Leflunomide in monotherapy of rheumatoid arthritis: meta‑analysis of randomized trials

Golicki, Dominik; Newada, Maciej; Lis, J; Pol, Kaja; Hermanowski, Tomasz; Tłustochowicz, Małgorzata

doi:10.20452/pamw.1131

Cited by 31 publications

(18 citation statements)

References 35 publications

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“…Reasoning that these neural crest programmes are important in melanoma growth, we designed a screen using a library of ~2,000 chemicals in zebrafish embryos to find suppressors of the crestin + lineage using in situ hybridization. We found that inhibitors of the metabolic enzyme dihydroorotate dehydrogenase (DHODH), such as leflunomide, which is used for patients with rheumatoid arthritis 64 , completely suppressed the expression of crestin and downstream genes such as sox10 and mitfa . Leflunomide primarily acts at the level of the neural crest stem cell and does not act on differentiated derivatives, and inhibition of DHODH was shown to interfere with the transcriptional elongation of key genes that are required for neural crest development (such as mitfa ), as well as Myc-target genes that are known to be required for neural crest development 65 .…”

Section: Zebrafish As a Cancer Modelmentioning

confidence: 99%

Zebrafish cancer: the state of the art and the path forward

2013

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The zebrafish is a recent addition to animal models of human cancer, and studies using this model are rapidly contributing major insights. Zebrafish develop cancer spontaneously, after mutagen exposure and through transgenesis. The tumours resemble human cancers at the histological, gene expression and genomic levels. The ability to carry out in vivo imaging, chemical and genetic screens, and high-throughput transgenesis offers a unique opportunity to functionally characterize the cancer genome. Moreover, increasingly sophisticated modelling of combinations of genetic and epigenetic alterations will allow the zebrafish to complement what can be achieved in other models, such as mouse and human cell culture systems.

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Section: Zebrafish As a Cancer Modelmentioning

confidence: 99%

Zebrafish cancer: the state of the art and the path forward

2013

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“…Among 52 SRs, we selected two high-quality SRs, one each for biologics [9] and DMARDs [10]. Three more SRs including trials with DMARDs were added [5,11,12]. All randomized trials obtained from SRs were pooled and updated from January 2009 to July 2013 (Table 1, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Because of their high costs and long-term adverse effects, however, biologics have been under strict regulatory control in many countries, including Korea. One study showed that the majority of RA patients satisfying the American College of Rheumatology (ACR), British Society for Rheumatology, and Japan College of Rheumatology guidelines for use of the TNF-α blockers did not meet the Korean National Health Insurance reimbursement criteria [5]. Because the cost of biologics is much higher than traditional DMARDs, discretion in their use is warranted even in patients refractory to MTX.…”

Section: Introductionmentioning

confidence: 99%

“…Although some DMARD combinations, such as leflunomide or sulfasalazine with MTX, have been shown to be effective in RA patients not responding to MTX monotherapy [5], few studies have compared biologics and combination DMARDs head-to-head in patients refractory to MTX. In the absence of head-to-head trials with relevant comparators, it is possible to compare multiple treatment groups simultaneously by using all the outcomes from direct and indirect comparisons [6].…”

Section: Introductionmentioning

confidence: 99%

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Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison

Choi

Hyun

Choi³

et al. 2017

Korean J Intern Med

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Background/AimsBiological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to ‘traditional’ disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX).MethodsFour DMARDs (hydroxychloroquine, sulfasalazine, MTX, lef lunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, inf liximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC).ResultsIn total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively.ConclusionsBased on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.

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“…Таким образом, монотерапия лефлуномидом как для РА в целом [62], так и для раннего РА приводит к результатам, аналогичным монотерапии метотрексатом. В ряде крупных обзоров показано, что лефлуномид является БПВП для лечения РА с хорошей переносимо-стью и доказанной эффективностью, достаточно быстро снижая активность РА у большинства больных, тормозя рентгенологическое прогрессирование деструкции суставов и улучшая функциональный статус и качество жизни пациентов [34,54,[59][60][61].…”

Section: таблица результаты основных исследований эффективности лефлunclassified

Leflunomide in Early Rheumatoid Arthritis: Inclusion in the Treatment Strategy and Prospects

Каратеев¹,

Orlova²

2017

Med. sov.

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По данным литературы, лефлуномид сопоставим по эффективности и безопасности с метотрексатом, в том числе у паци-ентов с ранним ревматоидным артритом (РА). Препарат продолжает играть важную роль в лечении больных ранним РА и может рассматриваться в качестве основного синтетического базисного противовоспалительного препарата, который должен назначаться при невозможности терапии эффективными дозами метотрексата. Комбинация метотрексата и леф-луномида, уменьшая потребность в биологической терапии, может быть одним из эффективных способов преодоления толерантности к метотрексату. Роль данной комбинации в стратегии лечения раннего РА может быть недооценена, целе-сообразно продолжение исследований в этом направлении.Ключевые слова: ранний ревматоидный артрит, лефлуномид, метотрексат, стратегия лечения.

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Leflunomide in monotherapy of rheumatoid arthritis: meta‑analysis of randomized trials

Cited by 31 publications

References 35 publications

Zebrafish cancer: the state of the art and the path forward

Zebrafish cancer: the state of the art and the path forward

Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison

Leflunomide in Early Rheumatoid Arthritis: Inclusion in the Treatment Strategy and Prospects

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