Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial

Kekow, J; Moots, Robert J.; Emery, Paul; Durez, Patrick; Koenig, Andrew; Singh, Amitabh; Pedersen, Ronald; Robertson, Deborah; Freundlich, Bruce; Sato, Reiko

doi:10.1136/ard.2008.102509

Cited by 108 publications

(66 citation statements)

References 22 publications

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“…Numerous randomized clinical studies have found that significantly more patients achieve DAS28 decrease of ≥1.2 and remission when biologic treatment is received within 1 year of diagnosis compared with later [3,4,[22][23][24][25][26][27][28]. This study confirms that the same response is consistently observed in real-world clinical practice in three different countries in Europe.…”

Section: Discussionsupporting

confidence: 87%

A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization

et al. 2015

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This retrospective medical chart review aimed to provide a current, real-world overview of biologic usage in patients with rheumatoid arthritis (RA) in Germany, Spain, and the UK, and estimate clinical and healthcare utilization outcomes associated with early versus late treatment. Adults (≥18 years) with a confirmed RA diagnosis between January 2008 and December 2010, who received biologic treatment for ≥3 months and had ≥12 months of follow-up were included. Early treatment was receipt of biologic agent ≤1 year after RA diagnosis. Outcomes included 28-joint disease activity score (DAS28) reduction of ≥1.2 from biologic start and remission (DAS28 < 2.6). Time to outcome was evaluated using Kaplan-Meier curves and log-rank tests. Of 328 patients enrolled (Germany [n = 111], Spain [n = 106], UK [n = 111]), 58.2 % received early biologic (Germany: 55.0 %, UK: 55.9 %, Spain: 64.2 %; p = 0.321). First-line biologics were more frequent in Spain (26.4 %) and Germany (19.8 %) versus the UK (7.2 %; p < 0.001). Late-treated patients were hospitalized more often than early-treated patients (10.5 vs 2.9 % [p = 0.006] for 9.0 vs 5.4 mean inpatient days [p = 0.408]). DAS28 was 5.1 at biologic initiation (n = 310); 73.5 % of patients had a DAS28 decrease of ≥1.2 and 44.5 % achieved remission. More patients had DAS28 decrease of ≥1.2 (79.2 vs 65.9 %; p = 0.009) and remission (51.1 vs 35.6 %; p = 0.007) with early versus late treatment, with a significant difference in Kaplan-Meier curves when indexing on time since diagnosis (p < 0.001) and biologic start (p = 0.024). In RA patients receiving biologic therapy, over half received biologic therapy early. Early initiation was associated with improved clinical outcomes and reduced hospitalization rates versus late treatment.

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Section: Discussionsupporting

confidence: 87%

A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization

et al. 2015

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“…In this study, leflunomide was associated with the lowest scores of both anxiety and depression [113]. Similarly, Kekow et al reported no significant change in depression scores in patients with early active rheumatoid arthritis treated with etanercept+MTX compared with those treated with MTX only [117]. Despite underlining the importance of future studies in this area, these differences may result from different study designs, as well as different populations and stages/severity of disease.…”

Section: Depression and Rheumatoid Arthritismentioning

confidence: 38%

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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“…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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Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial

Cited by 108 publications

References 22 publications

A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization

A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization

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

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

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