Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry.

INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.

Long-term retention of golimumab treatment in clinical practice in a large cohort of patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis.

AIM: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors. METHODS: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). RESULTS: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation. CONCLUSION: Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.

Female Sex, Age, and Unfavorable Response to Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis: Results of Statistical and Artificial Intelligence-Based Data Analyses of a National Multicenter Prospective Registry.

OBJECTIVE: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy. METHODS: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)-based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C-reactive protein level (ASDAS-CRP). RESULTS: Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow-up (P = 0.018) and a lesser reduction of the ASDAS-CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi. CONCLUSION: In this national multicenter registry, female sex was associated with less response to a first-line TNFi by the second year of follow-up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Biologic therapy in refractory neurobehçet's disease: a multicentre study of 41 patients and literature review.

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.

Myo-Spain: Spanish Registry of patients with idiopathic inflammatory myopathy. Methodology.

OBJECTIVES: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. METHODS: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. CONCLUSIONS: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients.

OBJECTIVES: To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). METHODS: Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. RESULTS: We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), CONCLUSIONS: CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.

Myo-Spain: Spanish Registry of Patients with Idiopathic Inflammatory Myopathy. Methodology. / Myo-Spain: Registro de pacientes con miopatía inflamatoria idiopática de España. Metodología.

OBJECTIVES: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. METHODS: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. CONCLUSIONS: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project.

BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.

[The Challenge of Care Continuity in Complex Chronic Patients from Nurses' Perspective]. / La enfermera ante el reto de la gestión del paciente crónico complejo.

Introduction: The complex chronic disease requires a model of care based found on multidisciplinary teams. The aim of this study was to analyse the development of nursing leadership in managing the complex chronic patient (CCP) and to identify how the resources for the attention and follow up of these patients are managed. Method: A qualitative descriptive approach was followed through participant observation, in-depth interview to 7 health professionals (5 nurses, a doctor, and a social worker) and a discussion group with 9 Primary Health Care nurses from a intentional sample. Discourse analysis was undertaken following Conde approach: fixing discurse positions, creating and analyzing symbolic configuratons, analyzing and interpreting semantic configurations and drawing up the discourse. Results: From discourse analysis two main dimensions emerged on the nursing leadership and management: a) nursing as the leader of care: the need of nursing leadership and of improvement in the coordination structures were recognized, and b) nursing as resources manager in the CCP care related to social and health risks and resources coordination. Conclusions: Our findings enhance the case management and the home delivery care as foundations to be effective handle of CCP, where nursing has a privileged role.

ECAMulticapa: Effectiveness of double-layered compression therapy for healing venous ulcers in primary care: a Study Protocol.

BACKGROUND: Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated. METHOD/DESIGN: Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat. DISCUSSION: The study results can contribute to improving the care and quality of life of patients with venous ulcers, decreasing healing times and healthcare expenditure and contributing to the consistent treatment of these lesions. TRIAL REGISTRATION: This study has been recorded in the Clinical Trials.gov site with the code NCT02364921. 17 February 2015.

Thrombotic manifestations in SAPHO syndrome. Review of the literature.

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted.