Efficacy and safety of combined therapy with synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: Systematic literature review

Alén, Jaime Calvo; Pérez, Trinidad; Yuste, Susana Romero; Ferraz‐Amaro, Iván; Sancho, Juan José Alegre; Tasende, José Antonio Pinto; Pan, Francisco Maceiras; Quevedo, Juan Carlos; Hernández-Hernández, María; Calleja, Cristina Hidalgo; Álvarez, Alejandro San Martín; Sánchez, María Isabel Tévar; Sanmartí, Raimón

doi:10.1016/j.reumae.2018.07.010

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…The objective was to evaluate the ARC20 response at 24 weeks and found that 46.2% and 19.5% reached it, respectively [17]. Subsequently, the same team performed an open extension of this study, which followed 90 patients with the combination up to 48 weeks, obtaining an ACR20 response in 52.2% of the patients [16]. Other studies of lower level of evidence, such as that of the team of SS Lee et al, which aimed to analyze the percentage of patients who achieved the ACR20 response.…”

Section: Discussionmentioning

confidence: 99%

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Metothrexate Plus Leflunomide Step-Up Therapy in Early Rheumatoid Arthritis Patients with Non-Response to Initial Methotrexate Monotherapy

Carlevaris¹,

Citera²,

Pellet³

et al. 2019

Rheumatology

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Methods: We included a cohort of patients with diagnosis of early RA of less than 2 years of disease duration who not respond to MTX monotherapy, according to medical judgment, and added step-up combination with LEF. Data were collected every 3 months, including sociodemographic characteristics, functional status, disease activity and treatment. The primary outcome was the time to remission with the combined therapy, defined according to disease activity index of 28 joints (DAS28). Combination treatment failure was defined as not achieving remission. Time of outcome was assessed from date of the start of MTX plus LEF combination to date of remission or last follow-up. The Kaplan-Meier product limit method was used to estimate the probability of each outcome. Results: A total of 106 patients were included. The median disease duration was 4 (IQR 2-8) months. Median followup was 34 ± 18 months (300 patients-year). Mean age was 50 ± 12 years and 83% were female. At the time of LEF addition, 95 (90%) of patients were not in remission. During follow-up, 47 (50%) achieved clinical remission at a median time of 8 months. The rest of the patients failed to achieve remission. The overall probability of remission per patients-months of follow-up was 0.49. Twenty seven out of 47 patients (58%) were still in remission at the last follow up visit (median follow-up after first remission=19 months).

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Section: Discussionmentioning

confidence: 99%

“…Methotrexate (MTX) should always be considered the first therapeutic option in patients who do not have contraindications for its administration. Multiple studies have shown that approximately 50% of patients who start MTX achieve control of the disease [2,[14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Metothrexate Plus Leflunomide Step-Up Therapy in Early Rheumatoid Arthritis Patients with Non-Response to Initial Methotrexate Monotherapy

Carlevaris¹,

Citera²,

Pellet³

et al. 2019

Rheumatology

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“…[14][15][16][17] LEF has been successfully used in rheumatoid arthritis, lupus nephritis, and small vessel vasculitis. [25][26][27][28][29] In giant cell arteritis, which is also a type of large-vessel vasculitis with similar characteristics to TA, LEF treatment showed promising effects as a steroid-sparing agent and had a lower relapse rate, lower cumulative GC dose, and good safety. 30 However, evidence from large-sample, prospective, controlled studies supporting its efficacy and safety in TA is still lacking.…”

Section: Safetymentioning

confidence: 99%

Efficacy and safety of leflunomide versus cyclophosphamide for initial-onset Takayasu arteritis: a prospective cohort study

Sun

Cui

Dai

et al. 2020

Therapeutic Advances in Musculoskeletal

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Background: Leflunomide (LEF) has been considered as an alternative treatment for Takayasu arteritis (TA); however, data on its efficacy are still scanty. Objective: To investigate the efficacy and safety of LEF versus cyclophosphamide (CYC) for initial-onset TA. Methods: Initial-onset TA patients with active disease were enrolled in this research. Patients enrolled from 1 January 2009 to 31 December 2015 were treated with glucocorticoids and CYC, while patients enrolled from 1 January 2016 to 31 October 2018 received glucocorticoids and LEF. Treatment response including complete remission (CR), partial remission (PR), and effectiveness rate (ER) and side effects were evaluated at 6 and 12 months. Results and conclusion: In total, 92 patients were enrolled. A total of 47 patients were treated with LEF, while 45 patients were treated with CYC. The CR and ER rates were 75.55%, and 88.89% at 6 months, and 85.37% and 95.12% at 12 months in the LEF group. The CR and ER rates were 39.02% and 70.73% at 6 months, and 56.41% and 82.05% at 12 months in the CYC group. The CR rate was significantly higher in the LEF group than in the CYC group both at 6 months (75.61% versus 38.24%, p < 0.01) and 12 months (77.42% versus 53.33%, p < 0.05) after adjustment for propensity scores. The incidence of side effects in the LEF group was much lower than that in the CYC group (21.28% versus 44.44%). In conclusion, LEF provided a better treatment response, along with lower reproductive toxicity, compared with CYC in initial-onset TA.

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“…Current medical treatments for RA include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs [ 4 ]. Despite all these efforts to provide medical therapy for RA, a significant portion of RA patients remain unremitted despite the progression of treatment [ 5 , 6 ]. Therefore, it is crucial to understand the cellular and molecular processes by which the pathology is mediated in order to develop mechanism-driven therapeutic approaches for RA.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis

Zai

Zheng

et al. 2023

IJMS

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Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor−like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the regulatory role, clinical significance, and underlying mechanisms of circRNAs in RASF tumor−like growth and metastasis remain largely unknown. Differentially expressed circRNAs in synovium samples from patients with RA and patients with joint trauma were identified via RNA sequencing. Subsequently, in vitro and in vivo experiments were performed to investigate the functional roles of circCDKN2B−AS_006 in RASF proliferation, migration, and invasion. CircCDKN2B−AS_006 was upregulated in synovium samples from patients with RA and promoted the tumor-like proliferation, migration, and invasion of RASFs. Mechanistically, circCDKN2B−AS_006 was shown to regulate the expression of runt−related transcription factor 1 (RUNX1) by sponging miR-1258, influencing the Wnt/β−catenin signaling pathway, and promoting the epithelial−to−mesenchymal transition (EMT) in RASFs. Moreover, in the collagen−induced arthritis (CIA) mouse model, intra−articular injection of lentivirus−shcircCDKN2B−AS_006 was capable of alleviating the severity of arthritis and inhibiting the aggressive behaviors of SFs. Furthermore, the correlation analysis results revealed that the circCDKN2B−AS_006/miR−1258/RUNX1 axis in the synovium was correlated with the clinical indicators of RA patients. CircCDKN2B−AS_006 promoted the proliferation, migration, and invasion of RASFs by modulating the miR−1258/RUNX1 axis.

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Efficacy and safety of combined therapy with synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: Systematic literature review

Cited by 5 publications

References 29 publications

Metothrexate Plus Leflunomide Step-Up Therapy in Early Rheumatoid Arthritis Patients with Non-Response to Initial Methotrexate Monotherapy

Metothrexate Plus Leflunomide Step-Up Therapy in Early Rheumatoid Arthritis Patients with Non-Response to Initial Methotrexate Monotherapy

Efficacy and safety of leflunomide versus cyclophosphamide for initial-onset Takayasu arteritis: a prospective cohort study

Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis

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