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.
Interstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The ...absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable.
To review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management.
PUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators.
Nine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%–91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%–75%), and it was used as first-line biologic agent in 22.8%–64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%–92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4–47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified.
Current evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.
Abstract
Background
Previous studies have shown that risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the actual cardiovascular (CV) risk of ...patients with rheumatoid arthritis (RA). In contrast, carotid ultrasound was found to be useful to identify RA patients at high CV. In the present study, we aimed to determine if specific disease features influence the CV risk reclassification of RA patients assessed by SCORE risk charts and carotid ultrasound.
Methods
1279 RA patients without previous CV events, diabetes, or chronic kidney disease were studied. Disease characteristics including disease activity scores, CV comorbidity, SCORE calculation, and the presence of carotid plaque by carotid ultrasound were assessed. A multivariable regression analysis was performed to evaluate if the reclassification into very high CV risk category was independently associated with specific features of the disease including disease activity. Additionally, a prediction model for reclassification was constructed in RA patients.
Results
After carotid ultrasound assessments, 54% of the patients had carotid plaque and consequently fulfilled definition for very high CV risk. Disease activity was statistically significantly associated with reclassification after fully multivariable analysis. A predictive model containing the presence of dyslipidemia and hypertension, an age exceeding 54 years, and a DAS28-ESR score equal or higher than 2.6 yielded the highest discrimination for reclassification.
Conclusion
Reclassification into very high CV risk after carotid ultrasound assessment occurs in more than the half of patients with RA. This reclassification can be independently explained by the activity of the disease.
Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic ...symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD. Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.
Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this ...disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD−. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-κB and TGF-β1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD.
The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as ...well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.
Abstract
Objective
To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD).
Methods
Multicentre study of patients with BD-associated uveitis. Patients were ...refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects.
Results
We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively.
Conclusion
TCZ could be a therapeutic option in patients with BD and refractory uveitis.
Abstract
BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally,
BAFF, APRIL
and
BAFFR
polymorphisms were associated with immune-mediated ...conditions, being
BAFF
GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether
BAFF, APRIL
and
BAFFR
represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition.
BAFF
rs374039502, which colocalizes with
BAFF
GCTGT>A, and two tag variants within
APRIL
(rs11552708 and rs6608) and
BAFFR
(rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when
BAFF, APRIL
and
BAFFR
variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of
BAFF, APRIL
or
BAFFR
when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when
APRIL
and
BAFFR
haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that
BAFF, APRIL
and
BAFFR
do not contribute to the genetic network underlying IgAV.
Abstract
Objective
Because carotid plaques predict the development of cardiovascular events in RA, we aimed to assess if the combined use of the systematic coronary risk evaluation (SCORE) and the ...QRISK3 algorithms allows for the identification of RA patients with carotid plaques in a defined population-based RA inception cohort.
Methods
A set of consecutive RA patients without a history of diabetes, chronic kidney disease or cardiovascular events were studied by carotid US between 2012 and 2019. Modified SCORE (mSCORE) for RA based on the 2015/2016 updated EULAR recommendations and QRISK3 algorithms were retrospectively tested using baseline data obtained at the time of the carotid US assessment.
Results
A total of 466 (54%) of 865 patients had carotid plaques. Using dichotomized QRISK3 and EULAR mSCORE, 73.2% (95% CI: 68.4.8, 77.6) of patients with QRISK ≥ 10% and EULAR mSCORE < 5% had plaque. In this group, the diagnostic odds ratio was 5.79 (95% CI: 4.14, 8.10). However, if both algorithms were above their thresholds of high cardiovascular risk (QRISK ≥ 10% and EULAR mSCORE ≥ 5%), the sensitivity increased up to 83.3% (95% CI: 72.1, 91.4) and the diagnostic odds ratio up to 10.6 (95% CI: 5.13, 22.0). When the risk charts scales were used as continuous variables, both QRISK3 and EULAR mSCORE were found positively associated with plaque. For each 1% QRISK3 or EULAR mSCORE increase, the probability of having plaques multiplied by 1.14 and 1.22, respectively. However, the effects of both algorithms did not multiply by each other.
Conclusions
. The combined use of QRISK3 and EULAR mSCORE allows for the identification of most RA patients at high risk of carotid plaques.
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