Elsevier

Life Sciences

Volume 171, 15 February 2017, Pages 45-50
Life Sciences

Treatment of rheumatoid arthritis with combination of methotrexate and Tripterygium wilfordii: A meta-analysis

https://doi.org/10.1016/j.lfs.2017.01.004Get rights and content

Abstract

Aims

Extracts of Tripterygium wilfordii Hook F (TwHF), a traditional Chinese herbal medicine, have been widely used for treating rheumatoid arthritis (RA) in combination with methotrexate (MTX) in China for several decades. However, the efficacy and safety of MTX plus TwHF treatment remain unclear.

Main methods

A comprehensive search of databases in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors.

Key findings

Six randomized controlled trials were included in the final analysis with a total of 643 patients. All trials added TwHF (in the form of Tripterygium glycosides) to the MTX-based therapy. For efficacy, the addition of TwHF increased 50% responder rates (RR) (RR 1.337, 95% confidence interval [CI]: 1.188–1.505, P < 0.001), and it reduced swollen and tender joint counts, shortened the duration of morning stiffness, decreased the erythrocyte sedimentation rate, and decreased the level of C-reactive protein and rheumatoid factor. For safety, the addition of TwHF did not increase the rate of adverse events (RR 0.824, 95% CI: 0.635–1.068, P = 0.143).

Significance

MTX plus TwHF therapy may be a more effective and similar safe strategy for treating RA compared to MTX monotherapy. Further large clinical trials to investigate the TwHF add-on therapy are warranted.

Introduction

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that affects about 0.5–1.0% of the population, especially women and the elderly [1]. RA is characterized by systemic and synovial inflammation, and it leads to permanent joint damage and disability if uncontrolled. At present, synthetic disease-modifying anti-rheumatoid drugs (DMARDs), particularly methotrexate (MTX), are the first-line drugs to alleviate synovitis and systemic inflammation for treating RA [2]. Second-line immune-selective biologic agents (drugs) may be slightly more tolerable than synthetic DMARDs [3], [4]. However, the current pharmacologic therapies cannot produce an adequate response in many patients [5], and the new pharmacologic strategies for RA treatment are still warranted.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese medicine herb, and its root has been used to treat RA in traditional Chinese medicine [6]. TwHF extracts have been widely used and have even become a standard therapy in China for treating RA for several decades [7]. Increasing evidence has shown that TwHF extracts are efficacious for treating active RA, such as Tripterygium glycosides and triptolide [8], [9], [10]. Previous meta-analysis studies support that TwHF extracts are effective and safe for treating RA [11], [12]. In two small clinical trials, TwHF extracts also show good efficacy on RA on U.S. patients [13], [14]. Recently, several randomized control trials further indicated that the addition of TwHF may be able to achieve better effectiveness than DMARDs monotherapy (such as MTX) in patients with RA [15], [16]. Actually, MTX plus TwHF has been empirically used for treating RA in China for decades [17], [18]. However, the evidence for the MTX plus TwHF therapy for RA remains inadequate, and it is necessary to have a quantitative meta-analysis of the efficacy and safety of TwHF add-on therapy in patients with RA. Therefore, we performed a quantitative meta-analysis of the efficacy and safety of the combined use of TwHF with MTX for RA.

Section snippets

Literature search

Two authors independently performed a systematic search of PubMed, Web of Science, and Clinical Trials.gov for clinical trials up to April 8, 2016. Comprehensive searching was conducted using the terms (“Tripterygium”, “lei gong teng”, or “thunder god vine”) and (“rheumatoid arthritis”, “atrophic arthritis,” or “rheumatism”). In addition, we also searched Chinese databases, including Wan Fang Data, VIP, and CNKI, for Chinese-language studies using the terms “lei gong teng” (for Tripterygium),

RCT selection

The study selection process is depicted in Fig. 1. Notably, two RCTs were excluded because they used MTX at 15 mg/kg in the control group but MTX at 7.5 mg/kg and MTX plus TwHF groups [18], [22], while another one was excluded because it was not an RCT related to the MTX plus TwHF treatment [10].

Finally, six completed RCTs (n = 643) were included in the current meta-analysis [15], [16], [23], [24], [25], [26]. All six RCTs used TwHF in the form of Tripterygium glycosides, which is a tablet

Discussion

In recent decades, TwHF plus MTX has become a common strategy for treating RA in China. Here, we proved the systematic evidence that the MTX plus TwHF may be more effective than MTX monotherapy for treating active RA. For efficacy, the addition of TwHF increased both the improvement rate (30% response or ACR20) and effective rate (50% response or ACR50) compared to MTX monotherapy. The addition of TwHF also reduced the SJC and TJC, shortened the DMS, decreased the level of CRP and rheumatoid

Conclusion

The current study preliminarily indicated that MTX plus TwHF may be a more effective and similarly safe strategy for treating active RA compared with MTX alone. One included study also suggests MTX plus TwHF may be a more effective strategy for treating active RA compared with TwHF alone [15]. Further large clinical studies are still needed to investigate the long-term efficacy and safety of the addition of TwHF for treating RA.

Conflict of interest

None.

Acknowledgments

This work was funded by Zhejiang Provincial Natural Science Foundation of China (LY16H280005) and the National Natural Science Foundation of China (81673623), partly supported by “Xin Miao” Student Research Program of Zhejiang Province (2015R410052) and the Research Program of Zhejiang Chinese Medical University (2015ZG03).

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