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The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.
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Fertilidade , Infertilidade Feminina , Espondilartrite , Humanos , Feminino , Espondilartrite/tratamento farmacológico , Gravidez , Infertilidade Feminina/etiologia , Adulto , Reserva OvarianaRESUMO
Objectives: This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). Methods: Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded. Results: We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex. Conclusions: Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.
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Anticorpos Monoclonais Humanizados , Espondiloartrite Axial , Humanos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Itália , Adulto , Resultado do Tratamento , Espondiloartrite Axial/tratamento farmacológico , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Estudos Prospectivos , Estudos de CoortesRESUMO
Background/Objectives: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis (OA) and a severely disabling condition. Patients affected by OA frequently lament symptoms suggestive of neuropathic pain (NP). The aim of our study was to ascertain the presence and severity of NP in patients with EHOA and correlate its presence with EHOA clinical characteristics. Methods: In this retrospective study, we included all consecutive EHOA patients with NP symptoms who underwent upper limb electroneurography (ENoG) and nerve ultrasound. The presence of NP was screened using the ID pain neuropathic pain-screening questionnaire (ID-Pain). In addition, the following NP questionnaires were also used: Douleur Neuropathique en 4 Questions (DN4), PainDETECT, and Neuropathic Pain Symptom Inventory (NPSI). Moreover, patients completed the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Dreiser's algofunctional finger index questionnaires assessing EHOA disease activity. The following clinical and laboratory data were collected: age, sex, BMI, disease duration, intensity of pain (VAS 0-10), painful and swollen joints, and inflammatory indices, as well as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Of the 34 patients studied, 24 (70.6%) presented NP to the ID-Pain questionnaire. According to DN4, 14 (41.2%) patients had NP, while using the PainDETECT questionnaire, 67.6% had NP. Patients with NP were statistically younger and had a higher VAS pain score compared to subjects without NP. The ENoG and median nerve ultrasound were normal in 81% of patients, while four patients had carpal tunnel syndrome. The ID-Pain questionnaire correlated with the number of painful joints (r = 0.48, p = 0.03) and with the AUSCAN questionnaire (r = 0.37, p = 0.05). The DN4 questionnaire correlated with PainDETECT (r = 0.58, p < 0.01). The PainDETECT questionnaire correlated with VAS pain (r = 0.49, p = 0.02), the DN4 questionnaire (r = 0.58, p < 0.01), and AUSCAN (r = 0.51, p = 0.02). The NPSI questionnaire correlated negatively with BMI (r = -0.53, p = 0.01) and positively with the PainDETECT questionnaire (r = 0.49, p = 0.02). Conclusions: Our study revealed that 32% to 70% of EHOA patients exhibited symptoms consistent with NP, with observed variability depending on the questionnaire utilized. Despite patients frequently exhibiting symptoms compatible with NP, only 19% of patients presented alterations on ENoG and ultrasound examinations confirming CTS. This suggests a probable nociplastic component for pain in patients with EHOA, which warrants tailored treatment. In the present study, NP correlated with clinical and functional indices of EHOA.
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INTRODUCTION: Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. METHODS: We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. RESULTS: Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. CONCLUSION: In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.
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Antirreumáticos , Artrite Juvenil , Recidiva , Humanos , Artrite Juvenil/tratamento farmacológico , Adulto , Masculino , Feminino , Adulto Jovem , Adolescente , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
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.
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Antirreumáticos , Fibromialgia , Neoplasias , Espondilartrite , Humanos , Antirreumáticos/uso terapêutico , Comorbidade , Fibromialgia/epidemiologia , Neoplasias/epidemiologia , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêuticoRESUMO
Objectives: To investigate the effects of SARS-CoV-2 infection, as well as short- (within 48 hours) and long-term (within 30 days) adverse events (AEs) of SARS-CoV-2 vaccines, including arthritis flares in a large cohort of patients with inflammatory arthritis (IA). Methods: A retrospective cohort study comprising 362 patients: 94 (26%) rheumatoid arthritis, 158 (43.6%) psoriatic arthritis and 110 (30.4%) ankylosing spondylitis; and 165 healthy controls (HC) to ascertain the prevalence and severity of SARS-CoV-2 infection in patients with IA, the rate of AEs associated with SARS-CoV-2 vaccines and disease flares within a month of the vaccination. All patients provided informed consent and data about SARS-CoV-2 infection and/or vaccination status. Results: One-hundred-seventeen (32.3%) patients and 39 (23.6%) HC were affected by SARS-CoV-2 infection. Forty (34.2%) patients experienced an IA flare within one month of infection, of whom 3 (7.5%) needed to switch therapy. The prevalence of SARS-CoV-2 infection, disease severity, and hospitalization rate were not significantly different. At least one shot of SARS-CoV-2 vaccine was administered in 331 (91.4%) patients and 147 (89.1%) HC. Within 48 hours, 102 (30.8%) patients developed vaccine-related AEs; 52 (15.7%) patients with >1 vaccine dose experienced an IA flare-up, of whom 12 (23.1%) needed to switch therapy. Conclusions: A significantly higher rate of IA flare was observed among patients who contracted SARS-CoV-2 infection vs. those without infection. Patients with IA experienced flares after SARS-CoV-2 vaccination, though it was not statistically significant.
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OBJECTIVE: (1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to examine frequency and predictors of low disease activity (LDA) in patients with axial involvement (axPsA). METHODS: consecutive PsA patients in stable biological/targeted-synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs/tDMARDs) who attended our center were enrolled. Disease activity indices, including MDA and ankylosing spondylitis disease activity score-LDA (ASDAS-LDA) for axPsA, were evaluated at baseline and every 6 months, up to 36 months or bDMARDs/tsDMARDs discontinuation. Patients' history, BMI, comorbidities - including osteoarthritis (OA) and fibromyalgia - were collected. Variables were compared between patients who achieved sustained MDA and those who did not. Multivariable generalized estimating equation (GEE) models were built to identify predictors of MDA and ASDAS-LDA over time. Data were expressed as beta coefficient (95%CI). RESULTS: 104 patients were enrolled, 54% males, mean age 55.7 years; 52% had axPsA. Across all evaluations, 52-61% reached MDA, and 17-24% achieved ASDAS-LDA. AxPsA, fibromyalgia, OA and BMI≥35 were less frequently observed in patients with sustained MDA. The GEE model confirmed the following factors were significantly and independently associated with MDA: age (Beta=-0.05), bDMARDs/tsDMARDs duration (Beta=+0.31), axPsA (Beta=-1.07), fibromyalgia (Beta=-3.35), OA (Beta=-1.87), BMI≥35 (Beta=-2.53). Age (Beta=-0.01), fibromyalgia (Beta=-2.03) and OA (Beta=-1.30) were also independently associated with ASDAS-LDA. CONCLUSIONS: MDA is an attainable target in real-life. AxPsA represents a difficult-to-treat subset. Sustained MDA depends on disease features (axPsA) as well as patients' characteristics (e.g. age, bDMARDs/tDMARDs duration, comorbidities).
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Antirreumáticos , Artrite Psoriásica , Fibromialgia , Osteoartrite , Espondilite Anquilosante , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/complicações , Fibromialgia/tratamento farmacológico , Fibromialgia/complicações , Antirreumáticos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Comorbidade , Osteoartrite/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient's subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA-IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4ß7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA-IBD.
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Produtos Biológicos , Doenças Inflamatórias Intestinais , Espondilartrite , Humanos , Qualidade de Vida , Espondilartrite/complicações , Doenças Inflamatórias Intestinais/complicações , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
Cytophagocytic mononuclear (CPM) cells, previously known as Reiter's cells, are macrophages containing apoptotic polymorphonuclear leucocytes. Although they can be found in synovial fluid (SF) from different arthropathies, their role remains unclear. This study was performed to determine the frequency and disease distribution of CPM cells in SF in a large cohort of patients with rheumatic diseases over a 12-year period. We also investigated the seasonal variation in their incidence. This record review study included the reports pertaining to SF analyses performed between January 2010 and December 2021. Data were retrieved from the charts of inpatients and outpatients at Rheumatology and Emergency Departments of Padova. The total number of SF samples containing CPM cells was 189: 69% was from patients with seronegative spondyloarthritis (SpA), thus indicating a strong association between CPM cells and SpA. SF samples containing CPM cells were predominantly inflammatory. Our analyses demonstrated a 6-month cyclical fluctuation in concentrations of CPM cells, with an increase in spring and autumn. The presence of CPM cells in SF might offer diagnostic insight into the definition of SpA. Further studies are warranted to ascertain the link between CPM cells and the apoptotic process, shedding light on the mechanisms leading to their formation.
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Neutrófilos , Líquido Sinovial , Humanos , Estações do Ano , Macrófagos , ApoptoseRESUMO
Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8-18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7-215.9) vs. 239.9 (217.9-286.9), respectively, p < 0.001) and at T24 (207.6 (182.5-246.5) vs. 261.1 (210.2-286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (ß -0.5, p < 0.001) and at T24 (ß -0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage.
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Espondiloartrite Axial , Sacroileíte , Espondilartrite , Feminino , Humanos , Masculino , alfa-2-Glicoproteína-HS , alfa-Fetoproteínas , Biomarcadores , Estudos de Coortes , Imageamento por Ressonância Magnética/métodos , Articulação Sacroilíaca , Sacroileíte/complicações , Sacroileíte/diagnóstico , Espondilartrite/diagnósticoRESUMO
OBJECTIVES: Our study aimed to systematically review the evidence about the effect of diet or dietary supplements on spondyloarthritis (SpA) disease activity. METHODS: a systematic literature review (SLR) was conducted in MEDLINE, EMBASE, Cochrane and SCOPUS according to the "PEO" format (Population, Exposure, Outcome). The population was SpA (axial or peripheral, axSpA/pSpA, including Psoriatic Arthritis-PsA); the intervention any kind of diet/dietary supplement; the outcome disease activity. Inclusion criteria were: adult patients, Randomized Controlled Trials (RCTs) and longitudinal studies (so that a pre-and post-intervention assessment were available), papers in English. Risk of bias (RoB) was conducted with different tools according to the design of the study. RESULTS: Literature search yielded 1390 publications, of which 15 were finally inlcuded: 12 interventional and 3 observational studies. Among those with the lower RoB: a) 2 RCTs, one at unclear and one at low RoB, failed to show benefit of probiotics in SpA b) Two RCTs at unclear RoB provided evidence that weight loss, but not hypocaloric diet, was associated to MDA achievement in PsA. The remaining interventional studies were at high RoB. Among the observational studies, one study on Mediterranean diet demonstrated an association between diet adherence and a ≥ 20% decrease of ASDAS in axSpA. The other two observational studies were judged of poor quality. CONCLUSIONS: weight loss seem to be able to impact disease activity in PsA, while probiotics do not seem useful in SpA; evidence for dietary behaviors is scarce and heterogeneous.
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Artrite Psoriásica , Espondilartrite , Adulto , Humanos , Dieta , Redução de PesoRESUMO
OBJECTIVES: Gout treatment is largely suboptimal in clinical practice. We aimed to assess the predictors of disease-activity at 12 months in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre-cohort study. Only patients with clinical diagnosis of gout were eligible. Disease-activity was evaluated by the Patient Acceptable Symptom State (PASS) on a visual analogue scale (VAS, 0=unsatisfactory, 100=satisfactory) at 0 (T0) and 12 months (T12), and the composite score called Gout Activity Score (GAS) calculated on the number of arthritic attacks (flare count), serum uric acid (sUA), cumulative number of tophi, VAS (T12), PtGA (T12). Multivariate linear regression model was performed to assess predictors of gout disease-activity at T12 with PASS and GAS as outcomes. RESULTS: 201 patients had gout (diagnosis on synovial fluid in 45%, tophi in 26%, mean sUA 7.4±1.9 mg/L, 85% with urate-lowering therapy (ULT) in progress/initiated at T0); mean age 63±13 years, 88% men, median (interquartile range) disease duration 2.9 years (0.7-9.4). Follow-up visits were performed in 113 (56%) patients at T12. Mean PASS observed at T0 and at T12 were 38±27 and 74±23, respectively, whereas GAS at T12 was 10±8. A significant association was observed between the presence of tophi and PASS at T12 (-15.3, 95% CI -25.5, -5.2; p=0.003) and GAS at T12 (+4.0, 95% CI 0.6,7.4; p=0.02), adjusted for age, sex, disease duration, sUA <6 mg/dL, tender joint count, PASS at T0, ULT). CONCLUSIONS: The baseline presence of tophi may predict high disease-activity at T12, thus worsening GAS and patients' pain perception.
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Gota , Ácido Úrico , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Supressores da Gota/efeitos adversos , Estudos de Coortes , Gota/diagnóstico , Gota/tratamento farmacológico , Modelos LinearesRESUMO
Psoriatic arthritis (PsA) is a multifaceted inflammatory disease associated with psoriasis that can affect peripheral joints, entheses, and the axial skeleton with a variable clinical course. Acute episodes of joint swelling in PsA patients can have different causes and require specific treatments. We aimed to describe the acute joint swelling in PsA patients via synovial fluid (SF) analyses, assessing in particular the presence of pathogenic crystals, to determine whether it is a flare or an acute episode of gout ("psout") during the course of the disease. This retrospective study was based on the results of SF analysis of samples collected from unselected adult PsA patients referred to our clinic for acute joint swelling. Demographic characteristics, disease involvement, laboratory findings on SF, and treatment options were recorded and reviewed. Among 5,478 SF samples analyzed in a 10-year time span, 213 complete SF records from PsA patients were evaluated. Overall, after adjustment for the degree of synovial inflammation, significant differences were observed in term of sex (p = 0.0017) and ongoing therapy (p = 0.0246). Non-inflammatory SFs, indeed, were mainly described for female PsA patients under therapy. Regarding serum uric acid levels, there were 19/213 (8.9%) PsA with hyperuricemia (HU), who were older, mostly male, patients with mild articular involvement and rare pathogenic crystals in their SF. Although it is known that the risk of gout is higher among patients with PsA ("psout"), monosodium urate crystals were reported only in 5/213 SFs (2.4%) of our cohort and in 2/19 SFs (10.5%) of HU PsA patients. Moreover, hyperuricemia seems not to modify the SF features in PsA patients. This study results seem to suggest that the convergence of gout and PsA, involving the role of urate crystals, is a more intricate relationship, which needs further insights to be unraveled.
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Artrite Psoriásica , Gota , Hiperuricemia , Adulto , Humanos , Masculino , Feminino , Líquido Sinovial/química , Artrite Psoriásica/complicações , Ácido Úrico/análise , Estudos RetrospectivosRESUMO
Objectives: To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)]. Methods: Consecutive axSpA patients treated with SEC were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical-values were recorded at baseline (T0), 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded. Results: A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9-4.4) versus T24 = 1.9 (1.2-2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0-7.5) versus T24 = 2.8 (1.8-4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender (p = 0.002). Conclusion: In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.
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STING (stimulator of interferon genes) has been recognized as an important signaling molecule in the innate immune response to cytosolic nucleic acids. Although it has been proposed that STING signaling pathway may play a pathogenic role in developing autoimmune and autoinflammatory diseases, its involvement in rheumatic disease processes remains to be elucidated. Here, we evaluated STING protein levels, expression and relationship with inflammatory parameters in synovial fluid (SF) of patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), gout, calcium pyrophosphate crystal-induced arthritis (CPP-IA), osteoarthritis (OA), and OA with CPP crystals (OA + CPP). The correlation with its negative regulator, nuclear factor erythroid 2-related factor 2 (Nrf2), was also investigated. SFs from 72 patients were analyzed for white blood cell (WBC) count, polymorphonuclear cell percentage (PMN%), and IL-1ß, IL-6, IL-8, extra- and intracellular STING levels. STING and Nrf2 expression was also determined. WBC count and PMN% were greater in SF from inflammatory arthritis, while they were lower in OA groups. RA and gouty SFs have the highest levels of IL-1ß, IL-8, and IL-6; while OA and OA + CPP showed the lowest concentrations. Gout and RA had the highest intracellular STING levels, while extracellular STING was greater in CPP-IA and OA SFs. STING was not detectable in PsA. STING mRNA was lower in PsA than other arthritides. Nrf2 mRNA was not detectable in OA. This study determines the presence of STING in SF of different arthritides, except for PsA, and suggests that it may be involved in pathogenesis and progression of arthropathies.
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Artrite Psoriásica , Artrite Reumatoide , Gota , Proteínas de Membrana , Osteoartrite , Artrite Psoriásica/metabolismo , Gota/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Osteoartrite/metabolismo , Líquido Sinovial/químicaRESUMO
BACKGROUND: Secukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether patients with arthritis may carry a risk factor for withdrawal. OBJECTIVE: To identify predictors of secukinumab survival, including the presence of arthritis, in PsO and PsA. METHODS: Consecutive PsO and PsA patients initiating secukinumab were enrolled and followed up every 6 months, up to 24 months or discontinuation. Medical history, disease activity indices and body mass index (BMI) were collected. Kaplan-Meier curves and log-rank test were used to analyze differences in drug survival according to sex, BMI, biological therapy line in the whole population (psoriatic disease), and separately for PsO/PsA. A multivariable Cox regression model was built to assess whether presence of arthritis (main independent variable) may influence drug survival by having time to secukinumab discontinuation as outcome. Results were expressed as hazard ratio and 95% confidence interval. RESULTS: Sixty-two PsO and 90 PsA patients were enrolled. Retention rate at 12 and 24 months, respectively, was 85% and 61% for PsO and 68% and 57% for PsA. In the whole population, naïve patients had a higher chance of drug survival (log-rank = 4.06; p = 0.04); in PsA, obese patients had a significantly higher chance to discontinue secukinumab (log-rank = 5.25; p = 0.021). The multivariable Cox regression showed that arthritis was independently associated with a higher risk of secukinumab discontinuation (hazard ratio 2.43; 95% confidence interval 1.06-5.55, p = 0.035) after adjusting for age, sex, gender, BMI, therapy line and PsO severity at baseline. CONCLUSIONS: Our data confirmed a very good response to secukinumab in both PsO and PsA patients. However, presence of arthritis might affect drug survival.
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Artrite Psoriásica , Psoríase , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Índice de Massa Corporal , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/epidemiologiaRESUMO
Osteoarthritis (OA) most commonly affects knee joints, and the next most commonly affected sites are the hands and hips. Three distinct hand OA phenotypes have been described: erosive hand OA (EHOA), nodal hand OA - also known as non-erosive hand OA (non-EHOA) - and first carpometacarpal joint OA. EHOA predominantly affects women and is the most aggressive form of hand OA, characterized by a severe clinical onset and progression, leading to joint damage, disability and reduction of quality of life. Clinical signs of inflammation associated with EHOA include the acute onset of pain, swelling and redness. Moreover, EHOA is characterized by radiographic features such as central erosion, saw-tooth and gull-wing lesions and, rarely, ankylosis. The aim of this Review is to report the latest findings on epidemiology, clinical features, pathology and aetiopathogenesis, biomarkers, imaging modalities and treatments for EHOA. The ongoing development of new hand OA classification criteria should facilitate standardization between studies.
Assuntos
Articulação da Mão , Osteoartrite , Biomarcadores , Feminino , Mãos/patologia , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/patologia , Humanos , Osteoartrite/diagnóstico por imagem , Osteoartrite/epidemiologia , Osteoartrite/genética , Qualidade de VidaRESUMO
OBJECTIVES: To assess the influence of psoriasis on spinal/pelvic radiographic progression and MRI features in early-stage axial spondyloarthritis (axSpA). METHODS: Analysis of baseline data from the Italian SPACE cohort, including patients with chronic back pain (CBP; duration ≥3 months and ≤2 years; onset <45 years) was performed. Patients underwent a diagnostic work-up, including MRI and X-rays of the sacroiliac joints (SIJ), to establish diagnosis of axSpA (Assessment of Spondyloarthritis International Society criteria). Clinical features, disease activity and functional indices, imaging were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRIs were scored by two readers following Spondyloarthritis Research Consortium of Canada score, Stoke Ankylosing Spondylitis Spinal Score System modified by Creemers and modified New York criteria. Characteristics of axSpA patients with/without psoriasis were compared over time with descriptive statistics; multivariate logistic regression model was constructed to assess predictors of spinal/pelvic radiographic progression. RESULTS: Eighty-eight patients had axSpA (84.1% non-radiographic; 15.9% radiographic); 36.4% had psoriasis. Patients with psoriasis were older; less frequently had HLA-B27+ and radiographic sacroiliitis with unilateral/asymmetric pattern and more signs of spondylitis. Functional and disease activity indices decreased with slightly higher BASDAI and BASFI in axSpA with psoriasis. All patients showed slight spinal/pelvic radiographic progression. Patients without psoriasis showed increased sacroiliitis progression and low-grade spinal progression. More inflammatory corner lesions on cervical/thoracic MRI-spine were observed in patients with psoriasis. A significant downtrend of SPARCC SIJ/spine scores in all patients was found. Psoriasis was a predictor of increased spinal progression (odds ratio = 0.18; 95% CI: 0.04, 0.78). CONCLUSIONS: Psoriasis was associated with distinct axSpA features, increased spinal radiographic progression and low-grade radiographic sacroiliitis.