges to individuals and healthcare systems worldwide. The interactions between physiological, psychological, and social factors are crucial in the onset and development of CP conditions. This study aimed to evaluate the effectiveness of mindfulness-based intervention, examining its impact on perceived stress (PSS), depression and anxiety (BDI-II, PGWBI/DEP, SAS, STAI Y), sleep quality (PSQI), and mindfulness abilities (MAAS) in individuals with CP. Participants (N = 89, 84.3% female) underwent one of two diagnoses [fibromyalgia (FM) or low back pain (LBP)] and took part in an MBSR intervention. The mindfulness program proved effective in reducing PSQI scores (F = 11.97; p < 0.01) over time, independently of the type of diagnosis. There was also a marginal increase in trait mindfulness as measured by MAAS (F = 3.25; p = 0.07) in both groups. A significant difference between the two groups was found for the effect on PSS: F (1,87) = 6.46; p < 0.05. Mindfulness practice also reduced anxiety in FM and depressive symptoms in LBP, indicating a reduction in psychological distress among participants. Our findings suggest that mindfulness-based interventions may offer promising avenues for personalized pain management in clinical settings.

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.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an overproduction of pro-inflammatory cytokines. A primary and a secondary form are distinguished depending on whether or not it is associated with hematologic, infectious, or immune-mediated disease. Clinical manifestations include fever, splenomegaly, neurological changes, coagulopathy, hepatic dysfunction, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis. In adults, therapy, although aggressive, is often unsuccessful. We report the case of a 41-year-old man with no apparent history of previous disease and an acute onset characterized by fever, fatigue, and weight loss. The man was from Burkina Faso and had made trips to his home country in the previous five months. On admission, leukopenia, thrombocytopenia, increased creatinine and transaminases, LDH, and CRP with a normal ESR were found. The patient also presented with hypertriglyceridemia and hyperferritinemia. An infectious or autoimmune etiology was ruled out. A total body CT scan showed bilateral pleural effusion and hilar mesenterial, abdominal, and paratracheal lymphadenopathy. Lymphoproliferative disease with HLH complication was therefore suspected. High doses of glucocorticoids were then administered. A cytologic analysis of the pleural effusion showed anaplastic lymphoma cells and bone marrow aspirate showed hemophagocytosis. An Epstein-Barr Virus (EBV) DNA load of more than 90000 copies/mL was found. Bone marrow biopsy showed a marrow localization of peripheral T lymphoma. The course was rapidly progressive until the patient died. HLH is a rare but usually fatal complication in adults of hematologic, autoimmune, and malignant diseases. Very early diagnosis and treatment are critical but not always sufficient to save patients.

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Giant cell arteritis (GCA) is a noninfectious granulomatous vasculitis of unknown etiology affecting individuals older than 50 years. Two forms of GCA have been identified: a cranial form involving the medium-caliber temporal artery causing temporal arteritis (TA) and an extracranial form involving the large vessels, mainly the thoracic aorta and its branches. GCA generally affects individuals with a genetic predisposition, but several epigenetic (micro)environmental factors are often critical for the onset of this vasculitis. A key role in the pathogenesis of GCA is played by cells of both the innate and adaptive immune systems, which contribute to the formation of granulomas that may include giant cells, a hallmark of the disease, and arterial tertiary follicular organs. Cells of the vessel wall cells, including vascular smooth muscle cells (VSMCs) and endothelial cells, actively contribute to vascular remodeling responsible for vascular stenosis and ischemic complications. This review will discuss new insights into the molecular and cellular pathogenetic mechanisms of GCA, as well as the implications of these findings for the development of new diagnostic biomarkers and targeted drugs that could hopefully replace glucocorticoids (GCs), still the backbone of therapy for this vasculitis.

Fibromyalgia symptoms affect the sufferers' working life; however, through reasonable accommodations in workplaces, they can continue to work satisfactorily. There are no Italian studies on factors that facilitate or hinder fibromyalgia-affected people's working life. Our objective was to explore, in a pre-pandemic setting, the quality of working life of fibromyalgia sufferers and reasonable accommodations to improve it. Quantitative and qualitative methods were applied; a survey-questionnaire, participatory-developed, was online-administered to a sample of self-reported FM sufferers (N = 1176). Then, two Focus Groups (FGs), involving 15 fibromyalgia-affected women, were held. Data were analyzed by a thematic analysis approach. Among survey-respondents, 20% were unemployed and only 14% went to work gladly. Variability of pain (84%) and fatigue (90%) were the most perceived reasons for difficulties at work. Negative relationships at work were reported by most participants. The FGs' discussions addressed different strategies for overcoming the main obstacle of "not being believed by colleagues and employers" and reasonable accommodations. However, a negative hopeless attitude towards the solution of problems at work was also apparent. Different critical issues in the workplace emerged from the survey and the FGs. Coordinated actions, according to a transdisciplinary approach, are needed to manage fibromyalgia-induced difficulties in the workplace.

Seronegative rheumatoid arthritis (SNRA) is characterized by the absence of both rheumatoid factor (RF) and antibodies against the cyclic citrullinated protein (ACPA) in serum. However, the differences between the two forms of RA are more complex and have not yet been definitively characterized. Several lines of evidences support the idea that there are specific elements of the two forms, including genetic background, epidemiology, pathogenesis, severity of progression over time, and response to therapy. Clinical features that may differentiate SNRA from SPRA are also suggested by data obtained from classical radiology and newer imaging techniques. Although new evidence seems to provide additional help in differentiating the two forms of RA, their distinguishing features remain largely elusive. It should also be emphasized that the distinctive features of RA forms, if not properly recognized, can lead to the underdiagnosis of SNRA, potentially missing the period called the "window of opportunity" that is critical for early diagnosis, timely treatment, and better prognosis. This review aims to summarize the data provided in the scientific literature with the goal of helping clinicians diagnose SNRA as accurately as possible, with emphasis on the most recent findings available.

Objective: To investigate mindfulness traits/attitudes as protective factors against chronic pain related distress, depression and anxiety., Method: Fifty patients (25 with chronic non-oncologic pain-NOP; 25 with chronic oncologic pain-COP) were administered with the following scales: Visual Analogue Scale (VAS), Pain Disability Index (PDI), Italian Questionnaire for Pain (QUID), Perceived Stress Scale (PSS), State and Trait Anxiety Scale (STAY-y1 module), Beck Depression Inventory II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Psychological General Well Being Index (PGWBI), Mindful Attention Awareness Scale (MAAS)., Results: MAAS value ≥ 4.38 was adopted as cut-off to compare ' high level of mindfulness ' (HM) vs. ' normal level of mindfulness ' (NM) attitudes. Twenty-six patients (52%) scored ≥4.38, with no different distribution between NOP and COP. HM patients scored significantly lower than NM patients on PDI 'family/home responsibilities' domain (4.5±3.2 vs. 6.4±2.8; p<.037), and on PSS (17.8±2.6 vs. 20.9±2.5; p<.0001), STAY-y1 (9.4±1.8 vs. 10.3±2.1; p<.0001), BDI-II (7.8±5.0 vs. 17.6±8.6; p<.0001) total scores. HM scored significantly higher than NM patients in all PGWBI domains. A multiple regression analysis was carried out to analyze the predictor variables of PGWB. The most complete model considered the variables MAAS, STAIy and VAS (F=42.21; p<.0001), that accounted for the 71.6% of PGWB variance. MAAS score was the only variable positively predicting for PGWB; STAIy and VAS scores predicted negatively., Conclusions: Chronic pain patients with high levels of mindfulness attitudes experienced less distress, anxiety, depressive symptoms, and more physical and general wellbeing than patients with low levels of mindfulness attitudes., Competing Interests: Competing interests: None., (© 2023 Giovanni Fioriti Editore s.r.l.)

The human leukocyte antigen (HLA)-B*27 family of alleles is strongly associated with ankylosing spondylitis (AS), a chronic inflammatory disorder affecting the axial and peripheral joints, yet some HLA-B*27 variants not associated with AS have been shown. Since no major differences in the ligandome of associated compared to not-associated alleles have emerged, a plausible hypothesis is that the quantity rather than the quality of the presented epitopes makes the difference. In addition, the Endoplasmic Reticulum AminoPeptidases (ERAPs) 1 and 2, playing a crucial role in shaping the HLA class I epitopes, act as strong AS susceptibility factors, suggesting that an altered peptidome might be responsible for the activation of pathogenic CD8+ T cells. In this context, we have previously singled out a B*27:05-restricted CD8+ T cell response against pEBNA3A (RPPIFIRRL), an EBV peptide lacking the B*27 classic binding motif. Here, we show that a specific ERAP1/2 haplotype negatively correlates with such response in B*27:05 subjects. Moreover, we prove that the B*27:05 allele successfully presents peptides with the same suboptimal N-terminal RP motif, including the self-peptide, pDYNEIN (RPPIFGDFL). Overall, this study underscores the cooperation between the HLA-B*27 and ERAP1/2 allelic variants in defining CD8+ T cell reactivity to suboptimal viral and self-B*27 peptides and prompts further investigation of the B*27:05 peptidome composition.

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.

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.

Introduction: The aim of this case series was to assess the safety and effectiveness of peripheral nerve stimulation (PNS) of the brachial plexus performed using a low invasive percutaneous approach with ultrasound guide., Materials and Methods: Patients affected by neuropathic pain with a documented brachial plexus partial avulsion were included in this observational study. A totally implantable PNS system specifically designed for peripheral placement (Neurimpulse, Padua, Italy) was implanted and followed for 18 months, recording the level of pain (Numeric Rating Scale [NRS]), therapy satisfaction (Patient Global Impression of Improvement), quality of life (Short Form Health Survey questionnaire), and change in drug consumption and work status. Descriptive statistic (mean and SD) was used to compare pre- and postimplantation differences., Results: A total of 18 patients were included in the observational study; 16 of them proceeded with the permanent implantation. System infection (N = 1) and lead migrations (N = 2) were recorded during a follow-up mean of 14.8 ± 5.4 months. The average NRS reduction at 18 months was 41%. Average quality-of-life physical and mental indexes increased by 14% and 32%, respectively. Drug intake was stopped in 22% and reduced in 56% of the patients., Conclusions: PNS systems of the brachial plexus implanted with percutaneous approach appear to be safe and effective in a follow-up period of 18 months. Longer and larger studies are needed to confirm and extend these outcomes., (Published by Elsevier Inc.)

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare systemic diseases affecting small-caliber vessels. The damage caused by AAV mainly involves the lung and kidneys. AAV includes three different types: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Although the different phenotypic forms of AAV share common features, recent studies have shown that there are significant differences in terms of pathogenetic mechanisms involving both the adaptive and innate immune systems. Advances in our understanding of pathogenesis have enabled the development of immuno-targeted therapies. This review illustrates the characteristics of the various forms of AAV and the new therapies available for this disease that can have lethal consequences if left untreated.

Background: Most of the recent literature regarding rotator cuff tear etiology identifies in peripheral microcirculation disorders the probable main cause of tissue degeneration, and consequently of tendon rupture. Nailfold capillaroscopy is a practical and inexpensive diagnostic technique used to evaluate the health status of peripheral microcirculation, and recently, its use has found other indications in addition to that of diagnosing connective tissue diseases and Raynaud phenomenon. We verified the possible indirect contribution of nailfold capillaroscopy in the identification of peripheral microcirculation disturbances in a group of patients with rotator cuff tear and whether these possible alterations could be related to rotator cuff tear size., Materials and Methods: A case-control study was performed. One hundred patients (56 male, 44 female; mean age ± standard deviation [SD]: 60.46 ± 5.46 years) with different-sized posterosuperior cuff tears and 100 healthy controls (38 male, 62 female; mean age ± SD: 60.40 ± 6.34 years) were submitted to capillaroscopic examination. The following parameters were examined: capillary morphology and density, avascular areas, visibility of the subpapillary venous plexus, enlarged and giant capillaries, ectasias and microaneurysms, neoangiogenesis, hemosiderin deposits, pericapillary edema, and capillary blood flow. Severe exclusion criteria were applied. Statistical analysis was performed., Results: Visibility of subpapillary venous plexus (P < .001), pericapillary edema (P < .001), capillary blood flow (P < .001), ectasias and microaneurysms (P < .001), and neoangiogenesis (P = .04) were significantly associated with presence of a rotator cuff tear., Conclusions: Our results support the hypothesis that microcirculation disorder has a relevant role in the genesis of cuff degeneration and, consequently, of tendon rupture. However, these alterations do not seem to be related to rotator cuff tear size., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response., Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months., Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% ( n = 125) and 54.9% ( n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01)., Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. This condition causes stiffness, pain, and significant limitation of movement. In recent years, several effective therapies have become available based on the use of biologics that selectively block cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor-α (TNFα), interleukin (IL)-17, and IL-23. However, a significant number of patients show an inadequate response to treatment. Over 10 years ago, small synthetic molecules capable of blocking the activity of Janus kinases (JAK) were introduced in the therapy of rheumatoid arthritis. Subsequently, their indication extended to the treatment of other inflammatory rheumatic diseases. The purpose of this review is to discuss the efficacy and safety of these molecules in axSpA therapy.

Objectives: To support rational decision-making on spinal cord stimulation (SCS), a European expert panel developed an educational e-health tool using the RAND/University of California at Los Angeles Appropriateness Method. This retrospective study aimed to determine the applicability and validity of the tool using data from patients for whom SCS had been considered., Materials and Methods: A total of 12 European implant centers retrieved data from 25 to 50 consecutive patients for whom SCS was considered in 2018-2019. For each patient, data were captured on the clinical and psychosocial variables included in the e-health tool, center decisions on SCS, and patient outcomes. Patient outcomes included global perception of effect by the patient and observer, and pain reduction (numeric pain rating scale) at six-month follow-up., Results: In total, 483 patients were included, of whom 133 received a direct implant, 258 received an implant after a positive trial, 32 had a negative trial, and 60 did not receive SCS for reasons other than a negative trial. The most frequent indication was persistent spinal pain syndrome type 1 and type 2 (74%), followed by neuropathic pain syndromes (13%), complex regional pain syndrome (12%), and ischemic pain syndromes (0.8%). Data on the clinical and psychosocial variables were complete for 95% and 93% of patients, respectively, and missing data did not have a significant impact on the study outcomes. In patients who had received SCS, panel recommendations were significantly associated with patient outcomes (p < 0.001 for all measures). Substantial improvement ranged from 25% if the e-health tool outcome was "not recommended" to 83% if SCS was "strongly recommended". In patients who underwent a trial (N = 290), there was 3% of trial failure when SCS was "strongly recommended" vs 46% when SCS was "not recommended"., Conclusions: Retrospective application of the e-health tool on patient data showed a strong relationship between the panel recommendations and both SCS trial results and treatment outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability to produce members of the interleukin-17 (IL-17) family, namely IL-17A and IL-17F. IL-17 in turn induces several target cells to synthesize and release cytokines, chemokines, and metalloproteinases, thereby amplifying the inflammatory cascade. Th17 cells reside predominantly in the lamina propria of the mucosa. Their main physiological function is to maintain the integrity of the mucosal barrier against the aggression of infectious agents. However, in an appropriate inflammatory microenvironment, Th17 cells can transform into immunopathogenic cells, giving rise to inflammatory and autoimmune diseases. This review aims to analyze the complex mechanisms through which the interaction between Th17 and pathogens can be on the one hand favorable to the host by protecting it from infectious agents, and on the other hand harmful, potentially generating autoimmune reactions and tissue damage.

Background and Objectives : To investigate the etiology, clinical features, ocular complications, and visual outcomes in children with infectious uveitis referred to a tertiary uveitis hospital-based service. Materials and Methods : Children with infectious uveitis were included in a retrospective cohort study. The data set was obtained after reviewing the medical records of pediatric patients with uveitis of different causes referred to our center during the period from 2009 to 2019. Clinical evaluations were performed at the time of diagnosis and the end of follow-up. Results : Uveitis of infectious origin was present in 57 (72 eyes) of 314 (18.1%) patients examined. The median age at presentation was 10.9 years (6.1-15.8), 52.6% of patients were female, and 47.4% were male. The main cause of infectious uveitis was viral (56.1% of cases), followed by Toxoplasma gondii infection (24.5%). The anatomical location of uveitis was posterior in 40.3%, anterior in 36.8%, panuveitis in 15.7%, and intermediate in 7% of cases. Ocular involvement was unilateral in 42 children (73.7%) and bilateral in 15 (26.3%) cases. The main causes of reduced visual acuity were cataract and maculopathy in 57.1% and 28.5% of cases, respectively. During the follow-up period, 75% of patients showed significant improvements in visual acuity. Conclusions : Specialist management in a tertiary referral eye care center facilitates early diagnosis and effective treatment of this serious cause of morbidity and vision loss in children.

Background and Objectives : Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. Materials and Methods : In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23-IL-17 axis, by reporting updated findings from the scientific literature. Results: Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). Conclusions: IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.

Objective: There are few real-world setting studies focused on apremilast effectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention rate in real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and the factors related to treatment persistence., Methods: In fifteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant., Results: The 356 enrolled patients (median age 60 [interquartile range IQR 52-67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7-34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefficacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefficacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96-0.99; p = 0.048 and 0.54 IQR 0.31-0.95; p = 0.03)., Conclusion: Almost three-fifths of PsA patients receiving apremilast were still in treatment after 3 years. This study confirmed its effectiveness and safety profile. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbidities. Key Points • Apremilast retention rates in this real-life cohort and trials are comparable. • The oligo-articular phenotype is associated with long-lasting treatment (i.e., 3 years). • No different or more prevalent adverse events were observed., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: A previously developed educational e-health tool considers both clinical and psychosocial factors when selecting patients with chronic pain for spinal cord stimulation (SCS). The validity of the composite recommendations was evaluated in a retrospective study, demonstrating a strong relationship with patient outcomes after SCS., Methods: An additional retrospective analysis was performed to determine the added value of a psychosocial evaluation as part of the decision-making process on SCS. Data concerned 482 patients who were considered for SCS in 2018-2019. The analysis focused on the relationship between the different layers of the tool recommendations (clinical, psychosocial, composite) with trial results and patient outcomes at 6 months after SCS. Of the initial study population, 381 patients underwent SCS and had follow-up data on at least one of three pain-related outcome measures., Results: Pain improvement was observed in 76% of the patients for whom SCS was strongly recommended based on merely the clinical aspects. This percentage varied by the level of psychosocial problems and ranged from 86% in patients without any compromising psychosocial factors to 60% in those with severe problems. Similarly, the severity of psychosocial problems affected trial results in patients for whom SCS was either recommended or strongly recommended., Conclusions: The strong relationship between psychosocial factors embedded in the SCS e-health tool and patient outcomes supports an integrated and multidisciplinary approach in the selection of patients for SCS. The educational e-health tool, combining both clinical and psychosocial aspects, is believed to be helpful for further education and implementation of this approach., Significance Statement: This study confirms the relevance of the psychosocial factors embedded in the educational SCS e-health tool (https://scstool.org/). The strong relationship between the severity of psychosocial factors with patient outcomes supports conducting a comprehensive psychological and behavioural assessment when determining the eligibility of patients for SCS., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

We describe the unusual case of a young woman with tubulointerstitial nephritis and uveitis (TINU) with bilateral diffuse uveitis and optic nerve inflammatory involvement since she was a child in the 1990s. Imaging diagnostic tools such as fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography revealed inactive juxtapapillary choroidal neovascularization (CNV) after 25 years of follow-up. After treatment, uveitis went into remission with BCVA 20/20 in both eyes and CNV lesions became inactive. Although anterior uveitis is more frequently reported in TINU, posterior uveitis with inflammatory involvement of the optic nerve should be accurately investigated to rule out juxtapapillary CNV, both at the time of active uveitis and during follow-up, since TINU may be complicated by CNV even at the later stages of the inflammatory process.

Background: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with tubulointerstitial nephritis (TIN). However, the prevalence and clinical features of TINU are still a matter of debate. To add information about TINU, we describe here the clinical features of a series of patients affected by TINU in a retrospective study., Methods: A total of 9358 clinical records of both adult and pediatric patients up to 21 years of age, referred to the Uveitis Center of the Sapienza University of Rome, were examined. The medical records covered a period from 1990 to 2020. Various demographic and clinical features were analyzed in patients who met the criteria for TINU., Results: Twenty-one patients with TINU were identified. TINU was classified as definite, possible, or probable by the currently recognized international criteria. The median age at diagnosis was 14 years (interquartile range 12-35). Females were predominant (15/21, 71.4%). In most cases (14/21, 66.6%), patients developed ocular disease concurrently with renal disease. The most frequent type of ocular involvement was bilateral anterior uveitis (9/21, 42.8%). In two cases, patients presented with bilateral intermediate uveitis; in three cases, they presented with bilateral or unilateral alternating posterior uveitis; and in four cases, they presented with bilateral panuveitis. In one case, the uveitis was anterior in the right eye (OD) and posterior in the left eye (OS), and two cases presented with bilateral asynchronous or unilateral alternating anterior uveitis. All patients received treatment with systemic corticosteroids and topical ocular therapy. At the end of the follow-up, a significant improvement in ocular signs and symptoms with a return to normal visual acuity was generally observed. In all patients, acute kidney injury (AKI) reverted completely and none progressed to chronic kidney disease (CKD)., Conclusions: Patients with TINU may often present with atypical uveitis. We suggest that patients with sudden-onset uveitis, even if not bilateral anterior, should be referred to a nephologist for an assessment of the possible presence of renal disease.

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother−infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period.

Objectives: Fibromyalgia is a severe and disabling chronic pain syndrome affecting millions of people worldwide. Various patients' subgroups were identified using different atheoretical measures, hardly effective to tailor treatments. Previous literature findings showed the relevance of fibromyalgia patients' illness perceptions in adjusting to the disease. The present study aims to identify clusters of fibromyalgia patients based on their illness perceptions and investigate whether they can differ across pain, mood, physical functioning, catastrophising, and pain acceptance measures., Methods: Fifty-three newly referred fibromyalgia patients completed clinical and psychological questionnaires. Patients' subgroups were created by applying hierarchical cluster analysis to their answers to Illness Perception Questionnaire-Revised subscales. Potential differences across subgroups in outcome variables were tested., Results: Cluster analysis identified two patient groups. Group A (32 patients) had a higher representation of fibromyalgia as a chronic disease with severe consequences, lower beliefs in personal and treatment control, and a higher fibromyalgia-related emotional distress than group B (21 patients). Clusters did not differ on pain intensity and duration. Group A, compared to group B, showed worse physical functioning and overall impairment due to fibromyalgia, a poorer psychological condition, a higher tendency to catastrophise, and less pain acceptance., Conclusions: Study findings reveal two fibromyalgia subgroups differing in emotional suffering and impairment despite similar pain intensity and duration. Patients' illness perceptions and attitudes towards pain, like catastrophising and acceptance, might be critical in adjusting to the disease. A detailed assessment of such risk and protective factors is critical to differentiate patients' subgroups with different needs and thus offering tailored treatments.

Background: Juvenile idiopathic arthritis (JIA) is a rheumatic condition of childhood that is frequently associated with anterior chronic uveitis. Evidence suggests that uveitis may persist up to adulthood in some cases, possibly causing severe visual impairment. Methods: We conducted a retrospective study on a series of patients aged 16 years or older with JIA-related active uveitis who were referred to the Uveitis Service of Sapienza University of Rome from 1990 to 2019 to evaluate the characteristics of ocular disease in patients with JIA-associated uveitis (JIA-U) who still exhibit uveitis in adulthood. Data on clinical features, treatment, complications and visual outcomes were collected. Results: Twenty adults (85% female; median age 23.4 ± 6.6 years, range 16−38 years) with ongoing uveitis (35 eyes) were identified. The median age at JIA onset was 6.15 ± 2.9 years (range 2−10), and uveitis onset was 8.7 ± 4.7 years (range 3−20). The patients were observed in a median follow-up of 16 ± 7.7 years (range 4−35). Fifty-seven percent of affected eyes (20 eyes) had good visual acuity (>0.4 logMAR), while eleven percent of affected eyes (4 eyes) were blind (≤20/200). Uveitis required topical steroids and mydriatic/cycloplegic in all cases. Orbital steroid injection was performed in 13 eyes. Systemic corticosteroids and biologic drugs were used in 14 patients. Conclusions: Although the visual prognosis of JIA-U has improved in recent years, persistent uveitis up to adulthood is still observed. Therefore, protracted follow-up of JIA-U patients is warranted because of the high burden of delayed visual complications.

CD8 + T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8 + T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8 + T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.