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Purpose: To describe the clinical and epidemiological characteristics of patients with Vogt-Koyanagi-Harada (VKH) disease in Spain. Methods: This was a retrospective multicenter analysis of data from VKH patients followed for at least 6 months. The data collected were related to demographics, clinical manifestations, treatments, and complications. Results: Participants were 112 patients (224 eyes), from 13 tertiary referral centers, of mean age 37.5 ± 14.7 years; 83.9% were women. Ethnicities were 61.6% Caucasian and 30.4% Hispanic. The disease was classified as complete in 16.1%, incomplete in 55.4%, and probable in 28.6%. When seen for the first time, the clinical course was acute in 69.6%, recurrent chronic in 15.2%, and chronic in 14.3%. The most frequent treatment was corticosteroids (acute stage 42.2%, maintenance stage 55.6%). The most common complications were cataract (41.1%) and ocular hypertension (16.1%). In most eyes, visual acuity was improved (96.7%) or remained stable at the end of follow up. Conclusion: VKH in Spain mostly affects women and presents as incomplete acute stage disease. Visual prognosis is good. Cataract and glaucoma are the two most frequent complications.

Resumen Objetivo Generar recomendaciones sobre el bloqueo de la interleucina 6 (IL-6) en pacientes con artritis reumatoide (AR), basadas en la mejor evidencia y experiencia. Metodos Se selecciono a 10 expertos reumatologos en el manejo de los inhibidores de la IL-6. Los 2 coordinadores generaron 23 preguntas sobre el bloqueo de la IL-6 en la AR (perfiles de indicacion, eficacia, seguridad, etc.) para ser contestadas mediante una revision sistematica de la literatura. Con base en las preguntas se definieron los criterios de inclusion y exclusion, y las estrategias de busqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los articulos resultantes de la busqueda. Se generaron tablas de evidencia. Paralelamente, se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores propusieron 8 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunion de grupo nominal con el resto de los expertos. Para cada recomendacion se establecio el nivel de evidencia y grado de recomendacion, y el grado de acuerdo mediante un Delphi. Se definio acuerdo si al menos el 80% de los participantes contestaban si a la recomendacion (si o no). Resultados Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinacion, en pacientes refractarios o intolerantes, la evaluacion de su respuesta, la optimizacion o la gestion del riesgo. Conclusiones Este documento pretende resolver algunos interrogantes clinicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR.

Resumen Objetivo El paradigma actual en el tratamiento de la artritis reumatoide (AR) contempla el diagnostico temprano y el uso precoz de farmacos modificadores de enfermedad (FAME) para alcanzar la remision 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 atencion de estos pacientes. Material y metodo La construccion del IC siguio las fases: 1) seleccion de los criterios de calidad mediante un juicio de expertos ; 2) priorizacion de los criterios, a partir de un Delphi con 20 expertos; 3) diseno de los indicadores de calidad, y 4) calculo del IC ponderado. La fuente de informacion para el calculo del IC son las historias clinicas 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 intercuartilico inferior a 3,5, y un grado de acuerdo (puntuacion 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 Reumatologia de hospitales espanoles, ofreciendo una medida resumen valida y facilmente interpretable.

OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:6 pages:1073-1085 ispartof: location:United States status: published

Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants’ clinical experience when only low quality evidence was available. A total of 18 recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

SUMMARYBackgroundClinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification.MethodsWith the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. In addition, an inception cohort was prospectively followed for 6 and 14 months to validate the results and analyze if cluster assignment changed or not with time.ResultsFour clusters were identified. Three clusters were aberrant, representing ‘inflammatory’, ‘lymphoid’, and ‘interferon’ patterns each including all diagnoses and defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern and accumulated also healthy controls. An independent inception cohort showed that with time, the molecular clusters remain stable, showing that single aberrant molecular signatures characterize each individual patient.ConclusionsPatients with SADs can be jointly stratified into three stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of therapy non-responsiveness marking a paradigm shift in the view of SADs.

Background Remission and Low Disease activity state (LDAS) are the treat to target (T2T) outcomes used Systemic Lupus Erythematosus (SLE). Lupus Impact Tracker (LIT), a ten item unidimensional patient reported (PRO) tool with good psychometric properties and responsiveness including to composite response Index (SRI) and T2T outcomes. SLE patients often fibromyalgia (FM). We report discriminant validity of LIT to T2T outcomes in SLE patients stratified by FM from the largest European SLE registry- cohort. Methods Observational, multi-center data from 1364 adult patients with SLE meeting 1997 ACR criteria were obtained. This included demographics, LIT, disease activity-DA (SLEDAI) and medications. Remission off therapy (ROFT) was defined as SLEDAI=0 without prednisone or Immunosuppressive/s. Remission on-therapy (RONT) was SLEDAI=0 and a prednisone dose 5 mg/day and/or Immunosuppressive/s. LDAS (modified) was SLEDAI 4, prednisone dose 9 mg/day and/or maintenance immunosuppressive/s. Non-optimal (NO) disease status was SLEDAI >4 and/or prednisone dose >9 mg/day and/or immunosuppressive/s in induction dose. LIT values were compared between T2T groups using mixed models among (a) all patients, (b) with and (c) without FM. For Model 1 : RONT and LDAS were combined (given relatively very low DA and lower prevalence of steroid use in LDAS) and compared with NO and ROFT. For model 2, all 4 T2T categories were used. Results 1232/1364 (90%) were women, and 95% were Caucasian,76/1364 had FM. Median LIT (Q1, Q3) was 25 (10,46.3). LIT scores were significantly different among T2T categories (table 1). Significant relevant differences were not evident between RONT and LDAS groups: 1) RONT had greater medication use than LDAS (prednisone 5–10 mg/day use of 17.2% vs 8.3%)). 2) In LDAS, mean SLEDAI was 2, which can occur without clinical DA. RONT thus fared slightly worse than LDAS in patients evaluation of SLE impact. LIT was able to differentiate between T2T outcomes, and the scores moved in the anticipated direction. Though LIT scores for RONT were lower than NO in those with FM, they did not reach significance. This could potentially be secondary to small number of FM patients and use of 4 comparator categories. Conclusions LIT can differentiate between T2T outcomes in SLE patients with and without FM. Given its extensive validation in various languages, regions, measurement equivalence, ease of use, acceptability by patients and physicians, and responsiveness to changes in assessments by physician (SLEDAI, PGA, SRI, T2T) and patient (HRQOL, SLAQ), the tool is indicated for routine patient care, research and clinical trials. Funding Source(s): None

Introduction Anterior uveitis is the most common type of intraocular inflammation. Those associated to HLA-B27 represent 18 to 32% of all anterior uveitis cases. Objectives To describe clinical characteristics, systemic treatment need, and frequency and type of ocular complications in a cohort of patients diagnosed with HLAB27-related anterior uveitis and in a cohort of patients diagnosed with HLA-B27 non-related anterior uveitis. To establish if statistically significant differences between both cohorts exist. Material and methods We performed a retrospective cohort study including patients with non infectious anterior uveitis related and not related to the antigen HLA-B27. Results 162 patients were included, 58 diagnosed with HLA-B27-related anterior uveitis (cohort HLA-B27+1) and 104 diagnosed with HLA-B27-non related anterior uveitis (cohort HLA-B27−). No statistically significant differences were found regarding clinical characteristics between both cohorts with the exception of a higher frequency of recurrences in cohort HLA-B27+ and a higher frequency of chronic uveitis in cohort HLA-B27−. No differences were found regarding systemic treatment use nor development of ocular complications. Discussion In contrast to previous studies, we neither found higher male gender predominance in the cohort of patients with HLA-B27-related anterior uveitis, nor did we find differences regarding average age, laterality, development of complications nor use of systemic corticosteroids.

Resumen Introduccion La uveitis anterior es la forma mas frecuente de inflamacion intraocular. Las formas asociadas al antigeno HLA-B27 suponen entre un 18 y un 32% de los casos de uveitis anterior. Objetivos Describir las caracteristicas clinicas, la necesidad de tratamiento sistemico y la frecuencia y el tipo de complicaciones oculares de una cohorte de pacientes con uveitis anterior asociada a HLA-B27 y de una cohorte de pacientes con uveitis anterior no asociada a HLA-B27. Establecer si existen diferencias entre ambas cohortes. Material y metodos Se realiza un estudio de cohortes retrospectivo descriptivo con componentes analiticos incluyendo a pacientes con uveitis anterior endogena no infecciosa asociada y no asociada a HLA-B27. Resultados Se incluye un total de 162 pacientes, 58 con uveitis anterior asociada a HLAB27 (cohorte HLA-B27+) y 104 con uveitis anterior no asociada a HLA-B27 (cohorte HLA-B27–). No se aprecian diferencias estadisticamente significativas en las caracteristicas clinicas de ambas cohortes a excepcion de una mayor tendencia a la recurrencia en la cohorte HLA-B27+ y una mayor tendencia a la cronicidad en la cohorte HLA-B27–. Tampoco se aprecian diferencias en cuanto al uso de tratamiento sistemico ni al desarrollo de complicaciones oculares de forma global. Conclusiones A diferencia de lo descrito con anterioridad, en este trabajo no encontramos un mayor predominio masculino en la cohorte de uveitis asociada a HLA-B27. Tampoco se aprecian diferencias en edad media, lateralidad, presencia de complicaciones ni frecuencia de uso de corticoides sistemicos.

Objectives There is no updated information on epidemiology and cost of management of non infectious uveitis (NIU) in Spain. This study assessed the frequency of various types of uveitis as well as associated costs of resources used in their management. Material and method NIU epidemiological data and direct costs were collected from a literature search. This was complemented with consensus information from 2 expert panel meetings and data from questionnaires to ophthalmologists and rheumatologists, experts on these conditions. Healthcare resources costs were obtained from the Oblikue database, from a medical society and from approved drug prices in Spain. Results During 2011 the estimate number of NIU was 9398 (45% male, 70% aged 16–65 years). Incidence per type of uveitis was: acute anterior uveitis (AAU) 55%; posterior uveitis (PU) and pan-uveitis (PanU) 15% each; adult chronic anterior uveitis, pediatric chronic anterior uveitis and intermediate uveitis 5% each. Among total costs (77,834,282.10€), initial drug therapy was the highest (43,602,359.29€), followed by surgical treatment of complications (8,367,420.43€). With respect to types of uveitis, PanU (26,692,948.29€), PU (22,283,330.50€) and AAU (14,336,755.38€) showed the highest associated costs. Conclusions Non infectious uveitis is associated to high costs in Spain, both in its diagnosis and in its treatment. Early diagnosis and treatment should allow for substantial savings for the National Health System.

OBJECTIVE: To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience.; METHODS: A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no).; RESULTS: The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management.; CONCLUSIONS: The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade. Copyright © 2018 Elsevier Espana, S.L.U. and Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors.In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295.Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4-45·2]; p0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1-39.8]; p0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported.Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab.Eli Lilly and Company.

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 judgement; (2) prioritisation 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 prioritised. 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.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the receptor for IL-6, approved for the treatment of rheumatoid arthritis (RA) in Japan, Europe and the US. Wide clinical development has shown the efficacy of TCZ in most of the possible situations of RA: RA without prior failure to MTX (AMBITION), RA unresponsive to MTX (SATORI, OPTION, LITHE) or any DMARD (TOWARD, ROSE) as well as RA refractory to anti-TNFa agents (RADIATE). In addition to its early onset, efficacy was constant and even increased as time passed (GROWTH95, GROWTH96). TCZ has shown great efficacy in correcting laboratory alterations in RA, both in acute phase reactants as well as anemia of inflammatory disease. Although in RA TCZ us initially indicated in combination with MTX, it has also shown its efficacy as monotherapy (AMBITION). TCZ is equally effective in the prevention of structural damage (SAMURAI, LITHE). In addition, it has shown to be a safe and well-tolerated drug, similar to other biologic therapies. All of these aspects make TCZ an adequate therapeutic alternative to be considered in any RA scenario.

Objectives. To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. Methods. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Results. Three damage clusters were identified. Cluster (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 10096 in clusters 2 and 3. P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 0.096 of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. Conclusion. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

Anti-tumour necrosis factor-alpha (TNF-α) agents are effective drugs used in several chronic inflammatory diseases such as rheumatoid arthritis (RA). Psoriasiform lesions, including palmoplantar pustulosis, have been described following anti-TNF-α therapy. These lesions often resolve with topical therapy with or without discontinuation of these drugs. However, in some cases, psoriasiform lesions may persist despite anti-TNF-α withdrawal. We report on two RA patients treated with adalimumab (ADA) who developed palmoplantar pustular despite dermatological treatment and ADA discontinuation. Tocilizumab (TCZ) therapy was initiated because of persistence of skin lesions and flare of the disease. Following treatment with this drug, complete resolution of the dermatological lesions and induction of remission of RA was achieved. To the best of our knowledge, management of palmoplantar pustulosis due to TNF-α agents with TCZ leading to both improvement of the disease and resolution of the cutaneous lesions has not previously been reported.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the receptor for IL-6, approved for the treatment of rheumatoid arthritis (RA) in Japan, Europe and the US. Wide clinical development has shown the efficacy of TCZ in most of the possible situations of RA: RA without prior failure to MTX (AMBITION), RA unresponsive to MTX (SATORI, OPTION, LITHE) or any DMARD (TOWARD, ROSE) as well as RA refractory to anti-TNFa agents (RADIATE). In addition to its early onset, efficacy was constant and even increased as time passed (GROWTH95, GROWTH96). TCZ has shown great efficacy in correcting laboratory alterations in RA, both in acute phase reactants as well as anemia of inflammatory disease. Although in RA TCZ us initially indicated in combination with MTX, it has also shown its efficacy as monotherapy (AMBITION). TCZ is equally effective in the prevention of structural damage (SAMURAI, LITHE). In addition, it has shown to be a safe and well-tolerated drug, similar to other biologic therapies. All of these aspects make TCZ an adequate therapeutic alternative to be considered in any RA scenario.

Tocilizumab (TCZ) is a humanized monoclonal antibody which targets the receptor for IL-6, developed by the Japanese pharmaceutical company Chugai and the Swiss company Roche. In Japan it is already under use for Castleman's disease, rheumatoid arthritis (RA), and juvenile idiopathic arthritis. The clinical development outside Japan is very extensive and has shown efficacy in possible RA scenarios; early RA (part of the AMBITION study), established, MTX-resistant RA (OPTION) and RA resistant to other DMARD (TOWARD), and anti-TNF-α resistant RA (RADIATE). Both monotherapy with TCZ (AMBITION) and associated to other background drugs. Radiological efficacy has also been proven (LITHE). So TCZ is probably the biologic therapy with the most extensive clinical development before marketing in the western hemisphere. In this review we will specifically deal with clinical and radiological efficacy, as wel as its safety profile.