Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study

Abstract

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5–15 mg weekly. The maintenance dose was 2.5–7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5–1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Appendices

Appendix 1: The clinical trial centers in the trial

Guangdong Provincial Hospital of Traditional Chinese Medicine, China-Japan Friendship Hospital, Guang An Men hospital of China academy of Traditional Chinese Medicine, Long Hua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Traditional Chinese Medicine of Hubei Province, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, First Affiliated Hospital, Tianjin College of Traditional Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine and Nantong Liangchun Clinical Research Institute of Traditional Chinese Medicine.

Appendix 2: The Tripterygium wilfordii multiglycoside tablet was administrated in the following way

• 1. Starting dose: 10 mg tid;

• 2. When mild adverse reactions such as slight gastrointestinal side reaction, menstrual disorder, facial flush and skin itching occurred, the dose is reduced to 10 mg bid;

• 3. When clinical evidence of progressive injuries of the liver, gastrointestinal tract, amenorrhea occurred, the dose is reduced to 5 mg bid;

• 4. When serious toxicity such as severe gastrointestinal side reaction, amenorrhea, serious hepatic dysfunction occurred, the drug is discontinued.

Appendix 3 [4, 5]

Bi syndrome (痹病) is a disorder resulting from the obstruction of meridians, sluggishness of qi and blood circulation after the invasion of exterior/interior pathogenic wind, cold, dampness or heat. It manifests as pain, soreness, aches, numbness or heaviness of muscles, sinews, and joints, and/or swelling and burning pain.

RA subjects randomized to the TCM treatment groups are further subdivided into the four syndromes of Bi syndrome (痹病) as listed below.

• 1. Cold Damp (Hanshibi 寒湿阻络型): A syndrome that arises when the movement of qi and blood is impeded by cold and dampness in combination. It is marked by cold pains with inconvenient flexion in joint and muscle and intolerance of cold. The pain improves with warmth. The tongue may be enlarged and have white slimy or white greasy coat. The pulse may be wiry slippery or tense pulse.

• 2. Damp Heat (Shirebi 湿热阻络型): A syndrome caused by a combination of dampness and heat, with manifestations of inflamed hot pain or swollen and stiff in joint and muscle. The tongue may be red and have off-white or yellow greasy coat. The pulse may be rapid and soft or rapid and slippery or wiry.

• 3. Cold Heat (Hanrebi 寒热错杂型): A syndrome that local symptoms characterized by cold 15 syndrome, and general symptoms by heat syndromes or local symptoms characterized by heat syndrome, and general symptoms by cold syndromes. The tongue coat may be white or yellow. The pulse may be string-like and/or rapid.

• 4. Liver and Kidney Deficiency and Meridian-Phlegm Stagnancy (肝肾亏损兼痰瘀阻络型): A syndrome that characterized by a long-term course with distortion and stabbing pain or numbness/ache in joint, muscle and bone. It may be purple tongue or purple spots on the tongue. The pulse may be weak (deep, fine, soft, thready) or hidden (not obvious, very deep).

Appendix 4

Drug name	Manufacturer	Main components
Tripterygii totorum (雷公藤多甙片)	WuHan pharmaceutical factory	Triptolide (50 µg in one tablet)
Yishen juanbi tablet (益肾蠲痹丸)	Qingjiang Pharmaceutical Factory of Jiangsu Province	Davallia, Radix Rehmanniae Preparata., Cynanchi Paniculati Radix Et R., Eupolyphaga seu Steleophaga, Nidus Vespae Honeysuckle Flower, Pheretima, Epimedium brevicornu Maxim, Kadsura interior, et al.
Hanshibi granule (寒湿痹颗粒)	Dalian Changbaishan Pharmaceutical Co., Ltd.	Radix Aconiti Lateralis Preparata, Radix Aconiti, Astragalus membranaceus, CassiaTwig, Atractylodes macrocephala Koidz., Radix Angelica Sinensis, Chaenomeles sinensis (Thouin) Koehne, Ephedra minuta Florin, et al.
Hanrebi granule (寒热痹颗粒)	Dalian Changbaishan Pharmaceutical Co., Ltd.	CassiaTwig, Radix Paeoniae Alba, Anemarrhena asphodeloides Bung, Ephedra minuta Florin, et al.
Granule for Arthralgia (尪痹颗粒)	Dalian Changbaishan Pharmaceutical Co., Ltd.	Radix Rehmanniae Preparata, Radix Dipsaci, RadixAconitiLateralisPreparata, Araliafargesii Franch, Davallia, CassiaTwig, Divaricate Saposhnikovia Root, Epimedium brevicornu Maxim, Rhizoma Cibotii, Lycopodii Herba, et al.