Combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis

Ss, Lee; Yw, Park; Park, JJ; Ym, Kang; Ej, Nam; Kim, Shin Il; Jh, Lee; Wh, Yoo; Liu, Si

doi:10.1080/03009740802360632

Cited by 29 publications

(12 citation statements)

References 7 publications

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“…Administration of both MTX and LEF to rats with type II collagen-induced arthritis reduced serum levels of IL-17, receptor activator of NF-kB ligand (RANKL), and osteoprotegerin (OPG)37. Large cohort studies indicate that combination therapy with MTX and LEF is efficacious and safe in the treatment of active RA383940, and provides superior clinical benefits to MTX alone39. Therefore, we applied MTX and LEF combination therapy in this study.…”

Section: Discussionmentioning

confidence: 99%

IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide

Wang

Zhao

Liu

et al. 2017

Sci Rep

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T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22+CD4+T helper (IL-22+ Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22+ Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ−IL-17−IL-22+ (Th22), IFN-γ−IL-17+ (total Th17), IFN-γ+IL-17−IL-22+ (IL-22+Th1) cells, and IFN-γ−IL-17+IL-22+ (IL-22+Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders. Reductions in plasma IL-22 level significantly correlated with percentage of circulating Th22 cells and the decrease of plasma IL-22 level correlated with the reduction of DAS28 in responders. Our data suggests that circulating Th22 cells and plasma IL-22 level play a detrimental role in RA. The combination MTX+LEF therapy, by targeting Th22 cells and reducing IL-22 level, relieves the immune defects and ameliorates symptoms of RA. This study provides novel mechanistic understanding of the pathogenesis of RA, which may promote a design of better therapies for RA.

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Section: Discussionmentioning

confidence: 99%

IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide

Wang

Zhao

Liu

et al. 2017

Sci Rep

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“…Studies have shown that combinations of DMARDs are more effective than monotherapy. 14,15,16 In addition, biological agents are more effective when combined with DMARDs, in particular methotrexate. 17,18,19 This justifies the strategy of combining DMARDs or biological agents found in most patients in this study.…”

Section: Discussionmentioning

confidence: 99%

Potenciais interações medicamentosas em pacientes com artrite reumatoide

Bagatini¹,

Blatt²,

Maliska³

et al. 2011

Rev. Bras. Reumatol.

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Introduction: The term polypharmacy, meaning the concomitant use of multiple medications by one individual, has been widely reported in institutionalized or elderly patients. It can, however, occur in patients with chronic diseases, such as rheumatoid arthritis (RA). Objective: To quantify polypharmacy in a group of RA patients and to assess the risk of potential undesirable interactions between medications used for managing RA and those used for non-chronic diseases. Methods: A cohort study was carried out with 103 RA patients registered at the Strategy of Access to Medications from the Brazilian Health Ministry, at the School of Pharmacy of the city of Florianópolis, state of Santa Catarina. Patients were monthly followed up by use of form completion. Drug interactions were identified by use of the Drugdex System-Thomson Micromedex ®-Interactions database. Results: Polypharmacy was found in 95.1% of the patients, and 19 potential undesirable interactions were observed between the drugs used by 74 patients (mean of 3.0 ± 1.2 interactions/ patient). All potential interactions were related to methotrexate. Omeprazole was the major representative, accounting for 29.3% of the interactions, followed by diclofenac sodium (17.6%), and metamizole sodium (13.2%). Conclusion: Considering that this study confirms that polypharmacy is a common therapeutic practice in RA patients, it is worth emphasizing the need for greater surveillance regarding the adverse effects or effectiveness reduction of certain drugs due to drug interaction.

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“…В конце 1990-х -начале 2000-х гг. такая комбинация была достаточно широко распространена и продемон-стрировала достаточно отчетливый дополнительный положительный эффект по сравнению с монотерапией метотрексатом [70][71][72][73][74]. В то же время вероятность раз-вития нежелательных реакций (НР) на фоне такой комби-нации оказалась также существенно выше, чем при моно-терапии каждым из препаратов [75][76][77], что ограничивает применение этой комбинации на практике.…”

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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Combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis

Abstract: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents.

Cited by 29 publications

References 7 publications

IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide

IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide

Potenciais interações medicamentosas em pacientes com artrite reumatoide

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

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