Upadacitinib (UPA) is approved for moderate-to-severe rheumatoid arthritis (RA) based on SELECT trials, but data on real-world effectiveness are limited. UPHOLD is a multicountry study of patients with RA receiving UPA 15 mg. The present interim analysis was based on the Italian cohort performed across 28 centers. Co-primary endpoints were (i) the proportion of patients receiving UPA who achieved DAS28(CRP) remission (< 2.6) at 6 months and (ii) the proportion of patients achieving DAS28(CRP) remission at 6 months who continued to receive UPA and maintained remission (or had no more than a 0.6-point increase in DAS28[CRP]) at 12 months, analyzed by modified non-responder imputation (mNRI) and as observed (AO). Modified full analysis sets (mFAS1 and mFAS2) included patients completing 6 and 12 months, respectively. Safety analysis included reporting of adverse events and treatment-emergent adverse events (TEAEs), as exposure-adjusted event rates (EAERs; events per 100 patient-years [E/100PY]). Among 270 patients, 74 (27.4

ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.

Orbital inflammation is the most common presentation of VEXAS, with any orbital structure potentially affected. Non-sight-threatening and uncomplicated anterior non-granulomatous uveitis and anterior diffuse scleritis follow in frequency, along with episcleritis. Ophthalmic involvement was significantly associated with relapsing polychondritis (p = 0.014), with an increased chance of a fatal outcome (RR 5.87, p = 0.016) and independently predicts a higher mortality rate (OR 3.72, p = 0.026). Treatment of ophthalmic involvement showed full or partial response to glucocorticosteroids alone in 66.7% of cases. Ophthalmic involvement is common in VEXAS syndrome and signals a poorer prognosis in terms of mortality, highlighting the need for close monitoring.

IntroductionRecurrent febrile episodes account for one of the most frequent symptoms observed in Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome and a key target for therapeutic intervention. Therefore, this study aims at investigating the association between recurrent febrile episodes and specific clinical manifestations, mortality and response to treatment.MethodsData were obtained from the international AutoInflammatory Disease Alliance (AIDA) Network registry and analyzed using a Bayesian statistical approach. Posterior probabilities [P(β)] were calculated to assess the likelihood that fever was associated with clinical, laboratory, genetic, and therapeutic features.ResultsIn total, 87 VEXAS patients were enrolled, 65 (74.7%) of whom suffered from recurrent fever episodes. Fever episodes showed a significant association with patients’ mortality [P(β): 99.41%], as well as with major inflammatory organ involvement, including cardiac [P(β): 99.99%], lung [P(β): 99.98%], and gastrointestinal [P(β): 97.5%] involvement. The occurrence of recurrent fever episodes was associated with a negligible probability of both complete response and treatment failure [P(β) <2.5%], instead favoring a partial response [P(β) >97.5%] to conventional disease modifying anti-rheumatic drugs, Janus Kinases inhibitors, and tocilizumab. For temperatures exceeding 40 °C, using anti-interleukin-1 agents was associated with a high probability of treatment failure [P(β): 99.3%].Conclusionsfebrile episodes are associated with more severe pattern of organ involvement and, accordingly, to death. Furthermore, febrile episodes could correlate with differential therapeutic responsiveness, thereby potentially serving as a valuable marker to guide the treatment strategies in VEXAS patients.

OBJECTIVES:Among the myositis specific antibodies (MSAs), the antisynthetase (anti-ARS) and the anti-MDA5 antibodies are those more frequently characterised by the occurrence of joint involvement. We aim to define the prevalence of MSAs in patients with established rheumatoid arthritis (RA), psoriatic arthritis (PsA), or undifferentiated polyarthritis (UPA). METHODS:From January 2021 to December 2024, all RA, PsA and UPA patients prospectively followed in our Early Arthritis Clinic (EAC), were evaluated. Changes in diagnosis, clinical/laboratory signs of muscle/lung/skin involvement at onset or during the follow-up, overlap syndromes, anti-ENA or cytoplasmic ANA positivity, Raynaud's phenomenon, and less than 24 months of follow-up were exclusion criteria. Baseline serum samples were tested for MSAs (line-blot). Positivity was defined according to manufacturers' instructions. RESULTS:143 patients were enrolled (93 females, 65%; 67 AR, 47%; 50 UPA, 35%, 26 PsA, 18%). Line-blot resulted positive in 10 (7%), weak-positive in 12 (8%), and borderline in 26 cases (18%). The remaining 95 patients (67%) were negative. MSAs positivity was anti-cN1A in 3 cases and anti-ARS and anti-MDA in 4 cases each. Weak positivity was found for anti-ARS (4), and anti-PM-Scl75 (3). Borderline results showed a high number of anti-ARS and aMDA5 (12, 46%). No variables were associated with MSA positivity. CONCLUSIONS:MSAs positivity may be observed in one third of patients with primary isolated arthritis. About half of these cases displayed full or weak positivity for MSAs, whereas the remaining half displayed borderline results. Clinicians should be aware that MSA should be assessed only in case of effective clinical need.

OBJECTIVE:Rheumatic and musculoskeletal diseases (RMDs) represent a significant public health challenge in Italy. RMDs are often chronic and lead to increased morbidity and mortality, partly due to an increased risk of infections. Patients with RMDs and those on immunosuppressive therapy show a higher susceptibility to vaccine-preventable diseases and to serious complications in case of infection. Therefore, vaccination is a crucial tool to reduce these risks. This guideline was developed by the Italian Society of Rheumatology and aimed to provide updated national recommendations for clinical practice on vaccinations in adult patients with RMDs. METHODS:The GRADE ADOLOPMENT approach to combine adoption, adaptation, or de novo development of recommendations was used, and the 2022 American College of Rheumatology (ACR) guideline on vaccinations in RMDs was used as reference. The development process included an updated systematic review of the available evidence and an assessment of the ACR guidelines and their adaptability to the Italian context, followed by a discussion with experts in rheumatology and public health and representatives of healthcare professionals and patients. RESULTS:A set of recommendations was developed, and special attention was given to the current vaccination schedule and to the adjustment of anti-rheumatic drugs to optimize the response to vaccines. CONCLUSIONS:This guideline is a step forward in enhancing management and clinical practice for RMD patients in Italy and provides specific and evidence-based indications for infection prevention through vaccination. Their use is intended to promote health and alleviate the burden of morbidity and mortality in this vulnerable population.

Scleritis is a rare and severe ocular inflammatory disease that is often associated with potentially sight-threatening ocular complications. The aim of the present study was to characterize ocular complications in non-infectious scleritis and identify predictive variables for their development. Data for this registry-based study were extracted from the AutoInflammatory Disease Alliance Network for Scleritis Registry. Univariate analysis was performed to examine potential associations of demographic and clinical variables with the development of ocular complications. Uveitis and peripheral ulcerative keratitis were considered to be extensions of the inflammatory process and not to be true structural complications. Predictive factors of ocular complications were assessed using regression analysis. The impact of ocular complications on visual acuity—measured by best-corrected visual acuity (BCVA)—was also analyzed. A total of 154 patients (218 eyes) with non-infectious scleritis were enrolled. In 58 of these patients (87 eyes), 102 ocular complications were recorded, with cataract, scleral and corneal thinning, and glaucoma and/or increased ocular pressure being the most frequently recorded complications. Ocular complications were found to be significantly more frequent among patients affected by granulomatosis with polyangiitis (GPA) (p < 0.0001) and concomitant uveitis (p = 0.023). The mean severity score was significantly higher among eyes experiencing ocular complications (p < 0.0001). Regression analysis identified three variables capable of predicting the development of ocular complications: a diagnosis of GPA [odds ratio (OR) 7.747, p < 0.0001]; the presence of concomitant uveitis (OR 3.648, p = 0.019); and a high severity score (OR 1.138, p = 0.044). Mean (± standard deviation) BCVA converted to logMAR was found to be significantly higher among eyes without ocular complications (0.12 ± 0.24 vs 0.27 ± 0.49; p = 0.005). Scleritis was accompanied by irreversible ocular complications in a considerable proportion of the patients enrolled in this study. Patients with a diagnosis of GPA, concomitant uveitis, and a higher severity score are more likely to develop ocular complications, and thus warrant a tighter follow-up schedule and early treatment in order to minimize the risk of poor visual prognosis.

ObjectivesTo evaluate the therapeutic management of patients with active adult-onset Still’s disease (AOSD) in a multicentre real-world setting and to provide and compare current real-world treatment strategies with existing recent international recommendations.MethodsFrom January 2022 to December 2023, 173 consecutive patients with active AOSD attending centres participating in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD research study group were prospectively enrolled. Demographic, clinical, and laboratory data were collected, and therapeutic strategies prescribed by the treating physicians were systematically recorded. Factors associated with the administration of biologic disease-modifying antirheumatic drugs (bDMARDs), including IL-1 and IL-6 inhibitors, were analysed.ResultsGlucocorticoids were administered in 97.7% of patients. Conventional synthetic DMARDs were prescribed in 58.8% of cases, mainly methotrexate and cyclosporin A. Overall, 43.3% of patients received bDMARDs, predominantly IL-1 and IL-6 inhibitors. Specifically, 33.5% were treated with IL-1 inhibitors, 5.8% with IL-6 inhibitors, and 4.0% with tumour necrosis factor inhibitors. After three months of treatment, 86.7% of patients achieved clinical inactive disease as assessed by the treating physician. Comparing recorded treatment strategies with international recommendations, no compliance was found regarding the use of glucocorticoids, which are recommended to be markedly limited or avoided, and early administration of bDMARDs, which were administered within 3 months in a minority of patients.ConclusionsThis multicentre real-world study outlines current therapeutic approaches for patients with active AOSD and highlights a gap between international treatment recommendations and clinical practice, underscoring the need for further studies to optimize patient management.

Objectives To evaluate whether early canakinumab initiation may provide treatment advantages in Still’s disease (SD) patients, particularly in terms of therapy discontinuation due to long-term disease remission, glucocorticoid sparing effect, and increase in the frequency of monocyclic disease course rather than a polycyclic or chronic articular pattern. Methods SD patients treated with canakinumab were grouped according to time between disease onset and canakinumab initiation (≤3 months vs. >3 months). Patients were enrolled from the international AutoInflammatory Disease Alliance (AIDA) Network registry for SD. Results Overall, 190 patients were enrolled, 35 (19%) treated with canakinumab within three months from SD onset and 155 (82%) starting canakinumab later. Glucocorticoids use decreased more rapidly in patients receiving canakinumab within 3 months from SD onset than among patients treated later, with reductions of 50% vs 6% at month 3 (p=0.0001), and 75% vs 32% at month 6 (p=0.004). In logistic regression analysis, canakinumab initiation within 3 months from disease onset was significantly associated with treatment discontinuation due to long-term remission (OR 4.83, 95% CI 1.08-23.19; p=0.04). A monocyclic course occurred in 49% of patients starting canakinumab ≤3 months versus 8% starting later (p<0.0001). Starting canakinumab within 3 months from disease onset was significantly associated with a monocyclic disease course compared with the chronic-articular (RRR 4.43, 95% CI 1.12-17.60; p=0.034) and polycyclic courses (RRR 8.97, 95% CI 1.29-62.3; p=0.03). Conclusions Early canakinumab initiation is associated with treatment discontinuation due to long-term remission and appears linked to a greater frequency of a monocyclic disease course.

Background:A substantial overlap in demographic, clinical, and laboratory features can complicate the differential diagnosis between Schnitzler's syndrome and VEXAS syndrome. The present study was undertaken to identify clinical and laboratory parameters that should raise suspicion for VEXAS syndrome among patients previously diagnosed with, or under evaluation for, Schnitzler's syndrome. Methods:Data from male-only patients with Schnitzler's syndrome or VEXAS syndrome were obtained from international AIDA Network registries. Subjects with Schnitzler's syndrome were compared to VEXAS patients with urticarial skin manifestations resembling cutaneous features typically observed in Schnitzler's syndrome. Results:A total of 19 VEXAS patients and 18 patients with Schnitzler's syndrome were enrolled. At univariate binary logistic regression, the diagnosis of VEXAS syndrome was associated with the age at disease onset (OR = 1.08, 95% CI. 1.01-1.16, p = 0.02), hemoglobin levels (OR = 0.44, 95% CI. 0.26-0.77, p = 0.003), anemia (OR = 13.9, 95% CI. 3.4-5.7, p = 0.02), leucocytosis (OR = 0.04, 95% CI. 0.06-0.22, p < 0.001), lymphadenopathy (OR = 7.8, 95% CI. 1.41-45.4, p = 0.02), and thrombocytopenia (OR = 13.5, 95% CI. 1.47-123.7, p = 0.02). In the multivariable logistic regression analysis with the stepwise forward selection approach, the diagnosis of VEXAS syndrome was significantly associated with the age at disease onset (OR: 1.13, 95% CI: 1.02-1.30, p = 0.04) and the presence of lymphadenopathy (OR: 67.49, 95% CI: 5.36-3284.89, p = 0.007), while thrombocytopenia showed a trend toward statistical significance (OR: 12.02, 95% CI: 1.07-315.86, p = 0.06). Conclusions:Patients with lymphadenopathy, thrombocytopenia, anemia, particularly in older age and in the absence of leucocytosis, are more likely to be affected by VEXAS syndrome rather than Schnitzler's syndrome.

OBJECTIVES:The progression of Behçet's disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. METHODS:Patients' data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. RESULTS:A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22-0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44-113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1-5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15-7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22-11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08-7.58, P = 0.03). CONCLUSION:A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.

ObjectivesThis study aims to explore the application of machine learning techniques in assessing macrophage activation syndrome (MAS) in Still’s disease.MethodsA multicenter, observational, prospective study was conducted, including patients with Still’s disease enrolled in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD Study Group and the AutoInflammatory Disease Alliance (AIDA) Network Still’s Disease Registry.ResultsA total of 737 patients (age: 35.5 ± 17.8, male sex: 44.7%) with Still’s disease were assessed; 11.4% were affected by MAS, and 3% had a poor prognosis. First, random forest imputation was applied to the original dataset. Subsequently, a machine-learning-driven assessment was developed to explore MAS occurrence. Collectively, regression models, an exploration decision tree, and a random forest were applied, suggesting the importance of ferritin, age, C-reactive protein (CRP), and systemic score. A logistic regression model accounting for data leakage concerns was then generated using these variables, and missing values were imputed using random forest imputation. This analysis supported the role of the selected variables, which were further combined across different clinical scenarios to estimate the probability of MAS. The highest risk of MAS was estimated for patients simultaneously characterized by age ≥ 45 years, ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and a systemic score ≥ 7, corresponding to a 34.7% probability of MAS, as well as for those characterized by ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and systemic score ≥ 7, corresponding to a 33.5% probability of MAS.ConclusionsA machine-learning-driven prediction of MAS was explored in Still’s disease, highlighting the importance of age of onset, hyperferritinaemia, increased CRP, and multiorgan involvement. A combination of these features may suggest a clinician-friendly algorithm for stratifying the probability of MAS during Still’s disease.

BACKGROUND:VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an acquired autoinflammatory disorder characterized by severe chronic inflammation and an increased occurrence of hematologic neoplasms. Although chronic inflammation is a well-established risk factor for cancer, the specific contribution of UBA1 gene mutations to tumorigenesis remains unclear. Therefore, this study aimed to evaluate the overall cancer risk in patients with VEXAS syndrome, including both hematologic and non-hematologic neoplasms. METHODS:The relative risk (RR) of cancer was compared between VEXAS patients and a control cohort comprising individuals with Still's disease, Behçet's disease, and Schnitzler's syndrome. Logistic regression analysis was performed to identify variables potentially associated with cancer development. Patient's data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries for VEXAS syndrome, Still's disease, Behçet's disease, and Schnitzler's syndrome. RESULTS:Ninety-six VEXAS patients and 2181 controls were enrolled. To minimize selection bias, only subjects aged >60 years were included, yielding 90 and 174 individuals in the exposed and control groups, respectively. The overall RR for cancer in VEXAS patients was 1.93 (95 % Confidence Interval [C.I.] 1.03-3.60, p = 0.036). Logistic regression analysis identified associations between cancer development and relapsing polychondritis (RR = 2.67, 95 %C.I. 1.22-10.64, p = 0.01), the p.Met41Thr mutation (RR = 3.33, 95 %C.I. 1.29-17.33, p = 0.02), elevated serum erythrocyte sedimentation rate (RR = 1.02, 95 %C.I. 1.01-1.05 p = 0.01), and lactate dehydrogenase (RR = 1.02, 95 %C.I. 1.01-1.07 p = 0.04) levels outside of flares. CONCLUSIONS:VEXAS patients exhibit a significantly increased risk of both hematologic and non-hematologic malignancies compared with controls, particularly among those with RP, p.Met41Thr mutation, and persistent systemic inflammation.

ObjectiveThe primary aim of this study was to assess, in Still’s disease, whether the employment of canakinumab at a strictly on-label dose may increase the likelihood of treatment discontinuation due to study-defined long-term remission (LTR), compared with patients receiving lower doses.MethodsPatients were drawn from the international Autoinflammatory Disease Alliance (AIDA) Network registry dedicated to Still’s disease and stratified based on the starting canakinumab dose: the on-label group received either 300 mg every 4 weeks or 150 mg every 4 weeks (corresponding to 4 mg/kg), while the underdosed group received 150 mg every 4 weeks (corresponding to a dose not exceeding 3.5 mg/kg). Bayesian regression models were implemented to estimate the probability of achieving long-term remission with subsequent canakinumab withdrawal in the two groups, as well as the mean differences in probabilities and posterior probabilities indicating whether the on-label group was superior in achieving the endpoint.ResultsIn total, 131 patients (16.7%) were enrolled, 81 (61.8%) receiving the on-label posology and 50 (38.2%) the underdosed posology. The estimated marginal posterior probability of canakinumab discontinuation due to LTR was 19% (CrI 7.5%–34.6%) in the on-label group and 3.9% (CrI 0.7%–15.2%) in the underdosed group, yielding a mean difference of 15.1% (CrI 1.4%–31.4%) and a posterior probability of 98.4%. This difference remained credible, with posterior probabilities ranging from 97.9% to 99.6%, irrespective of disease course or age at disease onset.ConclusionOn-label canakinumab dosing appears to increase the likelihood of study-defined LTR with subsequent treatment discontinuation, compared with underdosed treatment strategies.

Objectives The interpretation of joint tenderness as a sign of inflammation in patients with autoantibody-negative rheumatoid arthritis (RA) is uncertain. This may hinder disease classification and create selection bias for patient enrollment in clinical trials. Here we tested whether reclassifying the pattern of joint involvement based on swollen joints increases specificity for persistent arthritis in autoantibody-negative early RA. Methods From a prospective early arthritis cohort in the years 2005-2018, all autoantibody-negative patients fulfilling the 2010 ACR/EULAR RA criteria at enrollment were included. Patients were re-classified for the score of swollen joint involvement (1-3=score 2; 4-10=score 3; >10=score 5). Groups were compared for baseline clinical and ultrasonographic (US) characteristics and outcomes after 12 and 36 months. Results Of a total of 354 autoantibody-negative patients with 2010-based RA, 39.5% had a score of swollen joints=5, 47.5% score=3, and 13% score=2. We found equal signs of US synovitis and power Doppler of the wrists and metacarpophalangeal joints. Patients with lower swollen joint scores had similar requirements of treatment intensification within month 12 compared with patients with higher baseline inflammation. These latter had the most favourable outcomes, with lower need of second-line treatment strategies within month 36. Exclusion of patients with concomitant fibromyalgia did not modify the results. Conclusions Joint tenderness should be included in the evaluation of the pattern of joint involvement of the 2010 ACR/EULAR criteria to correctly classify patients with autoantibody-negative early RA. A score solely based on joint swelling may lead to the erroneous under-selection of patients with persistent arthritis.

Behçet’s disease (BD) frequently arises with exclusively mucocutaneous involvement, but some patients will develop major organ involvement, including ocular inflammation. This study aims to assess the patients’ demographic and clinical characteristics that may be associated with the development of ocular involvement in patients with BD with exclusively mucocutaneous involvement in the early stages. Patients’ data were collected in the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. A total of 328 patients with BD were enrolled, 36 (11

OBJECTIVE:Some concerns remain about the safety of nintedanib in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD), such as in the presence of comorbidities or in combination with biologic, targeted synthetic, and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this multicenter study, we retrospectively evaluated the safety of nintedanib in a real-world population of patients with RA-ILD from the Italian Group for the Study of Early Arthritis (GISEA) registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Our secondary aim was to investigate the causes of nintedanib discontinuation. METHODS:Sixty-five patients treated with nintedanib in accordance with the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%). RESULTS:The 12-month retention rate of nintedanib was 76.7% and the drug was effective in about 80% of patients with ≥ 6 months of follow-up. Adverse events (AEs) were recorded in 36 subjects (55.3%), and these were mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed the continuation of the treatment in 22, whereas 15 (23.1%) withdrew from the drug. All reductions and discontinuations were owing to treatment-related AEs. Comorbidities were significantly associated with side effects in multivariate analysis, whereas AEs due to nintedanib were the main cause of discontinuation. CONCLUSION:Combination therapy with DMARDs did not reduce the safety and effectiveness of nintedanib, and AEs were the main cause of drug withdrawal or dose reduction, mainly owing to comorbidities.

OBJECTIVE:To evaluate upadacitinib (UPA) effectiveness on axial and peripheral manifestations of PsA by assessing the proportion of patients achieving low disease activity (LDA) and inactive disease (ID) status for axial involvement, and MDA and DAPSA-defined remission/LDA for peripheral domain. METHODS:This retrospective study included PsA patients from 27 Italian rheumatology centres. Demographic, clinical and outcome data were collected at baseline, 6 and 12 months. Kaplan-Meier curves assessed treatment persistence. Multivariate models identified predictors of discontinuation and outcomes. RESULTS:Among the 425 patients, 282 (66.4%) had peripheral PsA and 143 (33.6%) mixed (peripheral and axial) PsA. The 12-month UPA survival rate was 75.1%, higher in peripheral than mixed PsA (P = 0.039). Fibromyalgia was the strongest predictor of discontinuation (aHR 1.72; 95% CI: 1.08-2.75; P = 0.022). At 12 months, 38.2% of patients achieved ASDAS-LDA and 20.6% reached ASDAS-ID (LUNDEX-adjusted rates were 29.4% and 15.8%, respectively). The crude 12-month MDA rate was 59.9% (47.4% after LUNDEX adjustment). Enthesitis resolved in 80.2% of patients (P < 0.001), and NSAIDs use decreased to 32.9% (P < 0.001). Overall, VAS pain decreased significantly from 71.4 to 40 (mean change -31.4; 95% CI: -42.5 to -33.6; P < 0.0001), with a 44% reduction, well above the minimal clinically important improvement. No major cardiovascular events were reported; most adverse events were mild, including gastrointestinal intolerance (19%), infections (9.5%) and elevated liver enzymes (14.2%). CONCLUSION:Our study confirms UPA effectiveness across PsA domains, with clinically meaningful improvements in axial involvement and pain.