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-? 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

ABSTRACT: 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 commentary: 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 openlabel 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, anti-tumor necrosis factor- α therapy yielded disappointing results in GCA

Adipokines, Biomarkers of Endothelial Activation, and Metabolic Syndrome in Patients with Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS

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 highCVrisk.None of them was found to have a high/very high TC-SCORE. CRP > 3mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, \u1d45d� = 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 hadCRP> 3mg/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

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. Anti-tumor 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

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients

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 6months of therapy, a negative correlation between TBS and insulin resistance (?? = 0.02) and leptin (?? = 0.01) and a positive correlationwith adiponectin were found (?? = 0.01).The best set of predictors for TBS values at baseline were female sex (?? = 0.015), age (?? = 0.05), and BMI (?? = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (?? = 0.001), BMI (?? < 0.0001), and serumadiponectin levels (?? = 0.027). In conclusion, in nondiabetic patients withmoderate-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

Lack of Association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and Carotid Intima-Media Thickness, Carotid Plaques, and Cardiovascular Disease in Patients with Rheumatoid Arthritis

Introduction. Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.European Union FEDER Funds and “Fondo de Investigación Sanitaria” (Grants PI06/0024, PS09/00748, and PI12/00060) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009/0013 and RD12/0009/0004 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain) and in part by grants from the European IMI BTCure Program.Peer reviewe

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome

Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory