The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA.
Recommendations were ...established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists.
Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases.
The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.
Objectives To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic arthritis, and ...macular edema. Methods Systematic review. We conducted a sensitive literature search in Medline (from 1961) and EMBASE (from 1980) until October 2007. Selection criteria were as follows: (1) population: autoimmune posterior uveitis, chronic anterior uveitis in juvenile idiopathic arthritis, and macular edema; (2) intervention: immunosuppressive and biologic therapies; (3) outcomes: visual acuity, Tyndall, vitreous haze, macular edema, pars planitis, and retinal vasculitis. There were no limitations regarding study design. The quality of each study was evaluated using the Jadad's scale and Oxford Levels of Evidence. Results Two hundred sixty-five articles were selected for detailed review of the 4235 found in the initial search: 128 records were on immunosuppressants, 105 on biological therapies, and 32 on macular edema. Overall, both the immunosuppressive and the biologic therapies appeared effective in the treatment of autoimmune posterior uveitis, except for daclizumab in uveitis related to Behçet's disease, and for etanercept in any uveitis. In the treatment of macular edema, the drugs tested were also effective. Conclusions Based on the evidence collated, immunosuppressants and biological therapies (except for daclizumab in Behçet and etanercept) may be effective in autoimmune uveitis and macular edema. No superiority may be inferred from this review.
Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal ...influenza vaccine.
Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied.
253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054).
Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.
The aim of the study was to analyze the efficacy and satisfaction of multidisciplinary dermatology–rheumatology management for patients with moderate-to-severe psoriasis and psoriatic arthritis ...(PsA). We conducted a systematic literature search in MEDLINE, EMBASE, and Cochrane Library up to September 2015. Selection criteria include (1) adult patients with moderate-to-severe psoriasis and PsA, (2) assessed in a multidisciplinary consultation, (3) comparison with routine separate consultations, and (4) outcome measures to evaluate efficacy and/or satisfaction. Meta-analyses, systematic reviews, clinical trials, cohort studies, and case series were included. The quality of the studies included was graded according to the Oxford Level of Evidence scale. Of 195 articles, three studies complied with the inclusion criteria: two case series and one descriptive study in which 506 patients were evaluated. Patients were referred to the multidisciplinary consultation from dermatology and rheumatology consultations in all but one study, in which primary care was also involved. The reason for the referral was to confirm the diagnosis and/or treatment. Patients were evaluated on a weekly and monthly basis in two and one study, respectively. The evidence obtained is scarce but suggests the efficacy of multidisciplinary consultations in terms of improved skin and joint symptoms after changing treatment (82–56 %), showing higher scores for this type of consultation compared to the usual 4.91 vs. 2.85 (0–5) and a high level of satisfaction among patients (94 % “very satisfied”). However, waiting times were higher. With the limited evidence found, multidisciplinary management seems to be more effective and more satisfactory for patients with moderate-to-severe psoriasis and PsA than conventional consultations, though this could not be conclusively demonstrated. The results of this review support the benefit of implementing this type of consultation.
Data on infections in patients exposed to biologic therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other immune-mediated connective tissue ...diseases (ICTD). The purpose of this study was to describe and to compare the risk of serious infections (SI) in patients with RA and other ICTD on anti-TNF or rituximab and to identify predictors of SI. We analyzed RA or other ICTD patients on anti-TNF or rituximab included in the Spanish registry BIOBADASER 2.0 (2000–2011). For each disease group, incidence rate (IR), mortality rate (MR) and IR ratio (IRR) of SI with 95 % CI were estimated. Risks were then standardized by age and sex to the general population. Risk factors for SI were assessed by Poisson regression models. A total of 3,301 patients on anti-TNF (
n
= 3,166) or rituximab (
n
= 135), of which 176 (5 %) had ICTD other than RA, were analyzed. IR of SI was higher in non-RA ICTD than in RA, with an IRR of 3.15 (95 % CI 1.86, 5.31) before adjustment and 1.96 (95 % CI 1.06, 3.65) after adjustment for age, comorbidity and corticoid use. Mortality due to infections was higher in ICTD although it did not reach statistical significance. Age, disease duration, comorbidities, corticosteroids and ICTD different to RA were all independently associated with SI. Patients with ICTD other than RA are at a high risk of SI when prescribed anti-TNF or rituximab, partly due to the excess comorbidity and immunosuppressive co-treatment, but also to the inflammatory disease. When evaluating the risk/benefit ratio of off-label medications in ICTD patients, age, comorbidities and corticoid use should carefully be taken into account, applying adequate preventive measures.
KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of ...the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status.
All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival.
The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01–2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06–1.91).
KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.
To generate recommendations on the use of immunomodulators in patients with non-infectious, non-neoplastic intermediate uveitis (IU), posterior uveitis (PU) and panuveitis (PanU) based on best ...evidence and experience.
A multidisciplinary panel of 5 experts was established, who defined the scope, users, and sections of the document. A systematic literature review (SLR) was performed to assess the efficacy and safety of immunomodulatory drugs in patients with non-infectious, non-neoplastic, non-anterior uveitis. The results of the SLR were presented and discussed during an expert meeting in which 34 recommendations were generated. The level of agreement with the recommendations was also tested in 25 additional experts following a Delphi process. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of the experts voted ≥7. The level of evidence and grade or recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence.
The SLR included 33 articles. The 34 recommendations were accepted after 2 Delphi rounds (3 of them were modified after the first round). They include specific recommendations on patients with non-infectious, non-neoplastic, PU and PanU, as well as different treatment guidelines.
In patients with non-infectious, non-neoplastic, non-anterior uveitis these recommendations might help treatment decision making, due to the lack of robust evidence or other globally accepted algorithms.
Purpose
To compare the clinical prognosis among selected white dot syndromes (WDS) (birdshot chorioretinopathy (BRC), multifocal choroiditis, serpiginous choroidopathy (SC), and others) and to ...identify risk factors of poor visual prognosis.
Methods
Retrospective longitudinal cohort study including 84 patients (143 affected eyes) diagnosed with WDS between 1982 and July 2017, followed up until loss of follow-up or December 2017, and recruited from three Uveitis Clinics (Madrid Community, Spain). Our main outcome measures were temporary or permanent moderate (corrected visual acuity in the Snellen scale < 20/50) or severe (< 20/200) vision losses, and development of new ocular complications. Incidence rates (IR) of the main outcome measures were estimated per 100 eye-years. Bivariate and multivariate Cox robust regression models analyzed the association of demographic- and clinical-related variables with vision loss.
Results
SC exhibited the greatest IR of vision loss, even in the multivariate models. Previous events of vision loss, presence of choroidal neovascularization, and cataracts exhibited worse visual prognosis. Monotherapy with immunosuppressive drugs but not combine therapy was also associated with higher IR of visual loss. Regarding new ocular complications, BRC showed the highest IR of epiretinal membrane and macular edema.
Conclusions
SC presents the worst visual prognosis. Some ocular manifestations can identify patients with WDS at risk of a worse clinical evolution.
Low-cardiac output syndrome (LCOS) after cardiac surgery secondary to systemic hypoperfusion is associated with a higher incidence of renal and neurological damage. A range of effective therapies are ...available for LCOS. The beneficial systemic effects of levosimendan persist even after cardiac output is restored, which suggests an independent cardioprotective effect.
A double-blind clinical trial was conducted in patients with a confirmed diagnosis of LCOS randomized into two treatment groups (levosimendan
dobutamine). Monitoring of hemodynamic (cardiac index, systolic volume index, heart rate, mean arterial pressure, central venous pressure, central venous saturation); biochemical (e.g. creatinine, S100B protein, NT-proBNP, troponin I); and renal parameters was performed using acute kidney injury scale (AKI scale) and renal and brain ultrasound measurements vascular resistance index (VRI) at diagnosis and during the first 48 h.
Significant differences were observed between groups in terms of cardiac index, systolic volume index, NT-proBNP, and kidney injury stage at diagnosis. In the levosimendan group, there were significant variations in AKI stage after 24 and 48 h. No significant differences were observed in the other parameters studied.
Levosimendan showed a beneficial effect on renal function in LCOS patients after cardiac surgery that was independent from cardiac output and vascular tone. This effect is probably achieved by pharmacological postconditioning.
EUDRA CT, identifier 2014-001461-27. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001461-27.
To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU).
Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase ...(1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009).
We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses.
Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.
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