Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors.

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

Improvement of Disease Management and Cost Effectiveness in Chinese Patients with Ankylosing Spondylitis Using a Smart-Phone Management System: A Prospective Cohort Study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic disease that decreases mobility, function, and quality of life. This study introduced the "Smart-phone SpondyloArthritis Management System" (SpAMS), an interactive mobile health (mHealth) tool designed for AS/spondyloarthritis (SpA) disease management and used SpAMS data to evaluate clinical characteristics of Chinese patients with AS. METHODS: SpAMS integrates patient's and physician's portals in a smart phone application. The Chinese Ankylosing Spondylitis Prospective Imaging Cohort was launched using SpAMS in April 2016. Patient self-assessments were completed online at baseline and at every subsequent clinic visit. Physician-reported assessments and treatments were recorded by rheumatologists during each visit. RESULTS: In total, 1201 patients with AS [mean (SD) age, 30.6 (8.7) years; male, 82.6%] were recruited. Mean (SD) disease duration was 8.4 (6.1) years. Past or current symptoms of acute anterior uveitis (AAU), psoriasis, and inflammatory bowel disease (IBD) were observed in 21.0%, 3.7%, and 9.4% of patients, respectively. AAU and IBD occurred significantly more in patients with symptom duration > 10 years. The most commonly used medications at baseline were nonsteroidal anti-inflammatory drugs (98.2%). Patients using tumour necrosis factor inhibitors accounted for 20.8%, and 66.4% of patients used conventional synthetic disease-modifying antirheumatic drugs. At baseline, 57.2% of patients had inactive disease (ID)/low disease activity (LDA); this rate significantly improved to 79.2% after a mean follow-up of 13.3 (5.9) months. Compared with relapsed patients, new achievers of ID/LDA underwent more online patient assessments (P < .001). Problems solved in SpAMS caused 29.1% of clinic visits to a tertiary hospital unnecessary. SpAMS saved an average of 5.3 hours and 327.4 RMB per person on traffic expenses; these expenses equalled 16% of the Chinese monthly disposable personal income. CONCLUSIONS: SpAMS is a time- and cost-saving disease management tool that can help patients with AS perform self-management and provide valuable data to clinicians.

First-degree relatives of axial spondyloarthritis patients of the pre-SpA cohort would consider using medication in a preventive setting.

To study the willingness of first-degree relatives of axial spondyloarthritis (axSpA) patients to use preventive medication. First-degree relatives of HLA-B27-positive axSpA patients (pre-SpA cohort) (n = 106) completed a survey including scenarios varying in disease risk, side effects, and treatment effect of hypothetical preventive medication and questions about their perceived risk of developing SpA and assessment of the severity of SpA. The willingness to use preventive medication was 63.2-91.5% (with 30-70% SpA risk, respectively) and declined to 27.4-51.9% respectively, when side effects might occur. On a visual analogue scale (VAS) 0-100 mm (totally disagree-totally agree) (median;range), participants were not occupied by the thought of developing SpA (23;13-39), did not assume that they will eventually develop SpA (22;14-35), and consider SpA a severe disease (66;52-78). The willingness to use preventive medication was negatively influenced by their own risk assessment of developing SpA (OR = 1.17, p = .001) and was not primarily influenced by costs and route of administration. First-degree relatives of axSpA patients with a clearly increased disease risk (70%) would largely consider using preventive medication. Their willingness roughly halved by the possible occurrence of side effects. Participants' perceived risk to develop SpA and their assessment of the severity of SpA negatively influenced the willingness to use preventive medication.

Association study between killer immunoglobulin-like receptor polymorphisms and ankylosing spondylitis disease: An updated meta-analysis.

BACKGROUND: Several genetic studies have assessed the association between polymorphisms in killer immunoglobulin-like receptors (KIR) genes and susceptibility of individuals to ankylosing spondylitis (AS), but the findings have been inconclusive and incongruous. Therefore, we conducted this meta-analysis of all case-control studies meeting the inclusion criteria for obtaining an exact conclusion of the effect of KIR polymorphisms on the risk of AS. METHODS: A systematic literature search was conducted in electronic databases, including Scopus web of science, ScienceDirect, and PubMed to find all eligible studies exploring the association between KIR polymorphisms and the risk of AS, prior to June 2017. Pooled odds ratios (OR) and their corresponding 95% CIs were used to evaluate the strength of the association between KIR polymorphisms and the risk of AS. RESULTS: A total of 16 case-control studies, encompassed in 12 papers, with 1770 cases and 2907 healthy subjects were included in the meta-analysis. This meta-analysis revealed three significant positive associations of 2DS1, 2DS5, and 3DS1 with susceptibility to AS, while two significant negative associations of 2DL2 and 2DS2 with susceptibility to AS were identified. In the subgroup analysis based on human leukocyte antigen (HLA)-B*27 positive patients and healthy subjects, results indicated that there were four significant positive associations between 2DL5, 2DS4, 2DS5, 3DS1 polymorphisms and susceptibility to AS in HLA-B*27-positive patients; a significant negative association of 3DL1 in HLA-B*27-positive patients was found. CONCLUSIONS: While 2DS1, 2DS5, and 3DS1 polymorphisms increased AS risk, 2DL2 and 2DS2 polymorphisms were associated with reduced AS susceptibility.

Exercise habits and C-reactive protein may predict development of spinal immobility in patients with ankylosing spondylitis.

To assess predictors for spinal immobility in a long-term clinical study of patients with AS, data from annual clinical measurements of spinal mobility in 54 patients (41 men, mean of age at end of follow-up 54.7 years) with ankylosing spondylitis were co-analysed with data regarding lifestyle factors as well as laboratory measurements from a previous cross-sectional study. Spinal immobility was graded on the basis of recently published age-, sex- and length-specific reference intervals. Exercise habits and high-sensitivity C-reactive protein (hsCRP) were independently associated with the development of subnormal spinal immobility (p = 0.019 and p = 0.021). In multiple regression models, approximately 25% of the spinal immobility could be attributed to disease duration (p ≤ 0.011), levels of hsCRP (p ≤ 0.004) and exercise in leisure time (p ≤ 0.019). The mean concentration of hsCRP was 4.2 mg/L (range 0.2-8.4 mg/L) in the study cohort. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and physical activity at work were not associated with spinal immobility. The results indicate that exercise habits may have an impact in preventing the development of spinal immobility in AS independently of disease duration and inflammation. This corresponds well with the accumulated knowledge from long-term clinical experience among rheumatologists, health professionals and patients. Consequently, exercise should remain an important part of the non-pharmacological treatment and self-care for patients with AS. Furthermore, modest inflammatory activity, measured as a slightly elevated hsCRP concentration, appears to affect subsequent spinal immobility in AS.

The Protective Effect of Chrysanthemum indicum Extract against Ankylosing Spondylitis in Mouse Models.

In traditional Chinese and Korean homeopathic medicine, Chrysanthemum indicum Linné (Asteraceae) is a time-honored herb, prescribed for the resolution of symptoms associated with inflammatory and hypertensive conditions as well as those affecting the lungs and its associated structures. The goal of this work is to investigate the defensive role of Chrysanthemum indicum extract in fighting ankylosing spondylitis (AS) using mouse models, through which the manifestation and extent of the disease progression were measured with quantitative analysis of the intervertebral joints. Markers of inflammation as well as oxidative stress were also analysed. Western blot was used to quantify the levels of Nuclear Factor-κB (NF-κB) p65, Dickkopf-1 (DKK-1), and sclerostin (SOST). Consequently, the findings of this experiment demonstrated that AS in mice that were given Chrysanthemum indicum extract had lower level of TNF-α, IL-1ß, and IL-6 (P < 0.05) and increased level of catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) (P < 0.05). The results also revealed that Chrysanthemum indicum supplemented with diet contributed to a decrease in Nuclear Factor-κB (NF-κB) p65 protein expression (P < 0.05) and higher levels of DKK-1 and SOST proteins (P < 0.05). Therefore, we concluded that the beneficial role of Chrysanthemum indicum in AS is manifested through downregulating oxidative stress, inhibiting inflammatory mediators and NF-κB, and increasing DKK-1 and SOST levels.

Structural Disease Progression in Axial Spondyloarthritis: Still a Cause for Concern?

PURPOSE OF THE REVIEW: Progressive ankylosis is a feared consequence of long-standing axial spondyloarthritis. We aim to critically review current insights into the effect of therapy, the molecular pathways involved in this process, and to present a model explaining the sequence of events. RECENT FINDINGS: Long-term follow-up data suggest that successful control of inflammation may slow down radiographic progression of disease in axial spondyloarthritis. Structural effects of new therapies such as interleukin-17 targeting need to be further studied. Bone loss and architectural changes could act as driver for the tissue remodeling process trying to maintain spinal stability in the presence of inflammation. Despite some progress, the nature and mechanisms of new bone formation in axial spondyloarthritis still remain incompletely understood. However, long-term control of inflammation appears critical to avoid progressive disability due to structural damage.

Inflammatory Arthritis Prevalence and Health Services Use in the First Nations and Non-First Nations Populations of Alberta, Canada.

OBJECTIVE: To estimate prevalence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic disease (PsD), and crystal-related arthritis and health care use for inflammatory arthritis in First Nations and non-First Nations patients in Alberta, Canada. METHODS: Population-based cohorts of adults with RA, AS, PsD, and crystal-related arthritis were defined, with First Nations determination by premium payer status, to estimate prevalence rates. Rates of outpatient primary care, specialist visits, and hospitalizations (all-cause, inflammatory-arthritis specific) were estimated. RESULTS: RA affected 3 times as many First Nations residents compared to non-First Nations residents (standardized rate ratio [SRR] 3.2, 95% confidence interval [95% CI] 2.9-3.4). AS and PsD were more prevalent in First Nations (AS 0.6 per 100 residents; SRR 2.7, 95% CI 2.3-3.2 and PsD 0.3 per 100 residents; SRR 1.5, 95% CI 1.3-1.9), whereas crystal-related arthritis was less prevalent (SRR 0.7, 95% CI 0.6-0.7). First Nations patients were more likely to have primary care visits (SRR 1.7, 95% CI 1.6-1.8) and less likely to have specialist visits (SRR 0.6, 95% CI 0.6-0.7) for RA relative to non-First Nations individuals. In PsD and crystal-related arthritis, First Nations people had higher rates of cause-specific hospitalizations. CONCLUSION: The estimated prevalence of RA, AS, and PsD was higher in the First Nations population, while crystal-related arthritis was less prevalent compared to the non-First Nations population. First Nations people were more likely to see primary care physicians and were less likely to see specialists for inflammatory arthritis care.

Patients with ankylosing spondylitis have been breast fed less often than healthy controls: a case-control retrospective study.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and pelvis of young adults. On the HLA-B27 genetic background, the occurrence of AS is influenced by the intestinal microbiota. The goal of our study was to test whether breast feeding, which influences microbiota, can prevent the development of AS. METHODS: First, 203 patients with HLA-B27-positive AS fulfilling the modified New York criteria were recruited in the Department of Rheumatology, Ste Marguerite hospital in Marseilles. A total of 293 healthy siblings were also recruited to make up a control group within the same families. Second, 280 healthy controls, and 100 patients with rheumatoid arthritis and their siblings were recruited. The data collected were age, gender, number of brothers and sisters, age at disease onset, type and duration of feeding (breast or bottle). RESULTS: Patients with AS had been breast fed less often than healthy controls. In families where children were breast fed, the patients with AS were less often breast fed than their healthy siblings (57% vs 72%), giving an OR for AS onset of 0.53 (95% CI (0.36 to 0.77), p value=0.0009). Breast feeding reduced familial prevalence of AS. The frequency of breast feeding was similar in the AS siblings and in the 280 unrelated controls. However, patients with AS were less often breast fed compared with the 280 unrelated controls (OR 0.6, 95% CI (0.42 to 0.89), p<0.01). CONCLUSIONS: Our study suggests a breastfeeding-induced protective effect on the occurrence of AS. To our knowledge, this is the first study of breastfeeding history in patients with AS.

Nuevos paradigmas en el diagnóstico y la clasificación de las espondiloartritis / No disponible

No disponible

Diferente expresión clínica de los pacientes con espondilitis anquilosante según el sexo en función del tiempo de evolución. Datos de REGISPONSER / Different clinical expression of patients with ankylosing spondylitis according to gender in relation to time since onset of disease. Data from REGISPONSER

Objetivo. Establecer las características diferenciales según el sexo y el tiempo de evolución de la enfermedad en aquellos pacientes diagnosticados de espondilitis anquilosante (EA) asistidos en consultas de reumatología de toda España, incluidos en el Registro Español de Espondiloartritis (REGISPONSER), así como la repercusión diagnóstica y terapéutica que ello conlleva. Pacientes y métodos. Estudio transversal y observacional de 1.514 pacientes con EA seleccionados de entre 2.367 con espondiloartritis incluidos en REGISPONSER. En cada paciente se evaluaron y registraron de modo exhaustivo los datos demográficos, epidemiológicos, sociosanitarios, clínicos, analíticos, radiológicos y terapéuticos previstos en el protocolo de REGISPONSER que componen el Conjunto Mínimo Básico que identifica la enfermedad. La función física se evaluó mediante «Bath Ankylosing Spondylitis Functional Index». La actividad clínica mediante velocidad de sedimentación globular, proteína C reactiva y «Bath Ankylosing Spondylitis Disease Activity Index» (BASDAI). A cada paciente se le realizaron radiografías anteroposterior de pelvis, anteroposterior y lateral de columna lumbar y lateral de columna cervical, y se puntuaron según el índice «Bath Ankylosing Spondylitis Radiographic Index Spine» (BASRI-Spine), que mide el daño estructural. Resultados. De los 1.514 pacientes seleccionados, 1.131 (74.7%) eran hombres. Encontramos que existen diferencias significativas en la edad tanto al inicio de los síntomas como en el día de la inclusión entre ambos grupos, siendo menor en los hombres. También obtuvimos diferencias en el tiempo de evolución de la enfermedad, que fue menor en el grupo de las mujeres. En cuanto a la existencia de antecedentes de EA entre los familiares de primer grado, las formas familiares fueron más frecuentes entre las mujeres, también resultó superior en éstas la puntuación media del BASDAI, con independencia del tiempo de evolución. Por el contrario, la mejoría del dolor con la toma de antiinflamatorios no esteroideos fue mayor en el caso de los hombres, así como la severidad radiológica, ambas de forma significativa. Conclusiones. Entre los pacientes con EA españoles existen algunas diferencias en las manifestaciones clínicas y cuando se controló según el tiempo de evolución, también encontramos diferencias radiológicas según el sexo; los hombres muestran más daño estructural, mientras que las mujeres presentan mayor actividad. Estos datos sugieren que el fenotipo de EA difiere entre géneros, lo que puede influir en el manejo diagnóstico y posterior elección terapéutica (AU)

Objective. To describe the differential characteristics by gender and time since disease onset in patients diagnosed with ankylosing spondylitis (AS) attending the Spanish rheumatology clinics, including those on the “Spanish Registry of spondyloarthritis” (REGISPONSER), as well as the diagnostic and therapeutic implications that this entails. Patients and methods. This is a transversal and observational study of 1514 patients with AS selected from 2367 spondyloarthritis cases included in REGISPONSER. For each patient, the demographics, epidemiology, geriatric, clinical, laboratory, radiological, and therapeutic aspects were evaluated and comprehensively recorded under the aegis of REGISPONSER, constituting the Minimum Basic identifying data for the disease. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical activity was evaluated using erythrocyte sedimentation rate, C reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Each patient underwent pelvic anteroposterior, anteroposterior and lateral lumbar spine as well as lateral cervical spine X-ray; they were scored according to the Bath Ankylosing Spondylitis Spine Radiographic Index, which measures structural damage. Results. Of the 1514 patients screened, 1131 (74.7%) were men. We found significant differences in age at onset of symptoms as well as in the day of inclusion, between the two groups, being lower in men. We also obtained differences in the duration of the disease, which was lower in women. As for the existence of a history of AS among first-degree relatives, family forms were more common among women. The mean BASDAI score was also higher in women, regardless of time since onset of disease. In contrast, the improvement of pain with the use of NSAID's and radiological severity were higher in men, both reaching statistical significance. Conclusions. Among the Spanish AS patients, there are some differences in the clinical manifestations, even when the time since onset of disease was controlled; we also found radiological differences by gender; men showing more structural damage, while women were more active. These data suggest that the phenotype of AS differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions (AU)

Lipopolysaccharide treatment suppresses spontaneously developing ankylosing enthesopathy in B10.BR male mice: the potential role of interleukin-10.

BACKGROUND: Ankylosing enthesopathy (ANKENT) is an animal model of human ankylosing spondylitis. ANKENT is an inflammatory disease affecting the ankle and tarsal joints of the hind limbs in susceptible mouse strains. In the disease, the participation of intestinal microbiota components was suggested. Therefore, we attempted to increase the incidence of ANKENT by systemic administration of lipopolysaccharide (LPS), which is a component of bacterial cellular walls and stimulates inflammatory processes. METHODS: ANKENT occurrence, serum cytokine profiles, spleen cellular composition and in vitro cytokine response to LPS were analysed in LPS-treated and control LPS-untreated B10.BR male mice. RESULTS: Contrary to expectations, LPS treatment decreased the incidence of ANKENT in LPS-treated group compared to control LPS-untreated group. Flow cytometry analysis of splenocytes showed an increased percentage of macrophages, dendritic cells and neutrophils and a decreased percentage of B cells, T cells and T helper cells in LPS-treated males following LPS administration. In addition, LPS-treated males had significantly elevated IL-6 and IL-10 serum levels. At 20-22 weeks after the final LPS application, splenocytes from LPS-treated mice were more susceptible to in vitro LPS stimulation than those of the controls and produced significantly higher levels of TNFα and IL-6. CONCLUSIONS: Repeated systemic stimulation with microbial component lipopolysaccharide in early adulthood significantly reduced the incidence of ANKENT in B10.BR mice and this finding can support the "hygiene hypothesis". In LPS-treated mice, the innate immunity parameters and the level of anti-inflammatory IL-10 cytokine were significantly increased. Nevertheless, the immunological mechanism of the LPS protective effect remains unclear.

Does HLA-B*2706 protect against ankylosing spondylitis? A meta-analysis.

The human leukocyte antigen (HLA)-B*2706 is a relatively rare subtype of HLA-B27. In contrast to most HLA-B27 subtypes, some studies have reported HLA-B*2706 to be protective against ankylosing spondylitis (AS). A systematic review and a meta-analysis of available studies was performed to investigate the association of HLA-B*2706 with AS. After literature review a random effect meta-analysis was performed. No studies were found comparing the frequency of HLA-B*2706 in AS patients and controls. Meta-analysis of seven studies using HLA-B27-positive AS patients and controls showed a protective effect of HLA-B*2706 on development of AS in HLA-B27 individuals (odds ratio = 0.128, 95% CI = 0.043-0.378, P < 0.001). The results of the meta-analysis of HLA-B*2706 in HLA-B27-positive patients and controls is preliminary evidence of a protective effect of HLA-B*2706 against AS in the population. There is a clear need for additional studies on HLA-B*2706 in AS. Due to the fact that HLA-B*2706 is more or less restricted to Southeast Asia, researchers in this part of the world may have an essential role in performing these studies.

Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis.

Up to now, many publications have evaluated the correlation between IL-23R polymorphisms and ankylosing spondylitis with conflicting results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of IL-23R polymorphisms with AS. Relevant published data were retrieved through Medline, PubMed, Embase, Web of Science, CNKI, Chinese BioMedical Literature Database on disc, and the statistical analysis was conducted using Stata 11.0. (1) A total of 11 literatures, including 13 population samples, were studied. (2) The allele A frequency of rs11209032 was higher in the AS group than in the controls (A vs. G: OR = 1.173, 95% CI = 1.107-1.243, P < 0.001). (3) The allele A of rs1004819 was higher in the AS group than in the controls in both all-pooled population (A vs. G: OR = 1.147, 95% CI = 1.022-1.287, P = 0.02) and Europe-pooled population (A vs. G: OR = 1.199, 95% CI = 1.007-1.429, P = 0.042). (4) The allele frequency T of rs1343151, G of rs10489629, and A of rs11209026 was lower in the AS group than in the controls. (5) No significant differences were found in allele frequency of rs10889677 polymorphism between cases and controls by random effects model. We concluded that the genetic susceptibility for AS is associated with the IL-23R gene polymorphisms. The protective SNPs include rs1343151, rs10489629, and rs11209026 while rs1004819 and rs11209032 may be the susceptibility SNPs.

Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.

Dendritic cells (DCs), which are known to support immune activation during infection, may also regulate immune homeostasis in resting animals. Here we show that mice lacking the ubiquitin-editing molecule A20 specifically in DCs spontaneously showed DC activation and population expansion of activated T cells. Analysis of DC-specific epistasis in compound mice lacking both A20 and the signaling adaptor MyD88 specifically in DCs showed that A20 restricted both MyD88-independent signals, which drive activation of DCs and T cells, and MyD88-dependent signals, which drive population expansion of T cells. In addition, mice lacking A20 specifically in DCs spontaneously developed lymphocyte-dependent colitis, seronegative ankylosing arthritis and enthesitis, conditions stereotypical of human inflammatory bowel disease (IBD). Our findings indicate that DCs need A20 to preserve immune quiescence and suggest that A20-dependent DC functions may underlie IBD and IBD-associated arthritides.

Documento SER de consenso sobre el uso de terapias biológicas en la espondilitis anquilosante y otras espondiloartritis, excepto la artritis psoriásica / Consensus statement of the Spanish Society of Rheumatology on the management of biologic therapies in spondyloarthritis except for psoriatic arthritis

Objetivo. Dada la gran cantidad de información sobre las terapias biológicas (TB) en las espondiloartritis (EspA), excepto la artritis psoriásica (APs), y la variabilidad en cuanto a su calidad, desde la Sociedad Española de Reumatología (SER) se ha impulsado la generación de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatólogos e implicados en el tratamiento de estos pacientes. Métodos. Las recomendaciones se emitieron siguiendo la metodología de grupos nominales. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Resultados. Se realizan recomendaciones sobre el uso de las TB para el tratamiento de las EspA (excepto la APs). Incluyen la evaluación de la enfermedad, objetivos del tratamiento, esquema terapéutico y cambios en éste. Conclusiones. Se presentan las actualizaciones a las recomendaciones SER para el uso de TB en pacientes con EsA, excepto la APs(AU)

Objective. Due to the amount and variability in quality regarding the use of biologic therapy (BT) in patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA) patients, the Spanish Society of Rheumatology has promoted the generation of recommendations based on the best evidence available. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA), who are using, or about to use BT. Methods. Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Results. We have produced recommendations on the use of BT currently available for SpA (but not PsA) in our country. These recommendations include disease assessment, treatment objectives, therapeutic scheme and switching. Conclusions. We present an update on the SER recommendations for the use of BT in patients with SpA, except for PsA(AU)

Evidence for the prevention of enthesitis in HLA-B27/hß(2)m transgenic rats treated with a monoclonal antibody against TNF-α.

Transgenic rats with high expression of HLA-B27 and human ß(2) -microglobulin (B27TR) develop a multisystem inflammatory disease resembling human inflammatory bowel disease (IBD) and spondyloarthropaties (SpA). Tumour necrosis factor α (TNF-α) has a crucial role in sustaining chronic inflammation in the gut and joints. The aim of this work was to evaluate whether TNF-α blockade could prevent or reduce the inflammation of peripheral joints in B27TR. A first group of 9-week-old B27TR received an anti-TNF-α monoclonal antibody (mAb) or an isotypic IgG2a,k up to the age of 18 weeks. An untreated group was monitored up to the age of 18 weeks and then randomly assigned to a 9-week treatment with anti-TNF-α mAb or IgG2a,k. Each rat was monitored for clinical IBD and peripheral joint manifestations. After sacrifice the colon and hind paws were examined for macroscopical and microscopical pathological changes. Early TNF-α blockade prevented, and late treatment improved IBD signs in B27TR. Erythema, oedema, inflammatory infiltrate close to the tendons and enthesis, proliferating chondrocyte-like cells, signs of new endochondral bone ossification and bone erosion were observed in peripheral joints of four out of six IgG2a,k-treated B27TR, both at 18 and 27 weeks. Immunopositivity for phosphorylated Smad1/5/8 indicated that the process of joint remodelling was activated in B27TR. Some entheses showed chondroid nodules. Anti-TNF-α treatment reduced inflammation and preserved the enthesis organization in most animals. Occasional and transient erythema and oedema were still present in three of six of the late anti-TNF-α-treated animals. Smad1/5/8 signalling was not inhibited by late anti-TNF-α treatment. In B27TR, articular involvement follows IBD onset and develops at entheses. Early TNF-α blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.

Can we stop progression of ankylosing spondylitis?

Ankylosing spondylitis is characterised by inflammation of the spine and the entheses followed by bone formation. Excessive bone formation in ankylosing spondylitis leads to the formation of bone spurs, such as syndesmophytes and enthesiophytes, which contribute to ankylosis of joints and poor physical function. This process is based on increased differentiation of osteoblasts from their mesenchymal precursors, which allows to rapidly build up new bone. Prostaglandins, bone morphogenic proteins and Wnt proteins play an essential role in this process. By contrast, tumour necrosis factor (TNF) does not appear to be the direct trigger for osteophyte formation in ankylosing spondylitis. The article reviews the current knowledge regarding the mechanisms and clinical role of ankylosis and explains strategies on how to prevent it in patients with ankylosing spondylitis.

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab.

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 +/- 1.7 and that in the physician's global assessment was 4.4 +/- 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (+/- 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.