Open-Label Observation of Addition of Etanercept Versus a Conventional Disease-Modifying Antirheumatic Drug in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy in the Latin American Region

Machado, Daniel Aragão; Guzmán, Renato; Xavier, Ricardo Machado; Simón, J. Abraham; Mele, Linda; Pedersen, Ronald; Ferdousi, Tahmina; Koenig, Andrew; Kotak, Sameer; Vlahos, Bonnie

doi:10.1097/rhu.0000000000000055

Cited by 39 publications

(49 citation statements)

References 22 publications

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“…Similar findings were published by Machado et al using a study design similar to the previous, highlighting a significant improvement in depression [116]. Contrary findings were published by Pinho de Oliveira Ribeiro et al which concluded that patients treated with biologic drugs had the highest average scores for the signs and symptoms of anxiety, depression, and suicidal ideation, contrary to patients treated with methotrexate and leflunomide who had the lowest averages for all categories.…”

Section: Depression and Rheumatoid Arthritiscontrasting

confidence: 50%

The inflammatory perspective of depression in the context of chronic medical conditions

Azevedo-Pinto¹,

Santos²,

Doellinger³

et al. 2016

IJCNMH

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Background: The inflammatory hypothesis of depression implies that an unbalance of the immune system may trigger abnormal responses, affecting neural signalling mediators and the hypothalamic-pituitary-adrenal axis. This theory underlies a bidirectional hypothesis on the influence of depressive symptoms in the clinical course of chronic inflammatory disorders (CID), as well as in the genesis of mood disturbances. We aim to review current knowledge on depressive disorders and chronic inflammatory diseases as comorbidities and the underlying pathophysiologic mechanisms.

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Section: Depression and Rheumatoid Arthritiscontrasting

confidence: 50%

The inflammatory perspective of depression in the context of chronic medical conditions

Azevedo-Pinto¹,

Santos²,

Doellinger³

et al. 2016

IJCNMH

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“…In spite of this, only 1 bias factor contributed to heterogeneity and had a statistically significant impact on the outcomes. This bias involved 2 studies, which were performed in Asia and Latin America, in patients with long disease duration, an inadequate response to previous DMARDs, and no treatment with a course of GC (11,12,16). In contrast, the other studies (3,4,9,10,13,15) were performed in North America and Europe, and generally in DMARD-naive early arthritis patients.…”

Section: Discussionmentioning

confidence: 99%

“…Concerning outcomes, only 1 study presented ESRs (14), 1 study presented CRP levels (11), and 3 studies presented joint swelling scores (10,14,16). Consequently, these outcomes, which we defined in the protocol, were not summarized in the present analysis.…”

mentioning

confidence: 99%

“…All analyses showed heterogeneity at 6 months, but few at 12 and 24 months. At 6 months, heterogeneity disappeared after the elimination of studies or treatment arms not using GC (3,11,12,16), which resulted in nonsignificant differences between a TNF inhibitor plus methotrexate and combination DMARD treatment (Figures 4 and 5, and Supplementary Figures 1 and 2), with the exception of radiographic progression ( Figure 3) and ACR70 response, (Supplementary Figure 3).…”

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confidence: 99%

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Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Graudal

Hubeck-Graudal

Faurschou

et al. 2015

Arthritis Care & Research

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Objective. The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. Methods. Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. Results. The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (20.09 units [20.61, 0.44]) of treatment or during the first 2 years (0.66 units [20.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. Conclusion. The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.

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“…Meta-analysis of RCTs of adjunctive treatment with anti-cytokine therapy Of three trials [48][49][50] that used anti-cytokine drugs as adjunctive treatment, two provided enough data for meta-analysis (Figure 2b). 49,50 Both of these studies compared combination of etanercept and a DMARD (n = 544) with DMARD alone (n = 405).…”

Section: Resultsmentioning

confidence: 99%

Antidepressant activity of anti-cytokine treatment: A systematic review and meta- analysis of clinical trials of chronic inflammatory conditions

Kappelmann

Lewis

Dantzer

et al. 2017

Brain, Behavior, and Immunity

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Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD) = 0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD = 0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight nonrandomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD = 0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P = 0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.

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Open-Label Observation of Addition of Etanercept Versus a Conventional Disease-Modifying Antirheumatic Drug in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy in the Latin American Region

Cited by 39 publications

References 22 publications

The inflammatory perspective of depression in the context of chronic medical conditions

The inflammatory perspective of depression in the context of chronic medical conditions

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Antidepressant activity of anti-cytokine treatment: A systematic review and meta- analysis of clinical trials of chronic inflammatory conditions

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