Background. The safety of biologic immunosuppressants in systemic lupus erythematosus (SLE) has been demonstrated in several interventional studies. However, estimates from unselected, real-world clinical populations remain scarce. This study aims to assess the safety of biologic immunosuppressants used as monotherapy (MONO-BIS) or in combination (COMB-BIS), compared to the exclusive use of non-biologic immunosuppressants (NBIS), in patients with SLE starting a new immunosuppressive treatment. Materials and Methods. LIRE is a prospective, multicentre, pharmacoepidemiologic observational study promoted by the Italian Society of Rheumatology (SIR) (full list of investigators: https://redcap.reumatologia.it/surveys/?s=LWL7WJM4KHDR97CC). SLE patients who started a new immunosuppressive therapy between 2015 and 2022 were followed every six months for up to 5 years. Adverse events (AEs) were classified according to CTCAE v4.0 criteria and categorized as serious adverse events (SAEs), infections (INF), adverse events of special interest (AESI: infections, neoplasms, cardiovascular events), hospitalizations (HOSP), and deaths (DEA). Incidence rates and relative risks of AEs were estimated using weighted Cox models adjusted for baseline treatment indication. In addition to demographic factors, estimates were adjusted for anti-DNA antibody positivity, organ involvement (SLEDAI and/or BILAG), disease damage (SLICC-DI), disease activity (SLEDAI-2K), concomitant hydroxychloroquine use, and cumulative steroid dose (>10 g). Results. Among the 338 included patients (87% women), 179 started NBIS, 55 MONO-BIS, and 104 COMB-BIS therapy. Belimumab (39%), rituximab (7%), mycophenolate (31%), and methotrexate (21%) were the most frequently used immunosuppressants. Infections were more frequent among BIS users (40%) compared to NBIS (18%), with higher rates in COMB-BIS (42%) than in MONO-BIS (35%). The COMB-BIS group had a higher prevalence of lupus nephritis (46%), higher cumulative corticosteroid exposure (>10 g prednisone equivalent: 58%), and a longer mean disease duration (12.6 years). The COMB-BIS group showed a significantly higher risk of AEs compared with NBIS (HR [95% CI]: 1.90 [1.29–2.79]), while the MONO-BIS group showed a non-significant increase (1.35 [0.76–2.40]). The risk of infections was significantly higher in COMB-BIS (2.82 [1.41–5.63]), and higher but not significantly so in MONO-BIS (2.49 [0.85–7.29]). Conclusions. In this Italian real-world study, biologic drugs were associated with a higher risk of AEs when used in combination with NBIS, particularly infections occurring in the first months after treatment initiation. However, no relevant differences were found in serious adverse events (SAEs) or mortality within 24 months. These findings highlight that in patients with multi-organ involvement, the use of combined immunosuppressive therapy should be carefully evaluated and personalized according to individual clinical profiles, to balance therapeutic efficacy and the risk of adverse events.

Background. Vasoactive-vasodilating drugs (VVD) are the cornerstone of the treatment of pulmonary arterial hypertension (PAH), a form of precapillary pulmonary hypertension (pPH) that represents a complication of systemic sclerosis (SSc). VVD categories include endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5i) and prostanoids, which are commonly used to treat digital ulcers (DU) and Raynaud’s phenomenon. As protective effects remain unclear, we investigated the effectiveness of VVD on the primary prevention of pPH. Materials and Methods. SSc patients from the EUSTAR cohort who underwent right heart catheterization (RHC) were included; postcapillary PH cases (pulmonary wedge pressure – PWP >15 mmHg) were excluded. Multivariable logistic regression assessed the association between exposure to VVD and detection of pPH (mPAP>20 mmHg, PVR>2 WU and PWP<15 mmHg) and of PAH (pPH, ILD extent <20% and FVC >70%). Models 1 and 2 tested the exposure at the time of RHC ever and ongoing to VVD categories, models 3 and 4 tested the same for specific VVD molecules. The primary outcome was the diagnosis of precapillary PH; PAH was analyzed as sensitivity analyses. All models were adjusted for known confounders. Interaction terms between VVDs and current DU were also tested. Results. Among 944 eligible patients, 498 (53%) were diagnosed with pPH, of whom 367 (74%) had PAH (Table 1). For VVD classes, a statistically significant association was detected for the interaction of ERAs and current DU with the detection of pPH, in both logistic regression models 1 and 2 (Figure 1a and 1b). However, this finally resulted in a non-significant association between ERAs exposure in patients with current DU and PH detection when calculating marginal effects estimates (ERAs ongoing: OR 0.435, 95%CI 0.193-1.064; ERAs ever: OR 0.636, 95%CI 0.349-1.158). Additionally, both models showed lack of effectiveness of ERAs in patients without current DU, as well as for PDE5i or prostanoids overall. When focusing on specific VVD molecules, exposure “ever” to bosentan showed a significant protective association with pPH diagnosis, independently from the presence or absence of current DU (Figure 1c). Finally, we noted a statistically significant interaction between ongoing bosentan and current DU, which turned into a significant marginal effects estimate (OR 0.230, 95% CI 0.081 – 0.652) indicating protective effects of this medication towards the diagnosis of pPH in patients with current DU (Figure 1d). The protective effects of bosentan were confirmed in all sensitivity analyses targeting PAH detection. Conclusions. Our data show that bosentan is associated with less frequent diagnosis of PAH and precapillary PH, in particular when employed in patients with current DU at the time of RHC. Our results support further research to optimize the timing and patient selection for VVD therapy in SSc, aiming also at additional preventive effects at pulmonary level.

Background/Purpose: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with high morbidity and mortality. Accurate and early diagnosis of SSc-PAH is essential to initiate targeted therapies that may improve outcomes by counteracting key pathophysiological mechanisms. Breathomics, the analysis of volatile organic compounds (VOCs) in exhaled breath, has emerged as a promising non-invasive tool, as VOCs reflect underlying metabolic and pathological processes. This study investigates the potential of breathomics in SSc-PAH, both for disease understanding and diagnosis. Methods: 14 SSc patients with a diagnosis of PAH confirmed by right heart catheterization, 28 age- and sex-matched SSc patients without PAH, and 36 matched healthy controls (HCs) were enrolled in a single-center, case-control observational study. Exhaled breath VOCs were collected using the ReCIVA® breath sampler connected to a clean air supply (CASPER®). Samples were trapped on sorbent tubes and analyzed by thermal desorption gas chromatography–mass spectrometry (TD-GC-MS) at Owlstone Medical. VOCs were chemically identified according to Metabolomics Standards Initiative (MSI) criteria, and blank air samples were analyzed to distinguish true breath compounds from environmental contaminants. Data were analyzed using linear regression, adjusting for relevant covariates and excluding outliers. Results: all SSc participants were female and predominantly affected by lcSSc (n = 23, 63.4%) and mostly tested positive for ACA (n = 40, 85%). The mean age was 68 ± 9 years, with no differences between the SSc-PAH and SSc-noPAH groups. A total of 1.382 VOCs were analyzed; of these, 186 were confirmed to be genuinely present “on breath” and annotated with high confidence (MSI tier 1 or 2). Among these, 55 VOCs significantly differentiated SSc-PAH from SSc-noPAH, and 40 differentiated SSc-PAH from healthy controls. Notably, 32 VOCs distinguished SSc-PAH from both comparator groups (p < 0.05 and |fold change| > 1.5) (Figure 1). Findings of interest included: a reduction in terpenes in SSc-PAH, potentially reflecting impaired vasodilatory capacity (Figure 2); a decrease in sulfur-containing compounds, suggestive of reduced control over vasoconstriction; a reduction end-products (i.e. 1-pentene) of allyl organosulfur derivates with anti-inflammatory properties; an increase in pyrazines, possibly indicative of enhanced gut permeability; and elevated levels of the uremic toxin m-cresol, which has been associated with endothelial dysfunction. Conclusions: breathomics revealed a distinct metabolic signature in SSc-PAH, distinguishing it from both SSc without PAH and healthy controls. The identified VOCs not only hold promise as non-invasive biomarkers for early diagnosis but also shed light on key pathogenic mechanisms of PAH, including impaired vasoregulation, increased gut permeability, and endothelial dysfunction. These findings support the role of breath analysis as a valuable tool for both clinical and mechanistic insights in SSc-PAH.

Background. Lupus low disease activity state (LLDAS) and remission are key therapeutic targets in systemic lupus erythematosus (SLE), associated with better long-term outcomes. This study aimed to evaluate the frequency of LLDAS achievement 12 months after an extra-renal flare and to identify clinical and serological predictors in a monocentric SLE cohort. Methods. This observational cohort study included SLE patients with an extra-renal disease flare between 2017 and 2024. Patients were assessed at the flare occurrence (T0) then at 3 (T3), 6 (T6), and 12 months (T12). Active organ involvement at flare was categorized based on BILAG domains, and disease activity at T0 and follow-up was evaluated by SLEDAI-2K score. At each time point, the attainment of clinical remission (based on the DORIS definition, excluding the physician global assessment [PGA]) and/or LLDAS-5 (according to modified criteria: excluding the PGA and requiring a prednisone dose < = 5 mg/day) was recorded. Univariate and multivariable logistic regression analysis of potential predictors were performed. Results. 98 patients were included. Demographic, clinical, and therapeutic characteristics are summarized in Table 1. During the follow-up, SLEDAI-2K score progressively declined from a median of 7 (4-10) to 2 (0-4); at 12 months, 67 (69.0%) patients were in LLDAS5 and 38 (38.7%) were in remission. As shown in figure 1, clinical outcomes assessed at 3, 6, and 12 months demonstrated a gradual increase in the proportion of patients achieving LLDAS5 and clinical remission. Comparison between those who reached LLDAS-5 at T12 and those who did not is detailed in Table 2. Patients not achieving LLDAS-T12 received significantly higher cumulative 6-methylprednisolone doses (2786.2 ± 349.6 mg vs 1740.3 ± 158.8 mg, p = 0.002) and higher daily doses at T12 (7.07 ± 1.38 mg/day vs 2.95 ± 0.24 mg/day, p < 0.001). In univariate analysis, variables associated with the achievement of LLDAS5 at 12 months resulted: SLEDAI-2k score at flare (7.4 ± 5.5, p < 0.005), male sex (93.3% vs. 64.6%, p = 0.027), the presence of anti-dsDNA antibodies at flare (p = 0.014). However, in multivariable logistic regression, only the baseline SLEDAI score remained significantly associated with LLDAS5 at 12 months (OR 0.89, 95% CI 0.82–0.97). An additional key finding is that no specific BILAG domain manifestation was independently associated with the achievement of LLDAS5 at T12; however, hematologic (OR 0.15, p= 0.015) and mucocutaneous involvement (OR 0.29, p= 0.018) were both negatively associated with remission at T12. Conclusions. This study demonstrated that in real-life setting, achievement of treatment targets with standard of care remains suboptimal, especially in patients with high disease activity, mucocutaneous and hematological manifestations. Interestingly, patients not achieving targets required significantly higher doses of 6-MP, highlighting the importance of early disease control and tailored treatment strategies.

Background. The aim of this study is to analyze, in a cohort of patients with chronic inflammatory arthropathy, the correlation between ultrasonographic parameters and the Krenn Synovitis Score (KSS) – a validated semi-quantitative scale for the histological classification of synovitis, used to evaluate the degree of synovial inflammation. Materials and Methods. We included patients aged ≥18 years with a diagnosis of RA, according to the 2010 ACR/EULAR classification criteria, or PsA, according to the CASPAR criteria, were recruited. Eligible participants were required to be candidates for initiation or modification of DMARD therapy and to have complete ultrasonographic data at baseline, defined as a polyarticular assessment using the Global OMERACT–EULAR Synovitis Score (GLOESS) and ultrasound evaluation of the biopsy site. Each patient underwent an ultrasound-guided synovial biopsy of a clinically involved joint (knee or wrist). Synovial tissue specimens were evaluated by an experienced pathologist to determine the KSS. Statistical analyses were conducted using Spearman’s rank correlation coefficient, a non-parametric measure of association. Results. A total of 63 patients were evaluated (58 with RA and 5 with PsA). Among them, 92% (58/63) had failed at least one csDMARD, and 51% (32/63) had failed at least one b/tsDMARD. The mean (SD) polyarticular GLOESS value was 15 (12), while the median (IQR) KSS was 6 (4.00, 6.00) (Table 1). GLOESS (rho = 0.23, p = 0.013), gray-scale (GS) intensity (rho = 0.35, p < 0.001), and the degree of joint effusion (rho = 0.27, p = 0.004) at the biopsy site showed a positive correlation with the KSS (Figure 1). Regarding the KSS sub-items, a positive correlation was observed between all ultrasound variables and the degree of inflammatory infiltrate on histological examination (rho = 0.38, p < 0.001 for GS; rho = 0.30, p = 0.002 for effusion; rho = 0.23, p = 0.014 for PD). No statistically significant correlation was found between Power Doppler (PD) signal intensity of the examined joint and the overall KSS (rho = 0.16, p = 0.1), lining score (rho = 0.10, p = 0.3), or stroma score (rho = –0.05, p = 0.6). Conclusions. In the examined patient cohort, a positive correlation was observed between the polyarticular GLOESS score and the KSS, as well as between ultrasonographic parameters at the biopsy site and the degree of inflammatory infiltrate on histological assessment. Moreover, only specific ultrasound variables such as gray-scale intensity and the extent of joint effusion at the biopsy site showed a positive correlation with KSS, whereas no such correlation was confirmed for the Power Doppler (PD) signal. These findings, together with the rho values indicating a weak correlation, suggest that synovitis is influenced by factors not fully identifiable through ultrasound assessment alone, supporting the role of KSS and synovial biopsy as valuable tools for a more accurate characterization of chronic inflammatory arthropathies.

Background. Idiopathic inflammatory myopathies (IIM) are a group of rare and heterogeneous diseases. One of the greatest challenges in IIM management is defining and predicting disease flares, which are inconsistently characterized across studies. The aim of the study was to identify predictors of relapse in a retro-prospective, multi-centric IIM cohort during the first two years of disease. Methods. Patients with IIM subsets—dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), connective tissue disease-associated IIM (CTD-IIM), or immune-mediated necrotizing myopathy (IMNM)—were included if >=18 yrs and with >= 2 years of follow-up. Relapse was defined as a change in disease activity requiring escalation of immunosuppressive therapy and/or steroids. Patients were classified as monocyclic (no relapse in the first 2 years), polycyclic (>=1 relapse in the first 2 years), or chronic continuous. Clinical characteristics across subgroups were compared using chi-square, Mann–Whitney U, or Student’s t-test. Predictors were identified through multivariable logistic regression. Results. Of 297 screened patients, 91 were excluded due to missing data. A total of 206 patients were included (155 female; median age at diagnosis 46.9 years). 82 (39.8%) were DM, 56 (27.2%) ASyS, 40 (19.4%) CTD-IIM, 14 (6.8%) PM, and 14 (6.8%) IMNM. During the first 2 years of disease, 84 patients (40.8%) had monocyclic course, 67 (32.5%) polycyclic course, and 55 (26.7%) chronic continuous course. No significant differences in disease course distribution were observed across IIM subsets, although PM and IMNM were more frequently associated with chronic or relapsing patterns (64.2% vs. 35.8%). Myositis autoantibodies were not significantly linked to any disease course. Relapses occurred despite stable treatment for over one year in approximately one-third of cases. Most relapses involved muscle (61.9%), particularly in PM/IMNM (89%), whereas the frequency was notably lower in ASyS (43.2%), where ILD was the leading cause of relapse (61.4%). Refractory disease was the predominant phenotype in PM/IMNM (55.6%) and ASyS (52.3%), while drug tapering was most frequent cause implicated in DM (30%) and CTD-IIM (31%). Muscle and cardiac involvement at baseline were less frequent in monocyclic patients. A more severe disease phenotype—reflected by higher levels of muscle enzymes, and both PtGA and PhGA—was more commonly associated with non-monocyclic disease. Notably, non-monocyclic patients had received baseline low-dose steroids (<0.25 mg/kg; 78.9% vs. 21.1%, p = 0.019) and intravenous immunoglobulins (10.0% vs. 26.0%, p = 0.004). Multivariable analysis confirmed baseline muscle involvement, CK levels, and PtGA as independent predictors of relapse. - Conclusions. In this large, diverse IIM cohort, non-monocyclic disease (polycyclic and chronic continuous) was associated with baseline myositis, higher serum muscle enzymes, higher global activity scores, and lower steroid induction dosage. These findings highlight the potential value of flare predictors and advocate for standardized definitions of disease activity/relapse in IIM.

Background. Our study endeavoured to investigate the real-life use of immunosuppressants after cancer diagnosis in patients with spondyloarthritis (SpA) and rheumatoid arthritis (RA) and the associated risk of cancer recurrence or mortality. Methods. We retrospectively enrolled all patients with invasive cancer and SpA, psoriatic arthritis (PsA) or RA referred to two Italian centres between 2015 and 2024. Invasive cancer was defined as any solid or haematologic cancer with histological characteristics of invasiveness. Cancer recurrence or progression were recorded consulting oncologic reports. After correction for the immortal bias, we performed a survival analysis using a model with cumulative incidence for competing events and subdistribution hazard ratios (SHR) estimates. Results. Overall, we included 120 patients with SpA/RA (39 SpA, 37 PsA, 44 RA) who developed invasive cancer. Most patients were undergoing csDMARDs and bDMARDs treatment before cancer diagnosis, or initiated immunosuppressants (including TNF, IL-6, IL-17, IL-23, JAK inhibitors and CTLA4a) after cancer diagnosis. 24 (20%) patients experienced a cancer relapse or progression, of whom 7 subsequently died. 2 other patients died of other causes during follow-up. Treatment with bDMARDs/JAKi before and after cancer did not appear to significantly increase the risk of recurrence and/or death (SHR p-value = 0.26; SHR p-value= 0.78), after correction for treatment before cancer diagnosis. RA was significantly associated with a higher risk of recurrence (SHR p-value <0.05). Early introduction of bDMARDs, particularly in RA, increased the risk of recurrence/death (HR p-value <0.05). Conclusion. The management of patients with SpA and RA who develop cancer may require initiation of immunosuppressants before the 5-year safety cutoff in the most severe cases. Among biologics, IL6i, IL17i and IL23i have proven to be the safest classes for use in patients with rheumatic diseases who develop cancer (1,2). 1. Atzeni F, Carletto A, Foti R, et al. Incidence of cancer in patients with spondyloarthritis treated with anti-TNF drugs. Joint Bone Spine. 2018;85(4):455-459. doi:10.1016/j.jbspin.2017.08.003 2. Scagnellato L, Collesei A, Doria A, et al. Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs. Clin Exp Rheumatol. Published online February 8, 2023. doi:10.55563/clinexprheumatol/q38lu0

Background. Eosinophilic gastrointestinal disorders are characterized by marked eosinophilic infiltration of the gastrointestinal (GI) tract causing organ dysfunction and the onset of GI symptoms. They may present in isolation or as part of systemic diseases including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Mepolizumab (MEPO), an anti-interleukin-5 monoclonal antibody, is approved for both conditions; however, data are limited regarding its effectiveness in managing GI involvement. This study aims to evaluate MEPO’s effectiveness on EGPA and HES-related GI involvement. Materials and Methods. This was a retrospective cohort study conducted among centres referring to the European EGPA Study Group. Inclusion criteria: age >18 years; EGPA or HES diagnosis; GI manifestations confirmed by histology or imaging; start of MEPO any dosage (100 or 300 mg/month sc, 750 mg/month iv) for uncontrolled GI manifestations. Data were collected from disease onset until MEPO start (t0), at 1 (t1), 3 (t3), 6 (t6), 12 (t12), 24 (t24) months, and during flares (exacerbations of GI symptoms requiring therapeutic escalation). Outcomes included symptom improvement, absolute eosinophil count (AEC) reduction, flare occurrence, and corticosteroid (CS)-sparing effect. Data are presented as n (%) or median (IQR). Wilcoxon or McNemar tests were used as appropriate. Flare rates (flares/patient-month) pre- and post-MEPO were compared using incidence rate ratio (IRR) with 95% CI (p<.05). Results. Forty-eight patients were included. At baseline, all the patients had active GI involvement, with median peak AEC 3857 (1593-9743) cells/mm3. Forty-six patients (96%) had a history of CS use prior to MEPO. Median time from diagnosis to MEPO start was 5 (1-49) months (Table 1). Median AEC decreased by t1 [t0: 805 (482-1805) cells/mm3; t1: 115 (60–223); p<.001] and remained low through t24 [70 (23–108) cells/mm3; p<.001]. By t24, active GI symptoms decreased from 65% to 12% (p<.001) and oral CS (OCS) use from 85% to 46% (p=.001). Median prednisone-equivalent daily dose decreased from 11.3 (5-25) mg/day at t0 to 0 (0-2.5) mg/day at t24 (p<.001) (Table 2). During follow up, 8 patients experienced a GI relapse. All of them were on a stable MEPO dose, with 3 also using OCS (2 tapering) and 1 MMF. Only 1 case of increased AEC was documented. All flares were managed by adjusting CS therapy; MEPO dose was increased from 100 mg to 300 mg/month in 2 cases and immunosuppressive therapy was added in 2 others (Table 3). The flare rate decreased from 0.021 to 0.0049 flares per patient-month after MEPO (IRR 0.23, 95% CI 0.11–0.49, p=.0001), indicating 77% reduction in flare incidence. Conclusions. MEPO effectively controlled GI symptoms in EGPA and HES patients and reduced CS use.

Background. Women with systemic lupus erythematosus (SLE), especially those treated with immunosuppressants, have a greater risk of developing cervical cancer related to the human papilloma virus (HPV). Vaccination against HPV and screening for early detection of HPV are safe and effective prevention measures. The objectives of this study are to evaluate vaccine coverage and adherence to the HPV infection screening programs in women with LES, as well as investigate the incidence of infection in these patients. Methods. A cross-sectional study was conducted by administering an anonymous survey on vaccination and infection screening adherence to consecutive SLE patients attending our center's Lupus Clinic. Data on HPV infection and HPV vaccination in women were analyzed. Results. From March to June 2025, 45 women with SLE completed the survey (Table 1). Among these patients, 67% (30/45) expressed uncertainty regarding the safety of vaccines for patients with SLE, while 60% (27/45) reported not knowing which vaccinations are recommended. Regarding HPV vaccination coverage, only 3/45 (6.7%) reported having been vaccinated against HPV, while the majority (33/45, 73.3%) reported not having been vaccinated: 58% (19/33) of unvaccinated patients were in treatment with glucocorticoids (GCs), 82% (27/33) with conventional disease-modifying antirheumatic drugs (cDMARDs), and 27% (9/33) with biological disease-modifying antirheumatic drugs (bDMARDs). Figure 1 describes the reasons that led patients not to undergo vaccination. The main barriers were the lack of recommendation by the doctor (19/33, 56.7%) and lack of information about the vaccine (9/33, 27.3%). 27/45 patients (60%) reported regularly undergoing PAP tests or HPV DNA tests, while 12 (26.7%) declared they did not. Finally, 5/45 patients (11.1%) reported having been diagnosed with HPV infection. Conclusions. In our study, HPV vaccination coverage was suboptimal in patients with SLE, and the lack of promotion and information about the vaccine was the main barrier. Adherence to screening for early HPV diagnosis was also suboptimal. This underscores the importance of the referring specialist's role in providing information and promoting adherence, in order to improve the level of prevention in these patients.

We aim to estimate the incidence of IBD-SpA in a population of Crohn’s disease (CD) patients and to identify risk factors associated with the development of IBD-SpA. This retrospective observational cohort study included all consecutive patients with a CD diagnosis followed by our IBD outpatient clinic who underwent at least one magnetic resonance enterography (MRE) between 2011 and 2023. Patients without a full scan of sacroiliac joints (SIJs) on MRE, having other rheumatic diseases, diagnosed with SpA before CD diagnosis, missing key clinical or imaging data, death or lost to follow-up at the time of data collection, were excluded. The identification of new onset IBD-SpA during the follow-up was based on the fulfillment of the ASAS classification criteria. Baseline demographic and clinical data, and immunosuppressive therapies performed were collected. Presence of articular and intestinal lesions at MRE was established according to the most recent definitions by ASAS and the Society of Abdominal Radiology, respectively. Incidence rates were calculated as the number of new cases of SpA divided by the total person-time at risk, expressed per 1,000 person-years. Log-rank test and univariate Cox proportional hazards regression analyses were performed to estimate hazard ratios (HR) for categorical and continuous predictors. A total of 147 CD patients [M:F 1:1, median age (IQR) 46.3 (23.3) years, median CD duration (IQR) was of 4.50 (16.4) years] were selected. Descriptive statistics of the sample are shown in Table 1. The incidence rates of overall, axial, and peripheral IBD-SpA were 3.8, 2.1, and 1.7 cases per 1,000 person-year, respectively. A stricturing CD behavior (HR: 0.22; 95% CI: 0.05–0.93; p=0.040), baseline mesalazine treatment (HR: 0.24; 95% CI: 0.06–0.99; p=0.049), greater age (HR: 0.94; 95% CI: 0.89–1.00; p=0.035), and CD duration (HR: 0.84; 95% CI: 0.72–0.97; p=0.019), were associated with a reduced risk of developing IBD-arthritis. The sub-analysis conducted for each subset of arthritis revealed an increased risk of axial IBD-SpA for active sacroiliitis (HR 6.08; 95% CI 1.11-33.4; p=0.038), and ankylosis of SIJs on MRE (HR 47.7; 95% CI 2.99-763.4; p=0.006), while revealed a reduced risk for baseline mesalazine treatment (HR 0.20; 95% CI 0.04-1.11; p=0.067), greater age (HR: 0.93; 95% CI: 0.86–1.00; p=0.040) and CD duration (HR: 0.84; 95% CI: 0.71–0.99; p=0.033). An increased risk of peripheral IBD-SpA emerged only for ankylosis of SIJs (HR 24.6; 95% CI 2.23-271.8; p=0.009). A reduced incidence rate of IBD-SpA was associated with a stricturing CD behavior, baseline mesalazine treatment, increasing age and CD duration. Active sacroiliitis at baseline MRE was associated with the development of axial IBD-SpA; mesalazine therapy, greater age and CD duration were protective factors. Table 1: descriptive statistics of the sample.