Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME.
Retrospective case series.
Patients with CME secondary ...to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 μm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed.
A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 μm; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months.
Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.
Abstract Objective To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. Methods A ...retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8 mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. Results The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica ( n = 16), asthenia ( n = 7), headache ( n =5), constitutional symptoms ( n = 4), jaw claudication ( n = 2), and visual loss ( n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6–19) months, the C-reactive protein level had fallen from 1.9 (1.2–5.4) to 0.2 (0.1–0.9) mg/dL ( p < 0.0001) and the erythrocyte sedimentation rate decreased from 44 (20–81) to 12 (2–20) mm/1st hour ( p = 0.001). The median dose of prednisone was also tapered from 18.75 (10–45) to 5 (2.5–10) mg/day ( p < 0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis. Conclusion TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.
Leptin is an adipokine that participates in the regulation of the immune and inflammatory response. Chronic systemic inflammation contributes to the development of cardiovascular (CV) disease in ...rheumatoid arthritis (RA). In this study, we aimed to assess the short-term effect of the anti-IL-6 receptor tocilizumab (TCZ) administration on circulating leptin concentrations in patients with RA, as well as the potential association of leptin with CV risk factors and demographic and clinical characteristics of these patients.
We recruited 50 consecutive non-diabetic patients with RA undergoing periodic treatment with TCZ. Leptin serum levels were determined by a commercial immunoassay kit in samples obtained immediately prior to (pre-infusion) and 60 minutes after the end of a TCZ intravenous infusion (post-infusion).
A significant reduction of leptin levels was observed following the TCZ infusion (9.24±7.98 ng/mL vs. 7.92±7.32 ng/mL, pre- and post-infusion, respectively, p=0.002). Additionally, there was a strong positive correlation between body mass index of RA patients and basal levels of leptin (r=0.56; p=0.0001). Moreover, high basal levels of leptin in RA patients were associated with female sex (p=0.006), obesity (p<0.001) and rheumatoid factor negative status (p=0.006).
Our study disclosed a short-term effect of anti-IL-6 therapy on leptin serum levels in RA patients. Decreased leptin levels may explain the beneficial effect of anti-IL-6 blockade on CV disease associated to RA.
Abstract
Objectives
To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up.
...Methods
This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model.
Results
Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE 7.39 cases per 1000 person-years (95% CI 4.63, 11.18) was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years hazard ratio 4.60 (P =0.02), compared with those without CIRD.
Conclusions
Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.
Non-infectious aortitis is often refractory to standard immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of aortitis, we assessed the efficacy of the anti-IL6 receptor ...monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis.
Review of 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ.
The mean age±SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (n=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean±SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia.
TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs.
To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).
This is a ...cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.
888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.
Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.
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To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA).
Cross-sectional study of the Spanish AtheSpAin ...cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected.
611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values (p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027).
Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.
This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE.
RELESSER (Spanish Society of Rheumatology Lupus Registry) is a ...nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity.
Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex odds ratio (95% CI), 1.72 (1.07, 2.72), RP 1.63 (1.29, 2.05), interstitial lung disease 3.35 (1.84, 6.01), Jaccoud arthropathy 1.92 (1.40, 2.63), anti-Ro/SSA and/or anti-La/SSB autoantibodies 2.03 (1.55, 2.67), anti-RNP antibodies 1.48 (1.16, 1.90), MTX 1.67 (1.26, 2.18) and antimalarial drugs 0.50 (0.38, 0.67).
Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.
Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of ...the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk. Keywords: rheumatoid arthritis, lipoproteins, tumor necrosis factor inhibitors
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