Treatment of giant cell arteritis.

Giant cell arteritis (GCA) is the most common form of vasculitis in adults. Cranial manifestations are typical clinical features of this vasculitis. Sometimes the presenting symptoms are nonspecific and, in some cases, large-vessel involvement may prevail. Polymyalgia rheumatica is a frequent manifestation that in some cases may be the presenting symptom of GCA. Visual complications, in particular the risk of blindness, constitute the most feared manifestations of GCA. Prompt recognition of this vasculitis is required to avoid irreversible complications. Prednisone/prednisolone at a dose of 40-60 mg/day is the cornerstone therapy in GCA. Glucocorticoids lead to rapid improvement of symptoms and may reduce the risk of irreversible visual loss. However, relapses are common when the prednisone dose is tapered. Therefore, additional therapies are required in relapsing GCA or when a rapid reduction of glucocorticoids is needed. The most widely used conventional immunosuppressive drug is methotrexate Adjunctive treatment with methotrexate may decrease the risk of relapses and reduce glucocorticoid exposure. However, comprehensive reviews indicate that the efficacy of methotrexate in GCA is modest. The experience with other conventional immunosuppressive drugs in GCA patients is scarce. In some cases, the new biologic agents are required. Among them, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody tocilizumab. It improves clinical symptoms, reduce the cumulative prednisone dose and the frequency of relapses in GCA patients. However, anti-tumor necrosis factor-α therapy is not useful in GCA. Promising results on other biologic agents, such as abatacept, ustekinumab or anakinra, require further confirmatory studies.

The role of biologics in the treatment of giant cell arteritis.

INTRODUCTION: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects individuals older than 50 years. Although glucocorticoids remain the mainstay in the treatment of this vasculitis, other drugs are often required to achieve clinical remission and allow glucocorticoid discontinuation. AREAS COVERED: The review summarizes the main biologic therapies used for the managements of GCA. EXPERT OPINION: Although several biologic agents have been used in patients with GCA, the only biologic agent currently approved for this purpose is the recombinant humanized anti-IL-6 receptor antibody: tocilizumab. It has demonstrated efficacy to improve clinical symptoms, decrease the cumulative prednisone dose and reduce the frequency of relapses in clinical trials and real-life studies on patients with GCA. A trial showed that abatacept may be useful to maintain remission in GCA patients. An open-label study suggested that ustekinumab could be useful for the treatment of patients with refractory GCA. However, further studies are required to confirm if both abatacept and ustekinumab are useful as an adjunctive therapy to reduce relapses or as a glucocorticoid-sparing agent in GCA. Anakinra has been successfully used in a few patients with refractory GCA. In contrast, antitumor necrosis factor-α therapy yielded disappointing results in GCA.

Detection of high cardiovascular risk patients with ankylosing spondylitis based on the assessment of abdominal aortic calcium as compared to carotid ultrasound.

BACKGROUND: This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. METHODS: A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. RESULTS: Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE ≥ 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r2 = 0.49, p < 0.001). CONCLUSIONS: A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease.

Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update.

INTRODUCTION: Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse. AREAS COVERED: This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR. EXPERT OPINION: In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5-25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.

Current and emerging diagnosis tools and therapeutics for giant cell arteritis.

INTRODUCTION: Giant cell arteritis (GCA) is the most common large-vessel vasculitis in individuals older than 50 years from Western countries. The goal of the treatment is to achieve improvement of symptoms and clinical remission as well as decrease the risk of severe vascular complications. Areas covered: The review summarizes the main epidemiological and clinical features of GCA and discusses in depth both the classic and the new therapies used in the management of GCA. Expert commentary: Prednisone/prednisolone of 40-60 mg/day is the mainstay in GCA therapy. It yields improvement of clinical features and reduces the risk of permanent visual loss in patients with GCA. Other drugs are used in patients who experience relapses (flares of the disease) or side effects related to glucocorticoids. Methotrexate is the most common conventional immunosuppressive drug used as a glucocorticoid sparing agent. Among the new biologic agents, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody, which is effective to improve clinical symptoms, decrease the cumulative prednisone dose, and reduce the frequency of relapses in these patients. Antitumor necrosis factor-α therapy is not useful in GCA. Experience with other biologic agents, such as abatacept or ustekinumab, looks promising but it is still scarce.

Relative Risk Chart Score for the Assessment of the Cardiovascular Risk in Young Patients with Ankylosing Spondylitis.

OBJECTIVE: To determine if the use of the relative risk (RR) chart score may help to identify young ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. METHODS: 73 AS patients younger than 50 years were assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. C-reactive protein (CRP) value at disease diagnosis and carotid ultrasound data were also analyzed. RESULTS: Twenty (27.4%) patients exhibited carotid plaques being classified into the category of very high CV risk. None of them was found to have a high/very high TC-SCORE. CRP > 3 mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, p = 0.03). Whereas only 5 (14.2%) of the 35 patients with RR = 1 had carotid plaques, 15 (39.5%) of 38 with RR > 1 showed plaques. A model that included the performance of carotid US in patients with RR > 1 who had CRP > 3 mg/L allowed us to identify 60% of very high risk patients, with a specificity of 77.4%. CONCLUSIONS: RR chart score assessment may help to identify young AS patients at high risk of CV disease.

IgA Vasculitis: Genetics and Clinical and Therapeutic Management.

PURPOSE OF REVIEW: The purpose of the study is to perform an update on the current knowledge on genetics, clinical manifestations, and therapy in immunoglobulin A vasculitis (IgAV) (Henoch-Schönlein purpura). RECENT FINDINGS: A strong genetic predisposition in individuals with IgAV was confirmed. It was due to the association with the HLA class II region that in people of European background is mainly related to HLA-DRB1*01 allele. Recent reports support the claim that kidney disease is more common in adults than in children with IgAV. The clinical spectrum and outcome of adults with IgAV depends on the age of onset. Relapses are not uncommon in IgAV. The presence of renal impairment or proteinuria excretion exceeding 1 g/24 h at the time of disease diagnosis and the degree of renal damage on the kidney biopsy are the best predictors of end-stage renal failure in adults with IgAV. The levels of urinary IgA at the onset of the disease may predict a poor renal outcome. The use of prednisone does not seem to prevent persistent kidney disease in children with IgAV. No additional benefit of adding cyclophosphamide to glucocorticoids in adults with IgAV was found. Rituximab seems to be a promising therapy in the management of adults with IgAV. In this overview, we focus on the genetics, clinical manifestations, and therapy of IgA vasculitis, emphasizing the main differences in the clinical expression of the disease between children and adults.

Cardiovascular risk stratification in axial spondyloarthritis: carotid ultrasound is more sensitive than coronary artery calcification score to detect high-cardiovascular risk axial spondyloarthritis patients.

OBJECTIVES: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography (US) to detect high cardiovascular (CV) risk axial spondyloarthritis (ax-SpA) patients. METHODS: CACS and carotid plaques were assessed in 66 consecutive ax-SpA patients (51 fulfilling criteria for ankylosing spondylitis and 15 for non-radiological ax-SpA) without history of CV events. The Systematic Coronary Risk Evaluation (SCORE) calculated using total cholesterol (TC-SCORE) was assessed in 64 patients without diabetes mellitus or chronic kidney disease. RESULTS: The mean age of the patients and the median disease duration since the onset of symptoms were 49.3 and 14.5 years. HLA-B27 was positive in 47 (75%) patients. CV risk was categorised according to the TC-SCORE as low (<1%; n=33), moderate (≥1% and<5%; n=30) and high/very high risk (≥5%; n=1). Most patients with low TC-SCORE (27/33; 82%) had normal CACS (zero), and only 1/33 had CACS >100. However, carotid plaques were observed in patients with CACS=0 (12/37; 32%) and CACS 1-100 (10/16; 62%). The sensitivity to detect high/very high CV risk using only the TC-SCORE was very low as the algorithm only detected 1/33 (3%) of patients with high/very high CV risk. Ten of 33 (30%) high/very high CV risk patients were identified using a chart TC-SCORE risk ≥5% plus the presence of CACS ≥100 in patients with moderate TC-SCORE. The replacement of CACS with carotid US identified a higher number of high/very high CV risk patients (22/33; 67%). CONCLUSIONS: Carotid US is more sensitive than CACS for the detection of high CV risk in ax-SpA patients.

Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis.

Several protein tyrosine phosphatase non-receptor 22 (PTPN22) single-nucleotide polymorphisms (SNPs) have been significantly related with rheumatoid arthritis (RA) susceptibility. Nevertheless, its potential influence on PTPN22 expression in RA has not been completely elucidated. Furthermore, PTPN22 binds to C-Src tyrosine kinase (CSK) forming a key complex in autoimmunity. However, the information of CSK gene in RA is scarce. In this study, we analyzed the relative PTPN22 and CSK expression in peripheral blood from 89 RA patients and 43 controls to determine if the most relevant PTPN22 (rs2488457, rs2476601 and rs33996649) and CSK (rs34933034 and rs1378942) polymorphisms may influence on PTPN22 and CSK expression in RA. The association between PTPN22 and CSK expression in RA patients and their clinical characteristics was also evaluated. Our study shows for the first time a marked down-regulation of PTPN22 expression in RA patients carrying the risk alleles of PTPN22 rs2488457 and rs2476601 compared to controls (p = 0.004 and p = 0.007, respectively). Furthermore, CSK expression was significantly lower in RA patients than in controls (p < 0.0001). Interestingly, a reduced PTPN22 expression was disclosed in RA patients with ischemic heart disease (p = 0.009). The transcriptional suppression of this PTPN22/CSK complex may have a noteworthy clinical relevance in RA patients.

A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis.

The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.

Significant sE-Selectin levels reduction after 6 months of anti-TNF-α therapy in non-diabetic patients with moderate-to-severe psoriasis.

PURPOSE: Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNF-α therapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNF-α therapy on these molecules. METHODS: Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA. RESULTS: Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNF-α therapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE-selectin levels significantly reduced after 6 months of therapy (p = .0006). CONCLUSIONS: Metabolic syndrome features are associated with endothelial activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNF-α therapy on mechanisms associated with the development of atherosclerosis in psoriasis.

Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study.

OBJECTIVE: Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. METHODS: Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. RESULTS: 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9-51) and 40 (24%) developed new accompanying features after 19months median (IQR 6-56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68-9.21, p=0.002). CONCLUSION: Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis.

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

Carotid ultrasound in the cardiovascular risk stratification of patients with ankylosing spondylitis: results of a population-based study.

OBJECTIVES: To determine if the use of carotid ultrasonography (US) may improve the cardiovascular (CV) risk stratification in patients with ankylosing spondylitis (AS). METHODS: A set of 127 consecutive patients without history of CV events, diabetes mellitus or chronic kidney disease that fulfilled definitions for AS according to the 1984 modified New York criteria were recruited to assess carotid intima-media thickness and presence of plaques. CV risk was calculated according to the systematic coronary risk evaluation (SCORE), the Framingham Risk Score (FRS) and the Reynolds Risk Score (RRS). RESULTS: Men outnumbered women (61.4%). The mean±SD age at the time of the study was 44.5±11.6 years. The median (interquartile range-IQR) disease duration was 13 (7-22) years. The median (IQR) BASDAI at the time of the study was 3.65 (1.7- 4.9). HLA-B-27 was positive in 77.2%, and syndesmophytes were present in 38.9%. Carotid plaques were found in 43 (33.9%). Regardless of the algorithm used for CV risk stratification, more than 50% of the patients classified as having moderate CV risk had carotid plaques. Moreover, 20.8%, 24.6% and 53.3% of AS that fulfilled the category of low CV risk according to the total cholesterol (TC)-SCORE, FRS and RRS, respectively had carotid plaques. A model that included patients with a chart TC-SCORE ≥5% or TC-SCORE ≥1% <5% plus carotid plaques or TC-SCORE <1% and CRP >3 mg/L at diagnosis plus syndesmophytes and carotid plaques or TC-SCORE <1% and CRP >3 mg/L at diagnosis plus extraarticular manifestations plus carotid plaques yielded the highest sensitivity (93.0%) for high/very high CV risk in these patients. The presence of syndesmophytes was associated with increased risk of carotid plaques in AS that fulfilled definitions for low CV risk according to the TC-SCORE (OR 8.75 [95% CI 2.11-36.40]; p=0.002). CONCLUSIONS: Our results support the use of carotid US in the assessment of CV risk in patients with AS.

Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis.

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.

Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis.

Osteoprotegerin (OPG), receptor activator of nuclear factor-ΚB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change = 1.79, p = 0.013 and 2.07, p = 0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change = 0.50, p = 0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change = 1.46, p = 0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p = 0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL.

Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy.

Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy.

The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet's disease: results of a multicentre open-label study.

OBJECTIVES: To assess the efficacy of other biologic therapies, different from infliximab (IFX) and adalimumab (ADA), in patients with Behçet's disease uveitis (BU). METHODS: Multicenter study of 124 patients with BU refractory to at least one standard immunosuppressive agent that required IFX or ADA therapy. Patients who had to be switched to another biologic agent due to inefficacy or intolerance to IFX or ADA or patient's decision were assessed. The main outcome measures were the degree of anterior and posterior chamber inflammation and macular thickness. RESULTS: Seven (5.6%) of 124 cases (4 women/3 men; mean age, 43 (range 28- 67) years; 12 affected eyes) were studied. Five of them had been initially treated with ADA and 2 with IFX. The other biologic agents used were golimumab (n=4), tocilizumab (n=2) and rituximab (n=1). The ocular pattern was panuveitis (n=4) or posterior uveitis (n=3). Uveitis was bilateral in 5 patients (71.4%). At baseline, anterior chamber and vitreous inflammation were present in 6 (50%) and 7 (58.3%) of the eyes. All the patients (12 eyes) had macular thickening (OCT>250µm) and 4 of them (7 eyes), cystoid macular edema (OCT>300 µm). Besides reduction anterior chamber and vitreous inflammation, we observed a reduction of OCT values, from 330.4±58.5 µm at the onset of the biological agent to 273±50 µm at month 12 (p=0.06). Six patients achieved a complete remission of uveitis. CONCLUSIONS: The vast majority of patients with BU refractory to standard immunosuppressive drugs are successfully controlled with ADA and/or IFX. Other biologic agents appear to be also useful.

Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review.

OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) in patients with Takayasu arteritis (TA). METHODS: Multicentre open-label retrospective study. RESULTS: Eight patients (all women) with a mean age of 34±16 years, median 36 years (range: 7-57) were assessed. The main clinical features at TCZ therapy onset were: constitutional symptoms (n=4), fever (n=3), headache (n=2), chest pain (n=1), abdominal pain (n=1), mesenteric ischaemia (n=1), myalgia involving the lower limbs (n=1), cerebral vascular insufficiency (n=1), malaise (n=1), upper limb claudication (n=1) and nodular scleritis (n=1). Besides corticosteroids and before TCZ treatment onset, 7 of 8 patients had also received several conventional immunosuppressive and/or biologic agents. Seven patients experienced marked clinical improvement in the first 3 months after the onset of TCZ therapy. After a median follow-up of 15.5 [interquartile range-IQR: 12-24] months, 7 patients were asymptomatic. The median C-reactive protein decreased from 3.09 [IQR: 0.5-12] to 0.15 [IQR: 0.1-0.5] mg/dL (p=0.018), and median erythrocyte sedimentation rate from 40 [IQ range: 28-72] to 3 [IQR: 2-5] mm/1st hour (p=0.012). The median dose of prednisone was also tapered from 42.5 [IQR: 25-50] to 2.5 [IQR: 0-7.5] mg/day (p=0.011). However, TCZ had to be discontinued in 1 patient because she developed a systemic lupus erythematosus, and in another patient due to inefficiency. TCZ dose was reduced in a patient because of mild thrombocytopenia. CONCLUSIONS: TCZ appears to be effective in the management of patients with TA, in particular in patients refractory to corticosteroids and/or conventional immunosuppressive drugs.

Anti-tumor necrosis factor-alpha therapy improves endothelial function and arterial stiffness in patients with moderate to severe psoriasis: A 6-month prospective study.

The aim of the present study was to determine if the use of the anti-tumor necrosis factor (TNF)-α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m2 or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow-mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty-nine patients were studied. Anti-TNF-α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti-TNF-α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.