Sex differential impact of comorbidities in spondyloarthritis: data from COMOSPA study.

OBJECTIVES: To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients. METHODS: This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders. RESULTS: We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients. CONCLUSIONS: Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment.

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain.

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation.

Management of Specific Clinical Profiles in Axial Spondyloarthritis: An Expert's Document Based on a Systematic Literature Review and Extended Delphi Process.

INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.

Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER).

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

Prevalence of hypercalcemia in primary hypoadrenocorticism in dogs: Multicenter, retrospective study.

BACKGROUND: Hypoadrenocorticism is an important differential for hypercalcemia. The etiology of hypercalcemia in hypoadrenocorticism in dogs is unclear. OBJECTIVE: To review the prevalence of hypercalcemia and use statistical models to identify clinical, demographic, and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism. ANIMALS: One hundred ten dogs with primary hypoadrenocorticism; 107 with recorded total calcium (TCa), 43 recorded ionized calcium (iCa). METHODS: Multicenter retrospective observational study at 4 UK referral hospitals. Univariable logistic regression analyses were performed to assess the association between independent variables of signalment, hypoadrenocorticism type (glucocorticoid only deficient hypoadrenocorticism [GHoC] vs glucocorticoid and mineralocorticoid deficient hypoadrenocorticism [GMHoC]), clinicopathological variables and hypercalcemia. Hypercalcemia was defined as elevated TCa, an elevated iCa, or both elevated TCa and iCa (Model 1) or as elevated iCa (Model 2). RESULTS: Overall prevalence of hypercalcemia was 34.5% (38/110). The odds of hypercalcemia (Model 1) were increased (P < .05) in dogs with GMHoC ([vs GHoC], OR [odds ratio] = 3.86, 95% confidence interval [CI] 1.105-13.463), higher serum creatinine (OR = 1.512, 95% CI 1.041-2.197), and higher serum albumin (OR = 4.187, 95% CI 1.744-10.048). The odds of ionized hypercalcemia (Model 2) were increased (P < .05) with reduced serum potassium concentration (OR = 0.401, 95% CI 0.184-0.876) and younger age (OR = 0.737, 95% CI 0.558-0.974). CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified several key clinical and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism. These findings aid understanding of the pathophysiology and etiology of hypercalcemia in dogs with primary hypoadrenocorticism.

Sialyltransferase Inhibitor Ac53FaxNeu5Ac Reverts the Malignant Phenotype of Pancreatic Cancer Cells, and Reduces Tumor Volume and Favors T-Cell Infiltrates in Mice.

Hypersialylation is a feature of pancreatic ductal adenocarcinoma (PDA) and it has been related to tumor malignancy and immune suppression. In this work, we have evaluated the potential of the sialyltransferase inhibitor, Ac53FaxNeu5Ac, to decrease tumor sialoglycans in PDA and to revert its malignant phenotype. Sialoglycans on PDA cells were evaluated by flow cytometry, and the functional impact of Ac53FaxNeu5Ac was assessed using E-selectin adhesion, migration, and invasion assays. PDA tumors were generated in syngeneic mice from KC cells and treated with Ac53FaxNeu5Ac to evaluate tumor growth, mice survival, and its impact on blocking sialic acid (SA) and on the tumor immune component. Ac53FaxNeu5Ac treatment on human PDA cells decreased α2,3-SA and sialyl-Lewisx, which resulted in a reduction in their E-selectin adhesion, and in their migratory and invasive capabilities. Subcutaneous murine tumors treated with Ac53FaxNeu5Ac reduced their volume, their SA expression, and modified their immune component, with an increase in CD8+ T-lymphocytes and NK cells. In conclusion, Ac53FaxNeu5Ac treatment weakened PDA cells' malignant phenotype, thereby reducing tumor growth while favoring anti-tumor immune surveillance. Altogether, these results show the positive impact of reducing SA expression by inhibiting cell sialyltransferases and open the way to use sialyltransferase inhibitors to target this dismal disease.

Uveitis in peripheral spondyloarthritis patients: an ancillary analysis of the ASAS-PerSpA study.

Background: Acute anterior uveitis (AAU) is the most frequent extra-musculoskeletal manifestation in spondyloarhtritis (SpA). Previous data on AAU focused on axial disease; therefore, it is not well known whether the clinical characteristics of patients with AAU and recurrent AAU differ between patients with axial and peripheral SpA. Objective: Primary objective was to compare the clinical characteristics of patients with AAU from patients without AAU in axial and peripheral spondyloarthritis (SpA) patients. Secondary objectives were to describe the clinical features of patients with AAU in the subset of patients with peripheral SpA (pSpA) and the clinical characteristics of patients with recurrent AAU in SpA patients. Design: This is an ancillary analysis of the ASAS-PerSpA study which included 3152 patients, 2719 patients with axSpA and 433 with pSpA according to rheumatologist judgement. Methods: Recurrent AAU was defined as the presence of two or more episodes of AAU ever. Univariable and multivariable binary logistic regression analyses were conducted to identify factors associated with the presence of AAU ever and the presence of recurrent AAU. Results: Overall, 663 patients (21%) presented AAU. Of them, 444 (66.9%) presented recurrent episodes. In patients with SpA, HLA-B27 positivity is the most important factor linked to the presence of AAU, odds ratio (OR) = 2.70 (95% CI = 2.04-3.6). In patients with pSpA, HLA-B27 positivity was also the most relevant factor linked to the presence of AAU, OR = 6.08 (95% CI = 2.72-15.68). Moreover, disease duration, younger age and higher body mass index (BMI) were the only factors slightly linked to the presence of recurrent episodes, OR = 1.03 (95% CI = 1.01-1.04), OR = 1.01 (95% CI = 1.00-1.03) and OR = 1.04 (95% CI = 1.01-1.08), respectively. Conclusion: HLA-B27 positivity is the most relevant factor linked to AAU risk in SpA patients, and this association is even stronger in those patients with pSpA. Moreover, our study did not find an association between HLA-B27 positivity and recurrent AAU in SpA patients.

Electromyographic activity of posterior kinetic chain muscles during hamstring strengthening exercises.

OBJECTIVES: To compare the muscle activation of the biceps femoris (BF), semitendinosus (ST), gluteus maximus (GM), and contralateral erector spinae (ES) in four specific eccentric hamstring-oriented exercises using overground maximal sprints as an EMG normalization method. DESIGN: cross-sectional study. PARTICIPANTS: twenty-four healthy athletes participated in this study. MAIN OUTCOME MEASURES: The maximum EMG activation of all targeted muscles was measured during maximal sprints and four hamstring exercises: Nordic hamstring (NH), Russian belt (RB), glider (GL) and lying kick (LK). Maximum EMG activation during sprints were used to normalize EMG muscle activation. RESULTS: RB and GL showed lower hamstrings activation (from 15.71% to 39.23% and from 26.34% to 31.23%, respectively), so these exercises may be used as the first step of the retraining. The higher hamstring activation was reached in the NH (from 20.15% to 66.81%) and the LK (from 50.5% to 61.2%). Regarding muscles comparison, BF and ST were the most dependent on the exercise ranging from 26.67% to 62.22%, and from 26.34% to 66.81%, respectively. CONCLUSIONS: Muscle activation is dependent on the exercise procedure. RB and GL should be used as a first step because of their low activation. Instead, NH and LK should be used at the last phases of retraining process. Considering the synergistic activation of the PKC muscles during LK, and because of its unilateral and explosive characteristics, LK seems a suitable exercise for retraining PKC muscles in general.

Exploring the Role of Galectins in Cancer : In Vitro and In Vivo Approaches.

Galectins have been linked to tumorigenesis since 1975, even before this family of proteins was given its name. Since then, hundreds of papers have analyzed the role of different galectins in cancer development and progression, deciphering their involvement in many different pathological events, from the regulation of cell cycle, to angiogenesis, metastasis, and immune attack evasion. Importantly, the tumor galectin profile is often altered in many cancers and aberrant levels of some of the members of this family have been considered in diagnosis and frequently correlated with patient prognosis and clinicopathological characteristics. In this chapter, we summarize most frequent techniques employed in cancer research to interrogate the role of galectins, using Gal-1 to illustrate one member of the family and pancreatic cancer as an experimental model. We will cover from techniques employed to detect their expression (tissue and blood samples) to the most frequent tools used to change expression levels and the cell line-based in vitro studies and murine preclinical models used to explore their role in tumor progression and/or clinical translation.

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO.

BACKGROUND: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi). METHODS: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients' groups at each time point were assessed using a linear mixed-effect model. RESULTS: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP). CONCLUSIONS: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Antimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure.

BACKGROUND/OBJECTIVES: Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. METHODS: Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. RESULTS: The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84-7.25], p < 0.0002), valvulopathy (6.33 [3.41-11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p = 0.0015). Female sex (0.46 [0.25-0.88], p = 0.0147) and antimalarials (0.28 [0.17-0.45], p < 0.000) proved to be protective factors. CONCLUSIONS: Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.

Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission.

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis.

BACKGROUND: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. METHODS: AXL was analysed by immunohistochemistry in human pancreatic tissue samples. RNA expression analysis was performed using TCGA/GTEx databases. The plasma concentrations of sAXL, its ligand GAS6, and CA19-9 were studied in two independent cohorts, the HMar cohort (n = 59) and the HClinic cohort (n = 142), including healthy controls, chronic pancreatitis (CP) or PDAC patients, and in a familial PDAC cohort (n = 68). AXL expression and sAXL release were studied in PDAC cell lines and murine models. FINDINGS: AXL is increased in PDAC and precursor lesions as compared to CP or controls. sAXL determined in plasma from two independent cohorts was significantly increased in the PDAC group as compared to healthy controls or CP patients. Patients with high levels of AXL have a lower overall survival. ROC analysis of the plasma levels of sAXL, GAS6, or CA19-9 in our cohorts revealed that sAXL outperformed CA19-9 for discriminating between CP and PDAC. Using both sAXL and CA19-9 increased the diagnostic value. These results were validated in murine models, showing increased sAXL specifically in animals developing PDAC but not those with precursor lesions or acinar tumours. INTERPRETATION: sAXL appears as a biomarker for early detection of PDAC and PDAC-CP discrimination that could accelerate treatment and improve its dismal prognosis. FUNDING: This work was supported by grants PI20/00625 (PN), RTI2018-095672-B-I00 (AM and PGF), PI20/01696 (MG) and PI18/01034 (AC) from MICINN-FEDER and grant 2017/SGR/225 (PN) from Generalitat de Catalunya.

Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study.

OBJECTIVE: To analyse the influence of HLA-B27 in the phenotypical expression of peripheral spondyloarthritis (pSpA). METHOD: This is an observational cross-sectional study using data from the Assessment of SpondyloArthritis international Society perSpA registry, including all patients with an available HLA-B27 test result and with a diagnosis of pSpA or psoriatic arthritis (PsA) as per rheumatologist's judgement. Demographic and clinical data, presence of extra musculoskeletal manifestations (EMM) and fibromyalgia were the variables included in a simple and multiple logistic regression model to assess their association to HLA-B27 positivity. RESULTS: From the 4465 patients included in the registry, 790 were classified as having either pSpA or PsA and had the HLA-B27 typing available. HLA-B27-positive patients presented a male predominance, had an earlier disease onset and a shorter diagnostic delay compared with the negatives. HLA-B27-positive patients presented a higher frequency of axial involvement, radiographic sacroiliitis, enthesitis and uveitis. Also, root joint involvement, poliarticular joint patern and tarsitis were significantly higher within HLA-B27-positive patients. Furthermore, we did not observe any association between the presence of HLA-B27 and peripheral joint damage, dactylitis, other EMM (psoriasis, inflammatory bowel disease) or fibromyalgia.The multivariable analysis confirmed the independent association of HLA-B27 positivity with male sex, an earlier onset of the disease, the presence of axial involvement, tarsitis and uveitis. SUMMARY: In summary, the presence of HLA-B27 in pSpA patients was associated with earlier disease onset and higher axial involvement, tarsitis and uveitis, but not with other EMM, fibromyalgia or peripheral structural damage.

Sex-associated and gender-associated differences in the diagnosis and management of axial spondyloarthritis: addressing the unmet needs of female patients.

Emerging evidence suggests that axial spondyloarthritis (axSpA) should not be seen as a predominantly male disease, as the non-radiographic form occurs with roughly equal frequency in women and men. However, men and women experience this disease differently. The purpose of this review is to highlight sex-associated and gender-associated differences in the patient's journey through the diagnosis and management of axSpA, in order to increase the awareness about the unmet needs of female axSpA patients.Female patients experience a longer diagnostic delay compared with men, possibly due to the different pattern of clinical presentations across genders. Therefore, it is crucial to sensitise physicians to pay attention and identify the red flags of axSpA in women and promote early referral to a rheumatologist. Women with a diagnosis of axSpA experience greater limitations in physical function, although they have less structural spinal damage compared with men. Women tend to have less adherence and a lower response to treatment, so more gender-oriented data are needed about drugs used for axSpA, especially biological disease-modifying antirheumatic drugs.Lifestyle factors have a strong impact on the disease course. Interventions regarding physical activity, smoking cessation and diet should be communicated to the patients, with particular attention to the gender-related cultural background.Patients of childbearing age living with axSpA should be engaged in a discussion about reproductive health, in terms of preservation of fertility, management of pregnancy and delivery and use of biologic drugs during pregnancy and breastfeeding.

Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference? An observational study / Comparación de la actividad de la enfermedad en pacientes de espondilitis anquilosante con terapia de anti-TNF o AINE. ¿Existe alguna diferencia? Estudio observacional

Objective: To assess whether there are any real-life differences between ankylosing spondylitis (AS) patients treated with NSAID or TNF inhibitors (TNFi) regarding disease activity.Methods: This is an observational transversal unicentric study with retrospective retrieval of data from clinical records of all AS patients attended in our hospital. We compared clinical activity measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores between patients treated with NSAID and those treated with TNFi, in terms of low disease activity defined as BASDAI<4, and inactivity when BASDAI≤2. As secondary variables, we also collected epidemiological, clinical and radiological data from all those patients. Results: A total of 152 AS patients (81% male), with an average age of 49.45±12.38 years and a disease duration of 13.5±9.79 years were included in the study. Eighty-nine patients (58.6%) were treated with NSAID and 63 (41.4%) with TNFi. The proportion of patients with low disease activity and inactive disease was significantly higher in the TNFi treatment group compared to the NSAID group (81 vs. 47, P=.0001) and (44 vs. 24, P=.007), respectively. Patients treated with NSAIDs also showed significantly more global pain and night pain than those under TNFi therapy. The BASFI score and especially the type of treatment (NSAID or TNFI) were the only variables independently associated with low disease activity or inactive disease. Conclusion: In real world practice, AS patients under TNFi treatment show a better control of clinical symptoms than those under NSAIDs.(AU)

Objetivo: Evaluar si existen diferencias entre los pacientes con espondilitis anquilosante (EA) tratados con AINE o inhibidores del TNF (anti-TNF), con relación a la actividad de la enfermedad en la vida real. Métodos: Estudio observacional transversal unicéntrico con recopilación retrospectiva de datos de historias clínicas de todos los pacientes de EA examinados en nuestro hospital. Comparamos la actividad clínica, medida con la puntuación del Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), entre los pacientes tratados con AINE y los tratados con anti-TNF, en términos de baja actividad de la enfermedad definida como BASDAI<4 e inactividad, con BASDAI≤2. Como variables secundarias recopilamos también los datos clínicos, epidemiológicos y radiológicos de dichos pacientes. Resultados: Incluimos en el estudio un total de 152 pacientes de EA (81% varones), con una edad media de 49,45±12,38años y una duración de la enfermedad de 13,5±9,79años. Ochenta y nueve pacientes (58,6%) fueron tratados con AINE y 63 (41,4%) con anti-TNF. La proporción de pacientes con baja actividad de la enfermedad e inactividad fue significativamente superior en el grupo de terapia anti-TNF, en comparación con el grupo AINE: 81 vs. 47, p=0,0001, y 44 vs. 24, p=0,007, respectivamente. Los pacientes tratados con AINE reflejaron también un dolor global significativamente mayor que aquellos con terapia de anti-TNF. La puntuación BASFI, y especialmente el tipo de tratamiento (AINE o anti-TNF), fueron las únicas variables independientemente asociadas a baja actividad de la enfermedad o a inactividad de esta. Conclusión: En la práctica real, los pacientes de EA con terapia anti-TNF reflejan un mejor control de los síntomas clínicos que aquellos con tratamiento de AINE.(AU)

Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference? An observational study.

OBJECTIVE: To assess whether there are any real-life differences between ankylosing spondylitis (AS) patients treated with NSAID or TNF inhibitors (TNFi) regarding disease activity. METHODS: This is an observational transversal unicentric study with retrospective retrieval of data from clinical records of all AS patients attended in our hospital. We compared clinical activity measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores between patients treated with NSAID and those treated with TNFi, in terms of low disease activity defined as BASDAI<4, and inactivity when BASDAI≤2. As secondary variables, we also collected epidemiological, clinical and radiological data from all those patients. RESULTS: A total of 152 AS patients (81% male), with an average age of 49.45±12.38 years and a disease duration of 13.5±9.79 years were included in the study. Eighty-nine patients (58.6%) were treated with NSAID and 63 (41.4%) with TNFi. The proportion of patients with low disease activity and inactive disease was significantly higher in the TNFi treatment group compared to the NSAID group (81 vs. 47, P=.0001) and (44 vs. 24, P=.007), respectively. Patients treated with NSAIDs also showed significantly more global pain and night pain than those under TNFi therapy. The BASFI score and especially the type of treatment (NSAID or TNFI) were the only variables independently associated with low disease activity or inactive disease. CONCLUSION: In real world practice, AS patients under TNFi treatment show a better control of clinical symptoms than those under NSAIDs.

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

OBJECTIVE: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. RESULTS: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2-4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. CONCLUSIONS: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy.

Correction to: Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database.

An amendment to this paper has been published and can be accessed via the original article.

Hormonal Dependence and Cancer in Systemic Lupus Erythematosus.

OBJECTIVE: To estimate the incidence and analyze any cancer-associated factors in patients with systemic lupus erythematosus (SLE), differentiating between hormone-sensitive (HS) and non-HS cancers. METHODS: This was a retrospective multicenter study of a patient cohort from the Systemic Lupus Erythematosus Registry of the Spanish Society of Rheumatology. Included were the first cancer post-SLE diagnosis, clinical and sociodemographic information, cumulative damage, severity, comorbidities, treatments, and refractoriness. Cancers were classified as HS (prostate, breast, endometrium, and ovarian) and non-HS (the remainder). The standardized incidence ratio (SIR) was calculated and logistic regression models were built. RESULTS: A total of 3,539 patients (90.4% women) were included, 154 of whom had cancer (91% female), and 44 had HS cancer (100% female). The cancer SIR was 1.37 (95% confidence interval [95% CI] 1.15-1.59), with higher values in women age <65 years (SIR 2.38 [95% CI 1.84-2.91]). The SIR in women with HS versus non-HS cancer was 1.02 (95% CI 0.13-1.91) and 1.93 (95% CI 0.98-2.89). In HS versus non-HS cancers, SLE diagnostic age (odds ratio [OR] 1.04 [P = 0.002] versus 1.04 [P = 0.019]), and period of disease evolution (OR 1.01 [P < 0.001] versus 1.00 [P = 0.029]) were associated with cancer. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (OR 1.27 [P = 0.022]) and angiotensin-converting enzyme (ACE) inhibitor prescriptions (OR 2.87 [P = 0.048]) were associated with non-HS cancers. CONCLUSION: Cancer incidence in patients with SLE was higher than in the Spanish population, particularly among young women. This increase might be due to non-HS cancers, which would be associated with SLE involving greater cumulative damage where more ACE inhibitors are prescribed.