Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Adherence to subcutaneous biological therapies in patients with inflammatory rheumatic diseases and inflammatory bowel disease: a systematic review.

Aim: To assess adherence to subcutaneous biologicals in adults with inflammatory rheumatic diseases or inflammatory bowel disease and evaluate factors possibly associated with adherence. Materials & methods: Systematic searches were conducted of main databases from January 2000 to June 2019. Results: 41 articles (32 full papers and nine abstracts) were included in the review. Among studies which used a medication possession ratio threshold of ≥80% as the end point, adherence varied from 28.8 to 89.4%. Possible predictors of adherence were older age, professional or family member support, belief in medication necessity, lower concerns about medication and monthly versus weekly administration. Conclusion: Considerable variability in adherence rates across published studies reflects study heterogeneity and the absence of a 'gold standard' to measure adherence.

Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología / A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics

Objetivo: El paradigma actual en el tratamiento de la artritis reumatoide (AR) contempla el diagnóstico temprano y el uso precoz de fármacos modificadores de enfermedad (FAME) para alcanzar la remisión o baja actividad inflamatoria, lo cual, se conoce como «treat to target» (T2T). El objetivo del trabajo es desarrollar un indicador compuesto (IC) para evaluar la calidad asistencial en el manejo de los pacientes con AR atendiendo a la estrategia T2T y a otras recomendaciones generales para la atención de estos pacientes. Material y método: La construcción del IC siguió las fases: 1) selección de los criterios de calidad mediante un juicio de expertos; 2) priorización de los criterios, a partir de un Delphi con 20 expertos; 3) diseño de los indicadores de calidad, y 4) cálculo del IC ponderado. La fuente de información para el cálculo del IC son las historias clínicas de los pacientes con AR. Resultados: De los 37 criterios seleccionados, 12 necesitaron una segunda ronda Delphi. Se priorizaron 31 criterios, los cuales presentaron una mediana en relevancia y factibilidad, en las rondas Delphi, mayor o igual a 7,5, con un rango intercuartílico inferior a 3,5, y un grado de acuerdo (puntuación mayor o igual a 8) igual o superior al 80%. Conclusiones: El IC construido, consensuado y ponderado, permite evaluar la calidad asistencial de los pacientes con AR, en las Unidades de Reumatología de hospitales españoles, ofreciendo una medida resumen válida y fácilmente interpretable

Objective: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. Material and method: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. Results: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. Conclusions: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study / Prevalencia de comorbilidades en artritis reumatoide y evaluación de su manejo en la clínica diaria: cohorte española del estudio COMORA

Objectives: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). Methods: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. Results: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. Conclusions: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal

Objetivos: Describir la prevalencia de comorbilidades en pacientes con AR en España y discutir sobre su manejo en la clínica diaria utilizando los datos de la cohorte española del estudio internacional COMORA. Métodos: Subanálisis nacional del estudio COMORA en el que se analizaron las características demográficas y clínicas de 200 pacientes con AR (1987 ACR) y las prácticas rutinarias para el cribado y la prevención de eventos cardiovasculares (CV), gastrointestinales y pulmonares, infecciones, cáncer, osteoporosis y depresión. Resultados: Los pacientes tenían una edad media de 58 años, una duración media de la enfermedad de 10 años, un DAS28 de 3,3 y el 25% estaba en remisión (DAS28 <2,6). El 22% de los pacientes presentaba al menos una comorbilidad, principalmente depresión (27%) y obesidad (26%). El 5% tenía historia de infarto de miocardio, el 1% de ictus y el 6% de tumor sólido. Una puntuación de Framingham >20% (51%), tener hipercolesterolemia (46%), hipertensión (41%) y fumar (25%) fueron los factores de riesgo CV más comunes. En relación con el cáncer de próstata, colon y piel, solo el 9, 10 y el 18% de los pacientes, respectivamente, estaban óptimamente controlados. Las infecciones tampoco se manejaban de forma óptima, con solo el 7 y el 17% de los pacientes vacunados contra la influenza y neumococo, respectivamente, al igual que la osteoporosis, con el 47% suplementados con la vitamina D y el 56% con una densitometría realizada. Conclusiones: En España, la prevalencia de comorbilidades y factores de riesgo CV en pacientes con AR establecida y avanzada es relativamente alta, y su manejo en la clínica diaria continúa siendo subóptimo

Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature / Nefritis lúpica membranosa pura: descripción de una cohorte de 150 pacientes y revisión de la literatura

Objectives: The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN. Methods: We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA. Results: Mean age was 34.2±12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98±0.78mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death. Conclusions: Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis

Objetivos: Los conocimientos sobre el curso y el desenlace a largo plazo de la nefritis lúpica membranosa (NLM) pura son todavía escasos. El objetivo de este estudio es evaluar las características clínicas, curso, desenlace e indicadores pronósticos de la NLM y determinar el impacto de la etnicidad y tipo de cobertura sanitaria en el curso y pronóstico de la NLM. Métodos: Se realizó una revisión retrospectiva de las historias de 150 pacientes con NLM de España y Estados Unidos. Resultados: La edad media fue 34,2±12,5 y el 80% eran mujeres. El 68% de los pacientes tenían síndrome nefrótico al diagnóstico. La creatinina sérica media fue 0,98±0,78mg/dl. El 6% de los pacientes fallecieron y el 5,3% desarrollaron insuficiencia renal terminal (IRT). El sexo masculino, la hipertensión, la dislipemia, la alta proteinuria basal, la alta creatininemia y un aclaramiento de creatinina reducido predijeron el desarrollo de IRT. La edad, la insuficiencia cardíaca, la arteriopatía periférica, la hemodiálisis y el no haber recibido micofenolato de mofetilo o antimaláricos predijeron el fallecimiento. Conclusiones: La NLM pura suele debutar con síndrome nefrótico, alta proteinuria y creatininemia normal. Su pronóstico es favourable en términos de mantenimiento de la función renal aunque la proteinuria habitualmente persiste durante el seguimiento. La enfermedad cardiovascular basal y no tener cobertura sanitaria se relacionan con mal pronóstico

Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature.

OBJECTIVES: The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN. METHODS: We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA. RESULTS: Mean age was 34.2±12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98±0.78mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death. CONCLUSIONS: Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis.

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.

OBJECTIVES: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.

A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics. / Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología.

OBJECTIVE: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. MATERIAL AND METHOD: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. RESULTS: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. CONCLUSIONS: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure.

Correction to: The beliefs of rheumatoid arthritis patients in their subcutaneous biological drug: strengths and areas of concern.

In the original publication, the family name of the last author was incorrect. The correct name should read as Jaime Calvo-Alén.

The beliefs of rheumatoid arthritis patients in their subcutaneous biological drug: strengths and areas of concern.

Patients' beliefs about their prescribed medication are an important factor influencing intentional non-adherence. This study describes rheumatoid arthritis (RA) patients' beliefs about their subcutaneous (SC) biological medication through the Beliefs about Medicines Questionnaire (BMQ), and potential associations. As part of the ARCO study (Study on Adherence of Rheumatoid arthritis patients to subCutaneous and Oral drugs), patients completed the BMQ specifically for their SC biological medication, encompassing a necessity and a concerns scale. The medication possession ratio (MPR) was calculated to assess adherence to the SC biological medication. The BMQ was completed by 321 patients. Between 71.0 and 89.7% of patients agreed/strongly agreed with necessity scale statements, and only 7.2% had low necessity scores. Between 20.0 and 49.8% of patients agreed/strongly agreed with four of five concern scale statements, and 72.3% agreed/strongly agreed with the concern statement regarding long-term medication effects. The percentage with high concerns was 58.9%, and was higher in patients not satisfied with, or with less fulfillment of, tolerability expectations. Non-adherence percentages were, respectively, 13.8 and 13.0% (p = 0.919) in those with high or low necessity, and 16.0 and 10.6% (p = 0.171) in those with high or low concerns. Most patients were categorized as 'ambivalent' (58.5%; high necessity/high concerns) or 'accepting' (36.1%; high necessity/low concerns) of their SC biological medication. The BMQ identified patients' concerns with their SC biological medication. Because patients' concerns could influence non-adherence to medication and future outcomes, physicians should address this issue in the clinic by informing patients and setting clear expectations.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. METHODS: Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. RESULTS: We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. CONCLUSIONS: jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

Identification of patients at risk of non-adherence to oral antirheumatic drugs in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an ARCO sub-study.

The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18 years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky-Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6 years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48 years; 37.5%) was double that recorded in patients aged >48 years (p = 0.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (p = 0.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Non-adherence to subcutaneous biological medication in patients with rheumatoid arthritis: a multicentre, non-interventional study.

OBJECTIVES: To evaluate non-adherence to prescribed subcutaneous biologicals in rheumatoid arthritis (RA) patients in Spain. METHODS: ARCO (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs) was a multicentre, non-interventional retrospective study involving 42 rheumatology clinics from representative hospitals throughout Spain. The primary objective was to assess the percentage of patients (aged ≥18 years with an established RA diagnosis) with non-adherence to prescribed subcutaneous biologicals using clinical records and hospital pharmacy dispensing logs as the primary information sources. Adherence was assessed using the Medication Possession Ratio (MPR). Additionally, patients completed the Morisky-Green Medication Adherence Questionnaire. RESULTS: A total of 364 patients (77.5% females, mean age 54.9 years, median RA duration since diagnosis 7.8 years) were enrolled in ARCO. Non-adherence (MPR ≤80%) was reported in 52/363 evaluable patients (14.3%), and was lower in patients receiving initial monthly drug administration (6.4%) than with weekly (17.4%; p=0.034) or every two weeks (14.4%; p=0.102) administration. By multivariate analysis, non-adherence was positively associated with RA duration above the median and with using induction doses. Monthly administration, compared to weekly administration, was inversely associated with non-adherence. Age, gender, order of administration, and changes in the interval of administration, showed no association with non-adherence. Compared with the MPR, the Morisky-Green questionnaire performed poorly in detecting non-adherence. CONCLUSIONS: Non-adherence to the prescribed subcutaneous biological drug occurred in 14.3% of patients with RA. Patients using the most convenient administration period (i.e. monthly) had better adherence than those using more frequent dosing schedules.

Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER).

The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ±â€Š12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81-3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014). More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.

The COL1A1 SP1 polymorphism is associated with lower bone mineral density in patients treated with valproic acid.

OBJECTIVE: The aim of this study was to determine the possible relationship between the Sp1 polymorphism of gene COL1A1 and bone metabolism disorder in individuals with epilepsy. METHODS: To this end, we carried out an observational cross-sectional study on 64 patients in monotherapy with an antiepileptic drug. The patients were classified on the basis of the presence of the 's' allele of the COL1A1 Sp1 polymorphism. RESULTS: In the patients with SS, the standardized bone mineral density (sBMD) in the left femoral neck was 1024.9±206.1 mg/cm, whereas in the patients with Ss or ss, the density was significantly lower, 917±141.4 mg/cm (P=0.027), as was the femoral t-score (0.72±1.67 vs. -0.29±1.15, P=0.01). The values in the lumbar spine were equally greater in those with SS: 1219.1±236.3 versus 1090.5±142.7 mg/cm for the sBMD (P=0.018) and 0.67±1.98 versus -0.34±1.16 for the lumbar t-score (P=0.023). The bone biomarkers showed no significant differences nor did the 25-OH vitamin D and parathormone values. In the patient group treated with valproic acid (VPA), the densitometric values were significantly lower in the Ss or ss patients compared with SS homozygotes: 887.1±142.6 versus 1120.6±198.2 mg/cm for femoral sBMD (P=0.02), 990±98.1 versus 1417±251.2 mg/cm for lumbar sBMD (P=0.001). Of the patients who were carriers of the 's' allele and who were treated with VPA, 86% achieved osteopenia values. CONCLUSION: In our study, the presence of the 's' allele of the COL1A1 Sp1 polymorphism in individuals with epilepsy was related to lower bone BMD (lumbar and femoral). This relationship seemed to be further apparent in the patients undergoing treatment with VPA.

Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus.

OBJECTIVES: The objective of this study is to determine the prevalence of fibromyalgia (FM) in systemic lupus erythematosus (SLE) patients and to study its relationship to depression and other SLE-related factors. METHODS: A cross-sectional data analysis from the RELESSER-Transversal Spanish Registry, which includes SLE patients in a national multicentre retrospective charts review, was performed. INCLUSION CRITERIA: patients who fulfilled ≥4 ACR 1997 SLE criteria. Main variables were disease duration, depression, sociodemographics, comorbidities, SLE activity symptoms, serological findings, therapies and different disease status indices. Statistical analyses included a descriptive, associative and logistic regression analyses. A literature review was performed. RESULTS: 3,591 SLE patients were included, 90.1% women, 34.6 years of age at diagnosis (SD 14.6 years) and 93.1% Caucasians. FM prevalence was 6.2%. SLE patients with disease duration >5 years showed more FM than those with duration <5 years: 6.9% vs. 4.0%, respectively (p<0.05). SLE-FM patients showed higher prevalence of depression compared to non-FM-SLE patients: 53.1% vs. 14.6%, respectively (p<0.001). After adjusting by risk factors, the OR (CI) of suffering depression in FM-SLE patients was 6.779 (4.770-9.636), p<0.001. The OR of having secondary Sjögren's 2.447 (1.662-3.604), p<0.001, photosensitivity 2.184 (1.431-3.334), p<0.001, and oral ulcers 1.436 (1.005-2.051), p=0.047. CONCLUSIONS: Prevalence of FM in Caucasian SLE patients was high compared to the general population, and was significantly higher in those in later stages of disease. SLE patients with depression showed a strong risk of developing FM. Photosensitivity, oral ulcers and secondary Sjögren's were the only SLE-related factors associated with FM.

Patterns of use and dosing of tocilizumab in the treatment of patients with rheumatoid arthritis in routine clinical practice: the ACT-LIFE study.

The aim of the study was to identify and describe the patterns of use of tocilizumab in clinical practice to ensure safety and optimal management of rheumatoid arthritis (RA). This is a 12-month prospective observational study in patients with moderate or severe RA of ≥6 months' duration who have started tocilizumab after failure of at least one previous disease-modifying antirheumatic drug (DMARD) including TNF inhibitors. For some analyses, patients were categorized by the use of tocilizumab as monotherapy or in combination, and by previous use of biological therapy. Overall, 379 were evaluable (84.4 % received tocilizumab after prior biologics and 78.4 % in combination with classic DMARDs). Tocilizumab was discontinued in 68/379 (17.9 %) patients after a median of 6.7 (3.7-10.4) months, mainly due to a lack of efficacy (24/379, 6.3 %) and adverse events (23/379, 6.1 %). Of 131 temporary interruptions of tocilizumab required in 101/379 (26.6 %) patients, 81/131 (61.8 %) were related to adverse events, and in 120/131 (91.6 %) cases, tocilizumab was reintroduced at 8 mg/kg. Thirty-six tocilizumab dose reductions occurred in 34/379 (9 %) patients due to abnormal laboratory values in 20/34 (55.6 %) cases. DAS28-ESR scores decreased from baseline (5.6 ± 1.0) to week 24 (3.0 ± 1.4) and week 52 (2.7 ± 1.3). DAS28 response differed between biologics-naive and biologics-experienced patients, both at weeks 24 and 52. In clinical practice, tocilizumab is effective in RA while retaining the expected safety and tolerability profile. Tocilizumab seems to be more effective for biologics-naive patients than for biologics-experienced patients, while it proves to be similarly effective when used in combination or monotherapy.

Comprehensive description of clinical characteristics of a large systemic lupus erythematosus cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) with emphasis on complete versus incomplete lupus differences.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.

Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment. METHODS: This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents. RESULTS: The mean ± SD age of the patients (8 men and 26 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections. CONCLUSION: TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.