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Fibromyalgia (FM) was frequently observed in patients with rheumatoid arthritis (RA). We aimed to evaluate the differences in psychiatric comorbidities and life adversities between patients with Rheumatoid arthritis + FM (secondary fibromyalgia [SFM]) and people with primary FM (PFM). In a cross‐sectional, observational study, patients with PFM and SFM underwent a structured interview for the lifetime diagnosis of major depression (MDD), panic disorder (PD) and post‐traumatic stress disorder (PTSD) and were assessed for childhood/adulthood adversities and FM‐related symptoms severity. Thirty patients with PFM and 40 with SFM were recruited. The univariate analysis showed that the lifetime rates of MDD were significantly higher in PFM versus SFM (76.7 % and 40%, respectively, p < 0.003), as well as the rates of PD (50 % and 15%, respectively, p < 0.003), whereas there was no difference in PTSD rates. The rates of sexual abuse and physical neglect were significantly higher in PFM patients versus SFM patients (p < 0.005 and p < 0.023). Life events occurring before FM onset were different in PFM and SFM groups. In the logistic regression model, lifetime PD and physical neglect remain independent risk factors for PFM. PFM and SFM differ in psychiatric comorbidities and environmental adversities, suggesting that common pathogenesis may develop through different pathways. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is the most severe extra‐articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10–20% of all RA mortality, no controlled studies are available for the treatment of RA‐ILD and its therapeutic approach is still debated. Aims: To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). Methods: In this national multicentre study, we retrospectively collected patients with RA‐ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high‐resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Results: Twenty‐eight RA‐ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non‐specific interstitial pneumonia pattern. Conclusions: The management of RA‐ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA‐ILD and a potential effect on the stabilisation of lung involvement. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERV)‐E consist of a family of more than 1300 elements, stably integrated in the human genome. Some of them are full‐length proviruses able to synthesize the viral proteins gag, pol and env. The reactivation of HERV‐E elements has been associated to placentation, cancer and autoimmunity. In this narrative review, we aimed to report the status of the art concerning the involvement of HERV‐E in rheumatic autoimmune diseases. Following a research on PubMed database, a total of 87 articles were selected. The highest amount of evidence derives from studies on systemic lupus erythematosus (SLE), whereas a few to no data are available on other immune‐mediated diseases. In SLE, the hyper‐expression of HERV‐E clone 4‐1 in peripheral blood mononuclear cells or differentiated lymphocytes has been associated with disease activity and autoantibody production. It is likely that HERV‐E take part to the pathogenesis of rheumatic autoimmune diseases but additional research is needed. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the 2‐year retention rate of golimumab compared with etanercept and adalimumab as second‐line biologic agent in rheumatoid arthritis (RA) patients who failed a previous tumor necrosis factor inhibitor (TNFi). Methods: Data on RA patients treated with a second‐line subcutaneous TNFi were extracted from a multicentric Italian cohort (the LORHEN registry). The analysis was limited to etanercept, adalimumab and golimumab in the period when all were available in Italy (since October 2010). The 2‐year retention rate was calculated by Kaplan–Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log‐rank test. Results: One hundred and ninety‐five RA patients treated with etanercept (n = 76), adalimumab (n = 68) or golimumab (n = 51) were included in the analysis. The 2‐year retention rate (40% with a median time‐on‐drug of 12.9 months in the whole population) was significantly lower for adalimumab (31.2%, P = 0.018) and numerically lower for etanercept (39.8%, P = 0.068) compared with golimumab (53.4%) because of a higher discontinuation rate due to adverse events (P = 0.042 and P = 0.038 versus golimumab, respectively). Drug survival was greater in concomitant synthetic disease modifying anti‐rheumatic drug (sDMARD) users (44.2%) compared with TNFi monotherapy (22.5%, P = 0.036). No difference was found in survival analysis according to first‐line TNFi reason for discontinuation and pattern of TNFi switch (antibody‐receptor, antibody‐antibody or receptor‐antibody). Conclusions: Our real‐life data confirmed switching to a second TNFi as a good option for treating first‐line TNFi failures in RA, especially in combination with sDMARDs. Second‐line golimumab showed an overall better 2‐year drug survival compared with adalimumab and etanercept. [ABSTRACT FROM AUTHOR]

Objective To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia ( FM), and to delineate the characteristics of these patients. Methods Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis ( BSRBR- AS). All patients are required to meet Assessment of SpondyloArthritis international Society ( ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. Results Of the patients registered in the BSRBR- AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. Conclusion Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between smoking, smoking cessation, and disease characteristics and quality of life (QoL) in spondyloarthritis.Methods: The Scotland Registry for Ankylosing Spondylitis collects data from clinically diagnosed patients with spondyloarthritis. Clinical data, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) scores, were obtained from medical records. Mailed questionnaires contained information on smoking status and QoL (Ankylosing Spondylitis QoL questionnaire [ASQoL]). Linear and logistic regression were used to quantify the effect of smoking, and smoking cessation, on various disease-specific and QoL outcomes, with adjustments for age, sex, deprivation, education level, and alcohol use. Results are presented as regression coefficients (β) or odds ratios (ORs) with 95% confidence intervals (95% CIs).Results: Data were obtained from 946 participants (73.5% male, mean age 52 years). Current smoking was reported by 22%, and 38% were ex-smokers. Ever smokers had poorer BASDAI (β = 0.5 [95% CI 0.2, 0.9]) and BASFI scores (β = 0.8 [95% CI 0.4, 1.2]), and reported worse QoL (ASQoL β = 1.5 [95% CI 0.7, 2.3]). Compared to current smokers, ex-smokers reported less disease activity (BASDAI β = -0.5 [95% CI -1.0, -0.04]) and significantly better QoL (ASQoL β = -1.2 [95% CI -2.3, -0.2]). They also were more likely to have a history of uveitis (OR 2.4 [95% CI 1.5, 3.8]).Conclusion: Smokers with spondyloarthritis experience worse disease than those who are never smokers. However, this study provides new evidence that, among smokers, smoking cessation is associated with lower disease activity and better physical function and QoL. Clinicians should specifically promote smoking cessation as an adjunct to usual therapy in patients with spondyloarthritis. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting.Methods: Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months.Results: In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection.Conclusion: Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Objective The American College of Rheumatology (ACR) 1990 fibromyalgia classification criteria are based on the presence of widespread pain and tenderness. In 2010, new criteria were proposed that focused more on multiple symptoms, and these criteria were later modified to require only self report of symptoms. The current study aimed to determine the population prevalence of fibromyalgia and to compare differences in prevalence using the alternative criteria. Methods A cross-sectional survey was conducted. Questionnaires, including items on pain, symptoms, and rheumatologic diagnoses, were mailed to 4,600 adults in northeast Scotland. Participants who had chronic widespread pain or those who met the modified 2010 criteria, plus a subsample of other participants, were invited to attend a research clinic. Attendees completed an additional questionnaire and underwent a rheumatologic examination, and their signs and symptoms were classified according to the ACR 1990, 2010, and modified 2010 criteria. The prevalence of fibromyalgia according to each set of criteria was calculated, weighting back to the target population by age, sex, and area of residence. Results Of 1,604 questionnaire participants, 269 were invited to attend the research clinic, and 104 (39%) attended; 32 of these subjects (31%) met ≥1 set of fibromyalgia criteria. The prevalence of fibromyalgia according to the 1990, 2010, and modified 2010 criteria was 1.7% (95% confidence interval [95% CI] 0.7-2.8), 1.2% (95% CI 0.3-2.1), and 5.4% (95% CI 4.7-6.1), respectively. The ratio of females to males was 13.7:1, 4.8:1, and 2.3:1 of those meeting the respective criteria sets. Conclusion Fibromyalgia prevalence varies with the different sets of classification criteria applied. In particular, prevalence is higher and a greater proportion of men are identified with the modified 2010 criteria as compared to the criteria sets requiring clinician input. This has important implications for the use of the new criteria, both in research and in clinical practice. [ABSTRACT FROM AUTHOR]

Objective An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients. Methods The study involved 20 patients (2 men and 18 women with a mean ± SD age of 52.96 ± 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age- and sex-matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels. Results All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (β) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower ( P = 0.0033) and plasma ADMA levels were higher ( P < 0.0001) than in healthy controls. Conclusion SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement. [ABSTRACT FROM AUTHOR]

Objective Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti-tumor necrosis factor α (anti-TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs. Methods Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as <25, 25-30, and >30 kg/m2), acute-phase reactants, IgM rheumatoid factor, and anti-cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of <2.6 lasting for at least 3 months. Results Six hundred forty-one outpatients with longstanding RA receiving anti-TNFα blockers (adalimumab, n = 260; etanercept, n = 227; infliximab, n = 154), recruited from 2006-2009 and monitored for at least 12 months, were analyzed. The mean ± SD DAS28 at baseline was 5.6 ± 1.4. A BMI of >30 kg/m2 was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti-TNFα treatment, a DAS28 of <2.6 was noted in 15.2% of the obese subjects, in 30.4% of the patients with a BMI of 25-30 kg/m2, and in 32.9% of the patients with a BMI of <25 kg/m2 ( P = 0.01). The lowest percentage of remission, which was statistically significant versus adalimumab and etanercept ( P = 0.003), was observed with infliximab. Conclusion Obesity represents a risk factor for a poor remission rate in patients with longstanding RA treated with anti-TNFα agents. A personalized treatment plan might be a possible solution. [ABSTRACT FROM AUTHOR]

Objective To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). Methods The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). Results The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti-cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti-tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77-117.39], P = 0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7-152.5], P = 0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2-7.8], P = 0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. Conclusion BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, sleep alterations, and distress. Emerging evidence points toward augmented pain processing within the central nervous system as having a primary role in the pathophysiology of this disorder. Recent studies have identified distinct FM subgroups on the basis of clinical, neurochemical, and neuroendocrinological abnormalities, including increased cerebrospinal fluid levels of substance P and excitatory amino acids and functional abnormalities in the hypothalamic–pituitary–adrenal axis, and sympathoadrenal (autonomic nervous) system. Pharmacological treatments have been gradually enriched by a variety of compounds. Antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, and alpha2-delta agonists have all been used to treat FM with varying results. Physical exercise and multimodal cognitive-behavioral therapy seem to be the most widely accepted and beneficial forms of nonpharmacological therapy. Studies predicting treatment response indicate that it is useful if not essential to tailor the choice of treatment components to the needs of individual patients. [ABSTRACT FROM AUTHOR]

Immunological, epidemiological, and clinical evidence suggest that female sex hormones play an important role in the etiology and pathophysiology of chronic immune/inflammatory diseases. Several significant factors generate confusion and opposite conclusions in evaluating the role of estrogens in these diseases, including relatively superficial translational studies from animals to the human condition, the different effects of estrogens on their different receptors or on different target cells, the different estrogen concentrations employed, and opposite effects (especially on cell proliferation) exerted by different peripheral estrogen metabolites. A preponderance of 16α-hydroxylated estrogens, as observed in rheumatoid arthritis synovial fluids, is an unfavorable sign in synovial inflammation. Since 17β-estradiol administered during hormone replacement therapy will rapidly increase estrone sulfate after conversion in adipose tissue by aromatases, hormone replacement therapy can have proinflammatory effects by providing estrone sulfate to the inflamed synovial tissue. In addition, it appears that the use of combined oral contraceptives is associated with an increased risk of at least systemic lupus erythematosus. In conclusion, estrogens are generally considered as enhancers of cell proliferation and humoral immune response. [ABSTRACT FROM AUTHOR]

A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology Network (LOHREN) registry and receiving anti-TNF therapy was evaluated after 6, 12, 24, and 36 months. Of the 1114 patients in the registry 1064 met the clinical criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242 etanercept. The therapeutic survival curve of these patients showed that the likelihood of continuing anti-TNF therapy was 78.8% after 12 months, 65.2% after 24 months, and 52.9% after 36 months, with a risk of dropout similar for inefficacy and adverse events. There were 405 anti-TNF therapy discontinuations (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%) other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart failure) were considered to be related to anti-TNF therapy. Of the discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the likelihood of survival on etanercept (62.5%) was significantly greater than the likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk of therapy discontinuations due to adverse events was associated with increasing age, a corticosteroid >5 mg/day, a high erythrocyte sedimentation rate (ESR), a higher risk of therapy discontinuations due to inefficacy was associated with the previous use of ≥4 disease-modifying antirheumatic drugs (DMARDs) and a high ESR. Comorbidities, increasing DAS28 values and co-therapy with methotrexate were associated with a lower risk of discontinuation. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil (MMF) is an immunosuppressive agent initially used in the treatment of transplant recipients. MMF has been used in renal, heart, and liver transplantation, where it seems more effective than other immunosuppressive regimens in reducing the incidence of acute rejection episodes. MMF has a variety of immunosuppressive effects, including selective suppression of T and B lymphocyte proliferation, and has been more recently used in many autoimmune inflammatory conditions. Systemic lupus erythematosus (SLE) is an autoimmune disease that can potentially involve any organ or system of the human body. Glomerulonephritis (GLN) has been recognized as the most frequent severe manifestation of SLE, leading to poor long-term prognosis. In the treatment of lupus GLN, several therapeutic approaches, all including immunosuppressive drugs, such as cyclophosphamide, azathioprine, or cyclosporine A, have been used. The short- and long-term toxicity of these drugs limits their use in a substantial number of patients. Over the last few years, MMF has emerged as an alternative therapeutic regimen in lupus GLN, mainly for patients refractory to other therapies. These studies have shown that it is highly effective and generally well tolerated. [ABSTRACT FROM AUTHOR]

Systemic autoimmune diseases are characterized by the presence in patient sera of high titers of autoantibodies directed against self-antigens. The characterization of specific autoantigen–autoantibody system is very important for research as well as for diagnostic tools and several techniques can be employed in such immunological studies. In this review an overview of the different biochemical methods of antigen preparation and the specific methodological applications is given, also describing potential critical aspects and benefits of the different protocols. [ABSTRACT FROM AUTHOR]

Cardiovascular involvement in rheumatoid arthritis (RA) is common, although the true prevalence of cardiac abnormalities is difficult to measure, as much disease remains clinically silent. The pathogenesis of cardiac lesions in RA is related to the primary disorder of microcirculation with diffuse arteriolar and capillary lesions. Previous studies demonstrated that coronary flow reserve (CFR) is impaired in patients with connective tissue diseases (CTD). This review focuses on transthoracic Doppler echocardiography as a noninvasive method used to assess CFR in RA patients. CFR is early reduced in RA patients without clinical evidence of heart disease as a result of impaired microcirculation. CFR seems a useful technique able to follow-up and to assess effects of new drugs on RA patients. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu-like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic-pituitary-adrenal (HPA) axis, pain-processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) inhibitors are associated with greater improvements in the symptoms and signs of rheumatoid arthritis (RA) and, more importantly, a lower risk of joint damage. TNF is an important mediator of the alterations in neuroendocrine axes characterizing RA. Long-term therapy with anti-TNF agents sensitizes the pituitary gland and improves adrenal androgen secretion, thus stimulating an alternative form of anti-inflammatory action. [ABSTRACT FROM AUTHOR]

In a chronic inflammatory disease, such as rheumatoid arthritis (RA), the hypothalamic-pituitary-adrenal axis is altered in three ways: (1) the inflammation-related spontaneous and stimulated secretion of cortisol is inadequate; (2) the inflammation-related secretion of adrenocorticotropic hormone (ACTH) is low; and (3) the levels of adrenal androgens decrease. In patients with RA, long-term therapy with anti-TNF therapy sensitizes the pituitary gland and improves adrenal androgen secretion. We have recently found that the mean serum levels of ACTH, cortisol, 17-hydroxyprogesterone (17OHP), and androstenedione (ASD) in 11 prednisolone-naïve patients with psoriatic arthritis did not markedly change during 12 weeks of etanercept treatment, nor did the serum cortisol/ACTH ratio. However, the greater increase in serum cortisol in comparison with serum 17OHP or ASD was related to clinical improvement, which indicates that the improvement was more related to the higher cortisol levels. [ABSTRACT FROM AUTHOR]

Objective: Some patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) improve rapidly from anti-tumor necrosis factor (anti-TNF) therapy. No sensitive markers are available that might predict outcome of anti-TNF therapy. We undertook this study to investigate the predictive value of hypothalamic-pituitary-adrenal (HPA) axis hormones for clinical improvement during anti-TNF therapy., Methods: An observational study in 23 RA patients was followed by a validation study in 38 RA patients. The patients receiving anti-TNF antibodies had no glucocorticoid treatment, and we measured baseline serum levels of adrenocorticotropic hormone (ACTH) and cortisol. Improvement during anti-TNF antibody treatment was judged by the Disease Activity Score in 28 joints (DAS28), and serum levels of cortisol were measured at followup., Results: The observational study demonstrated that improvement in the DAS28 correlated negatively with baseline serum levels of cortisol (R=-0.520, P=0.011) and the cortisol:ACTH ratio (R=-0.700, P=0.0002). In the longitudinal part of the study at followup, those patients with good improvement and initially low serum levels of cortisol demonstrated an increase of serum cortisol, in contrast to patients with little or no improvement. Findings in the observational study were supported by those in the validation study in a group of RA patients with less inflammation (correlation of improvement in the DAS28 with cortisol:ACTH ratio: R=-0.320, P=0.025)., Conclusion: This is the first study in a human chronic inflammatory disease to demonstrate that inflammation-induced TNF interferes with HPA axis integrity, which is linked to the disease outcome. These findings position the HPA axis centrally in the vicious circle of perpetuation of chronic inflammation.