Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group.

Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study.

Background: Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP). Methods: We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6 months. Results: Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change. Conclusion: Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.

Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: An analysis on a nation-wide database.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis. METHODS: We conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk. RESULTS: We found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18-1.49 and 2.43, 95 % CI 2.17-2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively). CONCLUSION: Some glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.

Long-term effectiveness and predictors of bisphosphonate treatment in type I complex regional pain syndrome.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. Bisphosphonates are largely used in the real-life for the treatment of CRPS, but data on long-term effectiveness and its predictors are lacking. METHODS: We conducted a longitudinal observational study on patients with type I CRPS treated with IV neridronate (100 mg on 4 occasions). Clinical and demographic characteristics were collected at baseline, after 3 months (M3) and after 12 months (M12). Multivariable logistic regression was employed to determine the factors associated with long-term response to treatment. RESULTS: 103 patients with type I CRPS treated with IV neridronate were included in the study. Mean VAS pain at baseline was 79.1 mm and decreased significantly at M3 (-45.9 mm, 95% CI 40.1 to 51.8) and M12 (-61.6 mm, 95% CI 55.3 to 67.9). Hyperalgesia and allodynia resolved in 84.3% and 88.1% of patients at M12. Loss of motion resolved in 53.5% of patients. The predictors of excellent response were gender (male better), predisposing event to CRPS (no event being better than any predisposing event), site of CRPS (lower limb being better), and early response at M3 on VAS pain (2.5 times the chance of being excellent responder every 10 mm decrease). CONCLUSIONS: In this real-life study neridronate was associated with rapid and progressive improvement of symptoms of CRPS which was maintained up to 3 years of follow-up. The predictors of excellent response were early response, lower limb localisation, absence of predisposing events and male gender.

Machine learning to characterize bone biomarkers profile in rheumatoid arthritis.

Background: Bone metabolism is disrupted in rheumatoid arthritis (RA); however, the bone metabolic signature of RA is poorly known. The objective of the study is to further characterize the bone metabolic profile of RA and compare it to psoriatic arthritis (PsA), systemic sclerosis (SSc) and healthy controls. Methods: We did a cross-sectional case-control study on consecutively enrolled patients and age-matched controls. We collected clinical characteristics, serum biomarkers related to bone metabolism and Bone Mineral Density (BMD). A multiple correlation analysis using Spearman's rank correlation coefficient was conducted within the RA patient group to investigate associations between biomarker levels and clinical variables. Machine learning (ML) models and Principal Component Analysis (PCA) was performed to evaluate the ability of bone biomarker profiles to differentiate RA patients from controls. Results: We found significantly lower BMD in RA patients compared to PsA, and Systemic Sclerosis SSc groups. RA patients exhibited higher Dkk1, sclerostin and lower P1nP and B-ALP levels compared to controls. No significant differences in CTX levels were noted. Correlation analysis revealed associations between bone biomarkers and clinical variables. PCA and ML highlighted distinct biomarker patterns in RA which can effectively discriminated bone biomarkers profile in RA from controls. Conclusion: Our study helped uncover the distinct bone profile in RA, including changes in bone density and unique biomarker patterns. These findings enhance our comprehension of the intricate links between inflammation, bone dynamics, and RA activity, offering potential insights for diagnostic and therapeutic advancements in managing bone involvement in this challenging condition.

Effects of cytotoxic T-lymphocyte-associated protein 4 compared to TNF inhibitors on lipid profile: Results from an observational multicentre rheumatoid arthritis cohort.

AIM: To evaluate the impact of selective cytotoxic T-lymphocyte-associated protein 4 (CTLA-4Ig) compared to tumor necrosis factor inhibitors (TNFi) on cardiovascular (CV) clinical and laboratory outcomes in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational multicenter study of RA patients included in the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group database, collecting demographic, clinical, and laboratory data of those starting a CTLA-4Ig or TNFi at baseline, 6-month, and 12-month follow-up. RESULTS: Of the 206 RA patients without previous CV events enrolled in the study, 64 received a CTLA-4Ig and 142 a TNFi. The two groups did not differ in age, gender, or smoking habits, and the prevalence of hypertension, diabetes, and metabolic syndrome was similar. Over a follow-up period of 12 months, although no significant differences were found in the disease activity course, we observed that LDL cholesterol levels slightly decreased only in the CTLA-4Ig-treated patients. CONCLUSIONS: Patients treated with both CTLA-4Ig and TNFi did not differ in disease activity response and changes in traditional CV risk factors after 12 months of treatment. However, CTL-A-4Ig treatment is associated with a favorable change in lipid profile at 12-month follow-up.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.

Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs).

Background: Biological DMARDs (bDMARDs) have been proven to prevent joint damage and bone erosions. Nevertheless, approximately 15% of rheumatoid arthritis (RA) patients on bDMARDs will progress despite good control of joint inflammation. Objectives: The objective of our study is to investigate the factors associated with radiological progression of patients treated with bDMARDs. Design: We conducted a retrospective analysis of longitudinally collected data on RA patients starting bDMARDs. Methods: Presence or development of new erosions was assessed by a skilled rheumatologist at the time of the visit (baseline and 12 months thereafter). To determine the predictors of erosions, we employed multivariable logistic regression models. Discriminatory capacity for the prediction of new erosion development was assessed with receiver operating characteristic (ROC) curve, which was based on the logistic regression model. Results: A total of 578 RA patients starting bDMARDs were included in the study. Overall, 46 patients (approximately 10%) had radiographic progression (at least one new erosion) at 12 months of follow-up. The factors independently associated with higher risk of developing new erosions while on bDMARD were younger age, high disease activity at baseline, not being treated with cDMARDs, and presenting with erosions at baseline. In addition, we built a predictive model that can accurately foresee new erosions (AUC 0.846) in patients receiving bDMARDs. Conclusion: We found that baseline erosive disease, higher disease activity during treatment, younger age, and monotherapy were the factors independently associated with the development of bone erosions. Our study may inform future targeted intervention in RA patients at risk of radiographic progression.

Changes in bone turnover markers and bone modulators during abatacept treatment.

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference - 0.17 95% CI - 0.42 to - 0.10, p 0.001 and - 0.09 95% CI - 0.23 to - 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference - 0.019 g/cm2 95% CI - 0.036 to - 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

A patient-driven registry on Behçet's disease: the AIDA for patients pilot project.

Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.

Ultrasonographic non-radiographic erosions could predict the efficacy of belimumab in articular systemic lupus erythematosus.

The aim of this study is to characterise lupus-related arthritis and assess if the presence of ultrasound-detected erosions could be associated with belimumab in the treatment of systemic lupus erythematosus (SLE) articular manifestations. We performed a spontaneous, monocentric, retrospective, and observational study. We enrolled patients affected by SLE with articular involvement treated with belimumab. We excluded patients with positive rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA), Jaccoud's arthropathy, and radiographic erosions. Patients were assessed at baseline, 3, and 6 months. We collected laboratory and clinical data from electronic records. Joint disease activity was assessed using disease activity score on 28 joints based on C-reactive protein (DAS28-CRP), swollen and tender joints count. All patients underwent an ultrasound examination of the wrist, metacarpophalangeal, proximal interphalangeal, and metatarsal-phalangeal joints before the initiation of treatment with belimumab. We performed Student's T-test and Mann-Whitney's U-test to assess the difference between means and Fisher's exact test to assess difference in proportions, and linear univariate regression to investigate predictors of disease activity. We enrolled 23 patients (female 82.6%, mean age of 50.65 ± 14.1 years). Seven patients (30.4%) presented bone erosions at baseline. Patients with bone erosions were generally older (61 ± 16.1 vs 46.13 ± 10.7 years, p = 0.016), more frequently male (42.8 vs 6.2%, p = 0.03), with higher baseline CRP levels (10.29 ± 11.6 vs 2.25 ± 3.1 mg/L, p = 0.015) and C4 levels (0.19 ± 0.17 vs 0.1 ± 0.04 g/L, p = 0.05). After 6 months of treatment with belimumab, patients without erosions improved their DAS28-CRP significantly (2.95 ± 0.89 vs 2.26 ± 0.48, p = 0.01), while patients with erosions did not (3.6 ± 0.79 vs 3.2 ± 0.95, p = 0.413). DAS28-CRP did not differ between the two groups at baseline, while it was significantly lower at the other two time points in patients without erosions. The majority of patients achieved remission at 6 months follow-up based on DAS28-CRP criteria (73.9%), with a significant difference between patients with and without erosions (42.8 vs 87.5%, p = 0.045). The presence of articular ultrasound-detected erosions could be predictive of a decreased efficacy of belimumab in the articular manifestations of SLE. A possible explanation is a rheumatoid-like articular phenotype, despite the lack of ACPA-positivity and radiologic erosions. However, due to the small sample population, larger cohorts are needed to assess the possible predictive role of this finding.

Bone Loss in Inflammatory Rheumatic Musculoskeletal Disease Patients Treated With Low-Dose Glucocorticoids and Prevention by Anti-Osteoporosis Medications.

OBJECTIVE: The negative effects of glucocorticoids on bone depend on dose and treatment duration. However, it is unclear whether a safe dose exists, especially for patients with inflammatory rheumatic musculoskeletal diseases (iRMDs). We undertook this study to determine the effects of glucocorticoid doses on bone health in iRMD patients. METHODS: We conducted a longitudinal cohort study on women with iRMD. Bone mineral density (BMD) and fractures were assessed prospectively and compared to a matched cohort without iRMD. Kaplan-Meier curves with log rank test were made for iRMD patients (stratified for glucocorticoid use and dose) and the matched cohort. Multivariable Cox regression survival models were also employed to analyze the effect of glucocorticoids on fracture. RESULTS: A total of 884 women with iRMD and 1,766 controls (matched for age, T score, and 10-year fracture risk) were included in the study and followed up for up to 6 years. BMD decreased significantly in all patients receiving glucocorticoids who were not receiving anti-osteoporosis treatment (-4.26% for ≥5 mg/day of prednisone equivalent, P = 0.0011; -4.23% for 2.5-5 mg/day, P = 0.0422; -2.66% for 0-2.5 mg/day, P = 0.0006). Anti-osteoporosis treatment (largely bisphosphonates) prevented bone loss only in patients receiving <5 mg/day of prednisone equivalent. Fracture incidence was higher in patients with iRMD compared to controls, but only glucocorticoid doses ≥5 mg/day were associated with significantly higher risk of fracture. CONCLUSION: Glucocorticoid doses as low as 2.5 mg/day were associated with BMD loss in iRMD patients, but this effect was preventable. BMD loss in patients receiving ≥5 mg/day was not totally prevented by anti-osteoporosis medications currently used in clinical practice, resulting in higher risk of fracture.

Italian recommendations for the assessment of cardiovascular risk in rheumatoid arthritis: a position paper of the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group of the Italian Society for Rheumatology.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events. The aim of this position paper is to provide Italian rheumatologists with an easy, feasible and time-saving CV risk assessment in their daily clinical practice. METHODS: A narrative review of the literature and an assessment of the methodological strength underlying the current evidence on CV risk assessment in patients with RA were performed. The evidence-based results were shared among the members of the steering committee of the CORDIS study group of the Italian Society of Rheumatology. Subsequently, a unanimously agreed-upon algorithm was discussed and finally approved by the experts. RESULTS: RA patients should have their CV profile monitored using the Italian 'Progetto Cuore' chart, according to the current EULAR recommendations for CV risk management, at least every 5 years. In the presence of high disease activity, or a multi-drug failure condition, when prolonged treatment with glucocorticoids and/or NSAIDs is required, or if hypertension, dyslipidaemia, or diabetes mellitus are concomitant, a more stringent CV risk assessment should be considered. When moderate CV risk is documented, patients should undergo intima-media thickening measurement. The condition of high CV risk requires a cardiological evaluation. CONCLUSIONS: This position paper provides five Italian recommendations for CV risk assessment in RA patients. A general and uniform approach to CV risk profiling may be useful to identify those patients who should undertake intensive preventive strategies to improve their CV outcomes.

Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients.

Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs).

INTRODUCTION: Glucocorticoids are still a mainstream of rheumatoid arthritis (RA) treatment. Reducing glucocorticoids should be attempted in all patients. However, choosing the right tapering strategy is challenging. The primary aim of our study is to determine the dose-response association between glucocorticoid tapering and risk of flare in RA. METHODS: We conducted a case-crossover study to determine the factors associated to higher risk of flare in patients with RA. In case-crossover studies time-varying factors are assessed before events (hazard periods) and before control periods. We defined hazard periods as the 6 months immediately preceding flares of RA. Control periods were the 6 months prior to visits without flare. Exposure of interest was the tapering of glucocorticoids to various doses. RESULTS: 508 patients with RA were included in the study and 267 (52.5%) had at least a flare and served as the case-crossover study population. 1545 visits were available for analysis and 345 (22.3%) flares were recorded. Discontinuation of glucocorticoids (ie, tapering to doses of 0 mg/day) and tapering to 0-2.5 mg/day was associated with higher risk of flare (adjusted OR (aOR) of 1.45, 95% CI: 1.13 to 2.24 and aOR of 1.37; 95% CI: 1.06 to 2.01, respectively). Tapering to doses >2.5 mg/day was not associated with significantly higher risk of flare. CONCLUSIONS: We found that tapering to doses of >2.5 mg/day was generally effective in terms of risk of flare. Flare risk was higher when glucocorticoids were tapered to doses ≤2.5 mg/day. Our study might help design new tapering strategies in patients with RA on biological disease-modifying antirheumatic drugs.

Radiofrequency echographic multi-spectrometry and DXA for the evaluation of bone mineral density in a peritoneal dialysis setting.

BACKGROUND: The aim of this real-life cross-sectional explorative study was to compare radiofrequency echographic multi-spectrometry (REMS) with dual-energy X-rays absorptiometry (DXA) in the BMD assessment of patients receiving peritoneal dialysis (PD). Furthermore, we investigated the relationship between lumbar aortic calcifications (AOCs) and the DXA lumbar measurements. METHODS: Consecutive patients referring to the PD clinic of our hospital were included. Lumbar spine and femur scans were acquired with both techniques (including lumbar laterolateral DXA scans). The risk assessment of two fracture risk algorithms (FRAX® and DeFRA®) were compared. Cohen's k coefficients were used to assess the inter-technique agreement in the classification of patients as osteoporotic. Lumbar AOCs were estimated semi-quantitatively on laterolateral DXA scans. RESULTS: 41 patients were enrolled. No significant differences were documented between the BMD T-scores measured through DXA or REMS at the femur. At the lumbar spine, the DXA anteroposterior mean T-score (- 0.49 ± 1.98) was significantly higher than both the laterolateral DXA (- 1.66 ± 0.99) and the REMS (- 2.00 ± 1.94) measurements (p < 0.01 vs both). No significant differences were found between the DXA and REMS fracture risk estimates with both algorithms. The inter-technique Cohen's k coefficient (for the worst T-score, any site) was 0.421, p < 0.001. The discrepancy between the DXA laterolateral and anteroposterior lumbar T-score was positively associated with the AOCs extent and severity (r = 0.402, p < 0.01). CONCLUSIONS: Our data showed a promising agreement, in a real-life PD setting, between DXA and REMS BMD assessment and in the consequent fracture risk estimation and confirm the AOCs interference on the diagnostic accuracy of lumbar DXA.