Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with methotrexate in patients with rheumatoid arthritis: a randomized controlled trial

Abstract

Background: Biqi capsule is a traditional Chinese medicine widely used as a complementary and alternative treatment for rheumatoid arthritis (RA). The objective is to understand the efficacy, safety and mechanism of Biqi combined with methotrexate (MTX) in RA. Methods: We present a randomized, controlled pilot trial on Biqi combined with MTX against patients with active RA. Seventy patients were randomized 1:1 to receive Biqi + MTX or Leflunomide (LEF) + MTX for 24 weeks, and were assessed at baseline, 4, 12 and 24 weeks. Serum and urine samples were collected for metabolomics. Results: Overall, 81.2% patients in Biqi group achieved ACR20 at 24 weeks. No statistically significant differences were observed in primary or secondary outcomes between the two groups. A better safety profile was observed for Biqi with significantly fewer adverse effects reported (11.4%) compared to LEF group (40%, P < 0.05). Comparison between treatment responders and non-responders indicated a unique urine metabolic profile of enriched fatty acids and decreased acylcarnitines associated with Biqi responders, indicating a restored energy homeostasis in response to Biqi. The gene targets of these metabolites were significantly enriched in interleukin-4 and interleukin-13 pathways, implying that Biqi could ameliorate Th2-derived inflammatory response. Multivariate network analysis indicated that patient morning stiffness and SJC were key factors associated with metabolomics in Biqi-treated patients, whereas CRP was the main factor in LEF group. Therefore, Biqi and LEF likely work by influencing different patient clinical parameters. Conclusions: Our study suggests that Biqi capsule can be a promising alternative option in combination with MTX for RA treatment, and demonstrates the capability of using metabolomics to interrogate mechanism of action for traditional Chinese medicine. Trial registration This trial is registered with ChiCTR, No. ChiCTR-IPR-16009029. Registered August 15, 2016. http://www. chict r.org.cn/showp rojen .aspx?proj=15034

Efficacy of Bi Qi Capsules in combination with methotrexate in the treatment of rheumatoid arthritis

“…[ 6 ] Animal studies have found that BQC exerts a protective effect on articular cartilage by downregulating cartilage oligomeric matrix protein levels in serum, cartilage oligomeric matrix protein expression in synovium and cartilage, and inhibiting inflammatory infiltration, synovial proliferation, and joint destruction. [ 24 ] MTX is a commonly used DMARDs class of drugs in clinical practice, and clinical studies have demonstrated synergistic effects of MTX in combination with paralysis capsules, [ 11 , 13 ] but rigorous randomized, double-blind controlled studies to evaluate their long-term efficacy are lacking. Therefore, a prospective, randomized, double-blind, single-simulation randomized controlled study would be conducted to investigate the long-term efficacy and safety of BQC in combination with MTX compared to MTX alone in the treatment of RA.…”

“…[ 10 ] BQC is a commonly used Chinese materia medica preparation for the treatment of RA in China and has been approved by the State Food and Drug Administration as a complementary therapy for RA due to its good efficacy and low side effects. [ 11 ] BQC consists of Radix Notoginseng (San Qi), Strychni Semen (Ma Qian Zi), Codonopsis pilosula (Franch.) Nannf (Dang Shen), Rhizoma Atractylodis Macrocephalae (Bai Zhu), Radix Salviae Miltiorrhizae (Dan Shen), Rhizoma Chuanxiong (Chuan Xiong), and Radix Glycyrrhiza (Gan Cao), which have significant anti-inflammatory, antiswelling and analgesic effects.…”

“…[ 13 ] Some studies have found that the combination of BCQ with MTX for the treatment of RA improves the efficacy and promotes the improvement of clinical symptoms and inflammatory factor levels without increasing adverse effects. [ 11 ] However, a direct comparison of BQC combined with MTX vs MTX alone is lacking, and the short follow-up period fails to support the evaluation of the long-term efficacy of this combination regimen. Therefore, we proposed to evaluate the long-term efficacy and safety of BQC in combination with MTX in the treatment of RA in this randomized controlled trial.…”

Efficacy and safety of Biqi capsule in the treatment of knee osteoarthritis

“…It has the functions of nourishing qi and blood, dispelling wind and dehumidifying, promoting blood circulation, and relieving pain. Modern pharmacological research has found that, [ 14 ] Biqi capsule can promote the production of tissue inhibitor of metalloproteinase-1, reduce the expression of interleukin 1 and matrix metalloproteinase-3, so as to protect articular cartilage and improve inflammation, [ 15 ] it can also effectively regulate the ability of physical coordination and immune function, [ 16 ] and has less adverse reactions. [ 17 – 19 ] Therefore, we intend to evaluate the efficacy and safety of Biqi capsule in the treatment of KOA by this randomized controlled trial.…”

Metabonomic Study on the Plasma of High-Fat Diet-Induced Dyslipidemia Rats Treated With Ge Gen Qin Lian Decoction By Ultra High Performance Liquid Chromatography–Mass Spectrometry

“…In recent years, metabonomics has been widely used in the research of disease phenotype, biomarker discovery of drug toxicology, metabolism phenotype and physiological function of experimental animals, comprehensively depicting the overall characteristics of metabolism [23,24]. In order to study the metabolic mechanism of dyslipidemia and try to nd the key biomarkers in the intervention of Gegen Qinlian decoction on dyslipidemia.…”