Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Anifrolumab In Refractory Systemic Lupus Erythematosus: A Real-Life, Multicenter Study.

OBJECTIVE: To report the real-world experience on the use of ANI in refractory SLE. METHODS: Multicenter retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in active adult SLE patients in whom all the available treatment choices failed, were not tolerated or contraindicated.At baseline, at 1, 3, 6, 9 and 12 months of treatment, overall and organ specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in SLEDAI-2K (p=0.005), SLEDAS (p=0.005) and PGA (p=0.001) was recorded, and the same trend was maintained over time. A significant reduction in CLASI-activity (p<0.001) and in tender (p=0.026) and swollen (p=0.017) joint count was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, while 46% were in LLDAS; at 6 months, 50% were in remission and 80% in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (p=0.04). A total of 4 disease flares according to the SELENA-SLEDAI Flare Index were recorded (three mild-moderate and one severe). Overall, 4 out of 20 patients with at least 24 weeks of follow-up (20%) were considered "non responders". CONCLUSION: This study provides a real-world experience on the use of ANI in refractory SLE patients, confirming its rapid effectiveness and an overall acceptable safety profile.

Application of SLE-DAS to assess subcutaneous belimumab efficacy in a cohort of systemic lupus erythematosus patients.

OBJECTIVES: To assess the efficacy of subcutaneous (sc) belimumab (BLM) by the application of SLE-DAS in a monocentric SLE cohort. METHODS: We evaluated SLE patients treated with sc BLM from March 2019. Disease activity has been assessed by SLEDAI-2k, SLE-DAS and PGA (Physician Global Assessment) in all the established time-points [baseline (T0), after 1 (T1), 3 (T3), 6 (T6) and 12 (T12) months]. Furthermore, we applied and compared the achievement of remission according to SLE-DAS values (SLEDAS ≤2.08 + PDN ≤5mg/daily) and DORIS definition (clinical SLEDAI- 2k=0 + PGA<0.5 + antimalarial treatment, PDN≤5mg/daily, stable immunosuppressive treatment). RESULTS: We enrolled 86 patients [M/F 5/81, median age 48 years (IQR 17.5), median disease duration 166 months (IQR 216)]. At baseline, median values of SLEDA-2k and SLE-DAS were 6 (IQR 4) and 5.77 (IQR 4.33), respectively, and they significantly correlated (r=0.719, CI 95% 0.586-0.815, p<0.0001). Median duration of treatment was 14 months (IQR 20). We found a significant reduction of SLEDAI-2k and SLE-DAS already at T1, maintained in the subsequent time-points (p<0.0001). At T12, a remission state was achieved by 60.4% of patients according to SLE-DAS definition and by 62.3% according to the DORIS definition. Both definitions of remission have demonstrated an agreement of 84%, with a Cohen's kappa equal to 0.6. CONCLUSIONS: In this study we applied SLE-DAS to assess the efficacy of sc BLM, by analysing its over-time changes and by comparing its performance with SLEDAI-2k. Indeed, our results suggest the usefulness of this new activity index in a real-life setting.

Validation of Qualisex questionnaire to evaluate sexual dysfunction in women affected by fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) may have consequences on sexual life. The objective was to validate the Qualisex questionnaire in the assessment of sexual dysfunction in women affected by FM. METHODS: We consecutively enrolled FM women (American College of Rheumatology-ACR 2016) referring to our Fibromyalgia Clinic, from 2020 to 2022. Demographic, clinical data and evaluation of FM symptoms severity (Revised Fibromyalgia Impact Questionnaire (R-FIQ), Symptoms Severity Scale-SSS, Widespread Pain Index-WPI) were assessed. Hospital Anxiety and Depression Scale (HADS) and Qualisex questionnaire were anonymously administered. Qualisex includes 10 questions on different items of sexual life with higher scores suggestive of greater negative impact of the disease on sexuality. RESULTS: The cohort was composed by 373 FM women. Cronbach's alpha test was used to validate Qualisex questionnaire (0.878). Moreover, we observed higher values of Qualisex in married women (p<0.001), in women with lower grade of education (p=0.002) and with lower sexual feeling with partner (p<0.001). Higher values of Qualisex Total score showed a positive correlation with HADS-A/D (p<0.001 r=0.312; p<0.001 r=0.542 respectively), VAS pain, VAS fatigue, VAS dryness (p<0.001 r=0,438; p<0.001 r=0.375; p<0.001 r=0.370 respectively) and relationship duration (p<0.001 r=0.202). Multivariate analysis revealed a significant influence of relationship duration, VAS pain, fatigue, dryness, HADS-A/D, R-FIQ and all Qualisex items, on Qualisex Total score corrected for patients' age (p<0.001). CONCLUSIONS: This study validated Qualisex questionnaire as a good test for the sexual disorders' evaluation in FM women. Its use allows the assessment of different factors associated with sexual dysfunction, showing an impact of FM on sexuality. Moreover, due to demotivation feelings, sexual dysfunction contributes to worsen patients' quality of life.

Effectiveness and safety of filgotinib in rheumatoid arthritis patients: data from the GISEA registry.

OBJECTIVES: The aim of this study was to evaluate the effectiveness and safety profile of filgotinib, a JAK1 preferential inhibitor, in rheumatoid arthritis (RA) patients included in Italian GISEA (Group for the Study of Early Arthritis) registry. METHODS: Data from RA patients treated with filgotinib, recorded in the GISEA registry, were analysed. Disease activity scores and patient-reported outcomes (PROs) were assessed at baseline, as well as during 12-month follow-up. A difficult-to-treat (D2T) RA patient was defined according with EULAR criteria. Retention rate of filgotinib was estimated by the Kaplan-Meier method and factors influencing drug discontinuation were estimated by Cox regression models. RESULTS: 246 RA patients (female 89%, 57.6±12.2 years old) started filgotinib, mostly as second (22%) or further (43.9%) b/tsDMARDs line of treatment. At 3 and 12 months, 18.8% and 27.5% of patients achieved Clinical Diseases Activity Index based remission and 30.1% and 37.7% obtained a visual analogue scale of pain ≤20 (all p<0.01 vs. baseline). Filgotinib survival rate was 84.5% at the 6-month and 75.8% at 12-month follow-up, and was comparable either in monotherapy or combination therapy, and irrespective of glucocorticoid intake. b/tsDMARD naive patients had the lowest hazard ratio (HR) of filgotinib discontinuation (HR 0.29, 95%CI 0.14-0.64), while D2T-RA the highest (HR 1.82, 95%CI 1.01-3.3). Eight patients (3.3%) discontinued filgotinib due to adverse events. CONCLUSIONS: In an Italian real-life setting, filgotinib is confirmed to be safe and with a good effectiveness profile both in monotherapy and without glucocorticoids.

Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. METHODS: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. RESULTS: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. CONCLUSIONS: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Lung ultrasound compared to computed tomography detection and automated quantification of systemic sclerosis-associated interstitial lung disease: preliminary study.

Lung ultrasound (LUS) is a promising tool for detecting systemic sclerosis-associated interstitial lung disease (SSc-ILD). Currently, consensus on the best LUS findings and execution technique is lacking. OBJECTIVES: To compare qualitative and quantitative assessment of B-lines and pleural line (PL) alterations in SSc-ILD with chest computed tomography (CT) analysis. METHODS: During 2021-2022, consecutive SSc patients according to 2013 ACR/EULAR classification criteria underwent pulmonary functional tests (PFTs). On the same day, if a CT was performed over a ± 6 months period, LUS was performed by two certified blinded operators using a 14-scans method. The ≥10 B-lines cut-off proposed by Tardella and the Fairchild's PL criteria fulfilment were selected as qualitative findings. As quantitative assessment, total B-lines number and the quantitative PL score adapted from the semi-quantitative Pinal-Fernandez score were collected. CT scans were evaluated by two thoracic radiologists for ILD presence, with further processing by automated texture analysis software (qCT). RESULTS: 29 SSc patients were enrolled. Both qualitative LUS scores were significantly associated to ILD presence on CT, with Fairchild's PL criteria resulting in slightly more accuracy. Results were confirmed on multivariate analysis. All qualitative and quantitative LUS findings were found to be significantly associated with qCT ILD extension and radiological abnormalities. Mid and basal PL quantitative score correlated with mid and basal qCT ILD extents. Both B-lines and PL alterations differently correlated with PFTs and clinical variables. CONCLUSION: This preliminary study suggests the utility of a comprehensive LUS assessment for SSc-ILD detection compared with CT and qCT.

Citrullinated and carbamylated proteins in extracellular microvesicles from plasma of patients with rheumatoid arthritis.

OBJECTIVES: To investigate the expression of citrullinated and carbamylated proteins in extracellular microvesicles (EMVs) from RA patients. METHODS: We enrolled 24 RA naïve for biological therapy and 20 healthy donors (HD), matched for age and sex. For each patient, laboratory and clinical data were recorded and clinical indexes were measured (Clinical Disease Activity Index, Simplified Disease Activity Index, DAS28). EMVs in RA patients and HD were purified from plasma and measured by nanoparticle tracking analysis (NanoSight). Further, EMVs were incubated with anti-citrullinated/carbamylated proteins antibodies and processed by flow cytometry and western blot to evaluate the expression of citrullinated/carbamylated antigens. RESULTS: NanoSight revealed a significant increase of EMVs in RA compared with HD. Moreover, cytofluorimetric analysis showed a significative higher expression of citrullinated antigens on EMVs' surface in RA than donors, while no substantial difference was found in the expression of carbamylated antigens. These data were confirmed by western blot which identified vimentin, glycolytic enzyme alpha-enolase 1 and collagen type II as the main citrullinated and carbamylated proteins carried by EMVs. Finally, a relevant correlation between the expression of citrullinated antigens and disease activity was found. CONCLUSIONS: The results of this study suggest an involvement of EMVs in the pathogenesis of RA by inducing autoimmunity.

Fragility fractures in lupus patients: Associated factors and comparison of four fracture risk assessment tools.

OBJECTIVE: Osteoporosis (OP) and fragility fractures (FF) are common comorbidities in patients with systemic lupus erythematosus (SLE). This study aimed to (1) assess the prevalence of these conditions in a cohort of SLE patients (2) evaluate the risk factors associated with FF, and (3) compare the accuracy of four different FF risk assessment algorithms to determine which performs better in this specific rheumatologic population. MATERIALS AND METHODS: We conducted a cross-sectional study with SLE women who underwent bone mineral density assessment by dual-energy X-ray absorptiometry (DEXA) within 3 months of their last visit. Conventional radiology methods were used to evaluate the presence of FF. The 10-year risk of osteoporotic fractures was estimated using four tools: DeFRA, FRAX (adjusted for GC dosage), GARVAN, and QFracture. The comparison of these computational tools was analyzed by the area under the receiver operating characteristic (ROC) curves. RESULTS: We analyzed 86 SLE patients with a median age of 56 years (IQR 12.1) and a median age at diagnosis of 34 years (IQR 17.2). The median T-score values at the femoral neck and lumbar spine were -1.6 (IQR 0.9) and -1.7 (IQR 1.1), respectively. Of the patients, 33 (38.4%) had OP, with 13 patients (15.1%) experiencing FF. Univariate analysis showed that the presence of FF was associated with thrombocytopenia (p = .01), hemolytic anemia (p = .0001), and the intake of cyclosporine A (p = .002), cyclophosphamide (p = .006), and rituximab (p = .001). The median 10-year risk of major FF for the four calculation tools were as follows: DeFRA 9.85 (IQR 8.6); FRAX GC 8.8 (IQR11.7); GARVAN 12 (IQR 8.2); QFracture 4.1 (IQR 5.8). We observed a significant correlation among all instruments evaluated (p < .0001); in particular, the best correlation was recorded between the FRAX GC and the DeFRA (r = 0.85). DeFRA was the best tool for this population with an AUC of 0.94 (p < .0001, CI 0.88-1). CONCLUSIONS: OP is a common comorbidity in SLE patients, even in younger patients. FF appears to be more frequent in patients with hematologic involvement. The comparison of the four algorithms shows that DeFRA is the most accurate tool and should be applied to SLE patients.

KLRG1 is reduced on NK cells in SLE patients, inversely correlates with disease activity and is modulated by hydroxychloroquine in vitro.

OBJECTIVES: Killer cell lectin-like receptor G 1 (KLRG1), a transmembrane receptor with inhibitory capacity expressed in human immune cells, emerged as a novel susceptibility gene for systemic lupus erythematosus (SLE). The aim of this study was to investigate the expression of KLRG1 in SLE patients compared to healthy controls (HC) on both NK and T cells and to evaluate its possible involvement in SLE pathogenesis. METHODS: Eighteen SLE patients and twelve healthy controls were enrolled. Peripheral blood mononuclear cells (PBMCs) from these patients were phenotypically characterized by immunofluorescence and flow cytometry. The effect of the hydroxychloroquine (HCQ) in vitro on KLRG1 expression and its signaling mediated functions in NK cells were analyzed. RESULTS: KLRG1 expression was significantly reduced on the analyzed immune cell populations in SLE patients compared to HC, especially on total NK cells. Moreover, expression of KLRG1 on total NK cells inversely correlated with the SLEDAI-2K. A direct association between KLRG1 expression on NK cells and patients' treatment with HCQ was observed. In vitro treatment with HCQ increased KLRG1 expression on NK cells. In HC, KLRG1+ NK cells showed reduced degranulation and IFNγ production, while in SLE patient, this inhibition occurred only for the IFNγ production. CONCLUSION: With this study we revealed a reduced expression and an impaired function of KLRG1 on NK cells in SLE patients. These results suggest a possible role of KLRG1 in the pathogenesis of SLE and as a novel biomarker of this disease.

Evidence of immune response to BNT162b2 COVID-19 vaccine in systemic lupus erythematosus patients treated with Belimumab.

OBJECTIVES: To evaluate humoral and cell-mediated response after three doses of BNT162b2 SARS-CoV-2 vaccine in patients with systemic lupus erythematosus (SLE) treated with Belimumab (BLM). METHODS: SLE patients were vaccinated with three doses of BNT162b2-mRNA vaccine (two-dose primary vaccination, third booster dose after 6 months). The humoral immune response was assessed one and 6 months after the second dose (T1, T2), and 6 months after the booster dose (T3). Serological assay was performed (The Liaison® SARS-CoV-2 TrimericS IgG chemiluminescent). Spike-specific T-cell response was monitored 6 months after the second vaccine dose and the percentage of cytokines producing T cells was assessed by flow cytometry. RESULTS: Twelve patients [12F; median age 46 years (IQR 8.25); median disease duration 156 months (IQR 188)] were enrolled. At T1, all patients showed seroconversion (median anti-Spike IgG levels 1610 BAU/mL, IQR 1390). At T2--day of the third dose--a significant reduction of median anti-Spike IgG antibodies levels was observed [214 BAU/mL (IQR 94); p = 0.0009]. Anti-Spike IgG were significantly increased at T3, reaching a median value of 1440 BAU/mL (IQR 1316; p = 0.005). Despite declining humoral immunity, almost 60% of patients mounted a virus-specific CD4 + T-cell response 6 months after primary vaccination. CONCLUSIONS: BLM does not impair humoral response to primary BNT162b2 SARS-CoV-2 vaccination. During the follow-up, a decline in antibody levels is evident and the third dose is crucial to increase the specific immune response. Finally, we observed a recall T-cell response to the Spike antigen 6 months after the first vaccination cycle.

Gender differences in the revised Fibromyalgia Impact Questionnaire: a pilot study.

OBJECTIVES: Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with symptoms such as fatigue, sleep disturbances and cognitive impairment. Prevalence is higher in females but the application of the 2010/2011 and 2016 revision of the American College of Rheumatology (ACR) criteria reduced prevalence differences and the actual female:male ratio is approximately 3:1. Even if lately some studies have been conducted regarding FM gender differences, disease severity is still assessed using questionnaires, such as the Revised Fibromyalgia Impact Questionnaire (FIQR), designed and validated through a predominantly female sample. The aim of this pilot study was to compare the 21 items of the FIQR among male and female patients in order to evaluate the possible existence of a gender bias. METHODS: In this case-control study, consecutive patients with a diagnosis of FM (2016 ACR criteria) were asked to answer an online survey, including demographic characteristics, disease variables and the Italian version of the FIQR. Among the 544 patients that compiled the questionnaire, 78 patients, 39 males and 39 females, matched for age and disease duration, were consecutively enrolled in order to compare their FIQR scores. RESULTS: The univariate analysis showed that total FIQR scores and physical function domain scores were significantly higher in females and, among the 21 items of the FIQR, the female group obtained significantly higher scores in 6 of them. Our results showed that female patients obtain significantly higher scores in the FIQR total score and physical function domain score, in particular in 5 out of the 9 sub-items of the FIQR physical function domain. CONCLUSIONS: These preliminary results indicate that the use of the FIQR as a severity index in male patients probably underestimates the disease impact in this group.

Effectiveness of non-medical switch from adalimumab bio-originator to SB5 biosimilar and from ABP501 adalimumab biosimilar to SB5 biosimilar in patients with chronic inflammatory arthropathies: a monocentric observational study.

OBJECTIVES: The use of biosimilars is constantly growing, prompting healthcare payers to encourage the switch to these drugs which are less expensive than the reference bio-originator. While switching from a bio-originator to a biosimilar is supported by increasing evidence, data on the switch between different biosimilars of the same reference product are scant. Our study aimed to evaluate the effectiveness of the non-medical switch both between adalimumab (ADA) bio-originator and SB5 biosimilar and between two different ADA biosimilars in patients with inflammatory chronic arthritis. METHODS: We observed adult patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) treated with ADA bio-originator or ABP501 ADA biosimilar (Amgevita) who switched to SB5 ADA biosimilar (Imraldi) for administrative/economic reasons. Patients were followed up for 4 months. RESULTS: One hundred and ten patients [33 RA, 40 PsA, 37 axSpA; F:M= 49:61; median age 56 years (25th-75th percentile 48-66)] switched from ADA bio-originator to SB5. After 4 months (T4), we observed a significant reduction of patients in remission/low disease activity (baseline 92.7% vs. T4 80.9%; p=0.009), with a risk of moderate-high disease activity significantly higher after the switch [RR 2.6 (95% IC 1.2 to 5.7), p=0.01]. However, no differences were found in DAS28-CRP, DAPSA, ASDAS-CRP, and BASDAI, while patients with RA and PsA experienced a worsening in the patient global assessment-VAS (p=0.04 and p=0.02, respectively), and in patients with PsA a worsening in HAQ was also observed (p=0.03). Forty patients switched from ABP501 biosimilar to SB5 [12 with RA, 25 with PsA, and 3 with axSpA; F:M=24:16; median age 56 years (25th-75th percentile 44-66)]. After 4 months, no differences in DAS28-CRP and DAPSA nor in the percentage of patients in remission/low disease activity were found compared to baseline. Likewise, no differences were found in patient-reported outcomes (PROs). CONCLUSIONS: Our results provide a reassuring profile of effectiveness when switching from ADA originator to one of its biosimilars and between two different biosimilars. However, the worse outcome in PROs in patients initially treated with the bio-originator addresses the attention to a possible nocebo response, which should encourage comprehensive communication with patients.

Adherence to therapy in people with rheumatic and musculoskeletal diseases in Italy and the role of the digital health: results of an expert Delphi consensus survey.

OBJECTIVES: To present the results of a Delphi consensus survey among Italian rheumatologists on adherence to therapy in people with rheumatic and musculoskeletal diseases (RMDs) in Italy and the role of digital health. METHODS: A taskforce of 12 rheumatologists comprehensively discussed the applicability of the 2020 EULAR Points to Consider (PtCs) for Italian rheumatology practice and formulated 44 new country-specific statements. Through an on-line survey, the panellists voted on their level of agreement with the statements using a 10-point Likert scale (0: no agreement; 10: total agreement). A combination of two distinct criteria, a mean agreement level ≥8 and a percentage of at least 75% of responses with a value ≥8, was deemed acceptable. RESULTS: The consensus threshold was reached for 43 of the 44 country-specific statements. The following were acknowledged among the barriers to applicability of the recommendations: visit time too short; lack of resources; lack of a clear operational flow-chart; lack of communication skills and poor knowledge of techniques to improve patient adherence by healthcare professionals (HCPs). CONCLUSIONS: This consensus initiative helps contribute to more widespread implementation of EULAR PtCs in Italian rheumatology practice. Optimisation of visit time, greater availability of resources, specific training, use of standardised and validated protocols, and active involvement of patients represent the main goals. Digital health can provide valuable support for the application of PtCs and, more generally, in improving adherence. A collaborative effort between HCPs, patients and their associations, scientific societies, and policymakers is strongly advocated to overcome some of the barriers.

Multicentre case-control study evaluating the safety of anti-SARS-CoV-2 vaccines in a cohort of patients with systemic vasculitis.

OBJECTIVES: Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS: Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS: 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS: These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

Persistence, effectiveness and safety of ustekinumab compared to TNF inhibitors in psoriatic arthritis within the Italian PsABio cohort.

OBJECTIVES: To compare real-world persistence, effectiveness and tolerability of ustekinumab versus TNF inhibitors (TNFi) in psoriatic arthritis (PsA). METHODS: One-year data from Italian subjects enrolled in the PsABio study (PsA patients receiving 1st- to 3rd-line treatment with ustekinumab or TNFi) were evaluated. Treatment persistence was analysed using Kaplan-Meier curves; hazard ratios (HR) of stopping treatment, and the corresponding 95% confidence intervals (CI), were computed through Cox regression models. Proportions of patients reaching clinical effectiveness endpoints were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation if treatment was stopped/switched. RESULTS: Among 222 participants with follow-up data (effectiveness set), 101 received ustekinumab and 121 TNFi. In the ustekinumab group, 74.3% continued treatment up to 12±3 months compared to 63.6% in the TNFi group. Ustekinumab showed better persistence than TNFi, overall and in specific subgroups (females, monotherapy without methotrexate, BMI <25 or >30 kg/m2, patients receiving ustekinumab as 2nd-line treatment instead of a second TNFi). Overall, the PS-adjusted HR of treatment discontinuation was 0.46 (95% CI: 0.26-0.82) for ustekinumab vs. TNFi. cDAPSA LDA/remission was achieved in 43.5% of ustekinumab and 43.6% of TNFi-treated patients, while MDA was achieved in 24.2% and 28.0% of patients, respectively. After PS adjustment, odds ratios of clinical effectiveness did not differ significantly. Both treatments showed an acceptable safety profile. CONCLUSIONS: This prospective, real-life study found a better persistence of ustekinumab than TNFi in PsA patients. At 1 year, both treatments showed similar effectiveness.

Similarities and differences between younger and older disease onset patients with newly diagnosed systemic lupus erythematosus.

OBJECTIVES: Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. METHODS: We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18-45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. RESULTS: Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18-45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. CONCLUSIONS: In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.

Clinical and histological features of patients with primary Sjögren's syndrome and autoimmune thyroiditis: a national multicentre cross-sectional study.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of patients with pSS and associated AT. METHODS: In this multicentre cross-sectional study, data from 2546 pSS were collected and the presence of AT was reported. In a subgroup, the histology of minor salivary glands was evaluated. Differences between pSS with and without AT were evaluated. RESULTS: A concomitant pSS and AT was detected in 19.6% of cases. Patients with pSS and AT displayed a lower prevalence of lymphoma, male sex and disease-modifying anti-rheumatic drugs (DMARDs) use and a higher prevalence of fibromyalgia, coeliac disease and hypergammaglobulinaemia. Multivariable analysis confirmed a higher prevalence of fibromyalgia and coeliac disease and lower use of DMARDs. In a subgroup of patients (n=232), a significantly higher focus score and number of foci was detected in pSS without AT (n=169) as compared to pSS with AT (n=54). CONCLUSIONS: This is the largest study evaluating the coexistence of pSS and AT. We confirm a high association between pSS and AT and describe the presence of a different phenotype characterized by a higher rate of celiac disease and fibromyalgia. Although not significant, the lower prevalence of both lymphoma and intake of DMARDs, along with a significantly lower focus score and number of foci, possibly suggest a more favourable outcome in concomitant pSS and AT which further deserve future investigations.