Expert Consensus on the Treatment of Rheumatoid Arthritis with Chinese Patent Medicines

Abstract

Background:

Chinese patent medicines (CPMs) are widely used for the treatment of rheumatoid arthritis (RA) in China and especially by Western biomedical doctors who are not well trained in TCM. Thus, it is important to create a guideline or an expert consensus so that the CPMs are used correctly.

Methods:

The Delphi technique was used to generate the expert consensus. Twenty-eight (28) integrative medicine rheumatologists joined the consensus. A questionnaire regarding the general therapeutic principles, the categories, and the indications for the specific CPMs used for RA treatment was devised for this study.

Results:

More than 80% of the experts agreed on the following therapeutic principles: CPM could be used to treat all patients with RA (82.10%), CPM should be used under the guidance of Traditional Chinese Medicine (TCM) (100%), and CPM could be used for active RA treatment in combination with Western medicine (WM) (85.71%), but could be used alone (92.86%) for the treatment of inactive RA. In addition, CPM and WM should be taken separately (82.14%), although the CPM could reduce the side-effects of the WMs if used in combination with CPM (96.43%). For the treatment of active RA, the CPMs were recommended by more than 50% of the experts included the Leigongteng Duogan tablets (85.7%), Zhengqing Dengtongning tablets (64.3%), and Simiao pills (53.6%). Alternatively, for the treatment of inactive RA, Duhuo Jisheng mixture (71.4%), Yishen Juanbi pills (53.6%), and Wangbi electuary (50.0%) were recommended. Total paeonia glucoside capsules were recommended for the active (50.0%) and inactive RA (64.3%) treatment. The indications of each CPM were specified according to the symptoms related to the TCM pattern classification.

Conclusions:

This expert consensus regarding the treatment of RA with various CPMs was formed to aid WM doctors in the correct use of CPMs.

Introduction

R heumatoid arthritis (RA) is a chronic, inflammatory rheumatic disease characterized by joint pain, joint swelling, joint tenderness, and the destruction of synovial joints, which lead to severe disability and premature mortality.¹ Furthermore, mortality rates have been shown to be higher in patients with RA than in the general population.² Although the optimal use of disease-modifying antirheumatic drugs (DMARD),³ in particular the anchor drug DMARD methotrexate (MTX), as well as the availability of new biologic agents in recent decades have dramatically enhanced the success of RA treatment management,⁴ the side-effects and the economic burden for this treatment remain significant challenges for clinicians and patients.^5,6

In traditional Chinese medicine (TCM), RA is referred to as Bi syndrome, Lijie and Wangbi, which are types of arthrosis with the main symptoms of joint pain and swelling and paraesthesia.⁷ TCM has a long history of treating RA with Chinese herbal medicines (CHMs). In the past, TCM doctors have treated RA with herbal mixtures of sliced herbal materia medica (individually tailored polypharmacy formulas as water-based decoctions), which exert therapeutic actions and modulating effects.⁸ With the recent development of pharmaceutics, many classic CHMs have been developed to Chinese patent medicines (CPMs) after being approved by Chinese authorities. It has been estimated that there are dozens of CPMs on the market for the management of RA, and some of these have been tested in clinical studies and have been shown to have therapeutic actions for RA treatment.^9

–12 As a result, CPMs are widely used for RA treatment in China not only by integrative medicine (IM) doctors, but also by biomedical doctors, though TCM doctors do not prefer to use CPMs in the clinic. The method that combines the WM and TCM therapeutic regimens has been used in China for more than 50 years¹³ and has formed a new medical system that is known as IM, or integrated traditional and Western medicine. For the treatment of RA, IM doctors and biomedical doctors have often combined CHMs and Western medicine (WM). Study has shown that combined therapy is a common approach in clinical practice.¹⁴ However, CPMs are administered according to TCM pattern classification theory, which is difficult for biomedical doctors, who are not well trained in TCM, to understand and use correctly. Furthermore, there is no relevant clinical practice guideline or consensus on how to best administer CPMs. Therefore, the authors have formed a consensus on the use of CPMs to guarantee their optimal therapeutic use in the treatment of RA and have used comprehensible terminology to assist biomedical doctors in their proper use.

Participants and Methods

Participating experts

A clinical expert consensus management group was formed, and the IM rheumatologists in the Rheumatic Disease Division of the Chinese Association of Integration Medicine were included as the participants, since they were recommended and selected by a professional committee in China Association of Integrative Medicine to be accepted as the members in the division. Those who did not have more than 10 years of clinical experiences in RA treatment with CPMs and the publication of at least two peer-reviewed related articles were excluded in this study. All participants were approved by the China Association of Integrative Medicine. Twenty-eight (28) experts were qualified to join this consensus, and Table 1 shows general information regarding the participants.

Table 1.

General Information on the Experts Involving the Consensus (n=28)

General information	Number	Percentage (%)
Age
<40 yrs	1	3.6
40–50 yrs	13	46.4
50–60 yrs	10	35.7
>60 yrs	4	14.3
Academic position
Professor	21	75
Vice-professor	7	25
Clinical experience (years)
10–20 yrs	4	14.2
20–30 yrs	12	42.9
≥30 yrs	12	42.9

Consultation process

The Delphi technique was used to form the consensus, and three rounds of consultations were performed in this study. In the first round, the selected experts were asked to provide the general therapeutic principles regarding the use of CPMs and to list the common CPMs used clinically for RA management. Based on the suggestions of the experts, a general search of the Chinese pharmacopoeia (2005 edition), PubMed, Embase, CINAHL^®, Cochrane Library, Chinese CNKI, and Wanfang databases were conducted to identify whether the CPMs in question have been used in clinical practice. The results from the first round of consultation and the results from the literature review were submitted to the management group. Following a discussion, a questionnaire for the second round of the consultation was formed, which included the revised general therapeutic principles, and a list was suggested of CPMs based on the indications from the first round of the consultation. For the second round, items were automatically accepted if they were selected by more than 80% of the experts, whereas items receiving less than 20% of the experts' support were removed. The items that received positive agreement levels between 20% and 80% were recirculated to the third round. In the third round, the revised questionnaire and the results of second round were given to the experts for their selection.

Results

General practice recommendations obtained by the consensus

From the three rounds of consultation, 10 general therapeutic principles were established and 7 different types of CPMs were recommended for RA management (Fig. 1).

FIG. 1.

Scheme of the consensus for rheumatoid arthritis (RA) treatment with Chinese patent medicines (CPMs). C, consensus. TCM, Traditional Chinese Medicine; WM, Western medicine; LGTDG, Leigongteng Duogan; ZQFTN, Zhengqing Fengtongning; SM, Simiao; DHJS, Duhuo Jisheng; TGP, total glucosides of paeonia; YSJB, Yishen Juanbi; WB, Wangbi.

In the first round of consultation, the experts discussed 23 general therapeutic principles and 45 different types of CPMs for the treatment of RA (data not shown). In the second round, 2 general therapeutic principles were selected by more than 80% of the experts (Table 2) and were automatically accepted, 33 types of CPMs were selected by less than 20% of the experts and were removed, and 2 items regarding general principles were added. In the third round, 8 general principles regarding the use of CPM were selected by more than 80% of the experts (Table 2), and 7 types of CPMs were selected by 50% or more of the experts (Table 3).

Table 2.

Consensus on General Therapeutic Principles for Rheumatoid Arthritis (RA) Treatment with Chinese Patent Medicines (CPMs)

No.	Consensus	Round obtained	Percentage of experts selected
1.	Treatment of RA with CPMs is suitable for all of the RA patients	2nd	82.10%
2.	CPMs should be used with WMs together in active RA treatment	3rd	85.71%
3.	CPMs could be used alone in inactive RA treatment	3rd	92.86%
4.	CPMs and WMs should be taken separately when used together	3rd	82.14%
5.	The dosage of WMs could be decreased When combining with CPMs	3rd	88.46%
6.	CPMs could reduce the side-effect of WMs in RA treatment	2nd	96.43%
7.	Different kinds of CPMs should be used in different stage	3rd	100%
8.	CPMs should be used according to pattern differentiation theory of TCM	3rd	100%
9.	Do not take more than two kinds of CPMs at the same time	3rd	92.86%
10.	Doctors should monitor the change of symptoms to avoid side-effect of CPMs	3rd	80.77%

WMs, Western medicines.

Table 3.

Indication Related Symptoms and Possible Side-Effects of the Chinese Patent Medicines (CPMs) Listed in the Consensus

	Name (percentage of experts selected)	Indication related symptoms (percentage of experts selected)	Main side-effect symptoms (percentage of experts selected)
For active RA	LGTDG tablets (85.7%)	1. Heavy joint pain (91.67%)	1. Dysmenorrhea (61.54%)
		2. Swollen joints with skin redness and a hot feeling in the joints (75.00%)	2. Amenorrhea, dysgenesia (61.54%)
		3. Swollen joint only (62.50%)	3. Stomach discomfort (stomachache, nausea, emesis) (53.85%)
			4. Myelosuppression (aleukocytosis, thrombocytopenia) (53.85%)
	ZQFTN enteric tablets (64.3%)	Moderate joint pain (90%)	Rash (75%)
	SM pills (53.6%)	1. Swollen joints with skin redness and a hot feeling in the joints (93.75%)	No side-effect was found yet
		2. Moderate joint pain (75.00%)
		3. Joint pain with a hot feeling in the joints (68.75%)
For both active and nonactive RA	TGP tablet capsules (Active RA: 50.0%, inactive: 64.3%)	1. Moderate joint pain (100.00%)	Diarrhea (90.48%)
		2. Swollen joints (77.78%)
		3. Fatigue (55.56%)
For nonactive RA treatment	DHJS mixture (71.4%)	1. Moderate joint pain (95.00%)	No side-effect was found yet
		2. Fatigue (75.00%)
		3. Lumbago (75.00%)
		4. Swollen joint (65.00%)
		5. Cold feeling in the joints (60.00%)
	YSJB pills (53.6%)	1. Moderate joint pain (95.24%)	Stomach discomfort (stomachache, nausea, emesis) (100%)
		2. Joint swollen only (76.19%)
		3. Lumbago (80.95%)
		4. Fatigue (71.43%)
		5. Cold feeling in joints (61.90%)
	WB electuary (50.0%)	1. Swollen joint pain (78.95%)	Stomach discomfort (50%)
		2. Fatigue (63.16%)
		3. Swollen joint (57.89%)
		4. Lumbago (52.63%)

RA, rheumatoid arthritis; LGTDG, Leigongteng Duogan; ZQFTN, Zhengqing Fengtongning; SM, Simiao; TGP, total glucosides of paeonia; DHJS, Duhuo Jisheng; YSJB, Yishen Juanbi; WB, Wangbi.

Although there has been a long history of using CPMs for RA treatment in China, there were still general therapeutic principles that needed to be clarified during this consultation. With regard to the use of CPM therapy and the treatment of individual patients for RA management, most of the experts believed that CPM could be used for all patients (Consensus 1). However, it was thought that the usage should be different based on the RA stage. For the treatment of active RA, CPMs should be combined with WM (Consensus 2). However, when CPMs are used for inactive RA, they can be used alone (Consensus 3). RA is a chronic disease, and the disease activity changes during the different disease stages. Neither single therapeutic regimens nor combined WM therapies have been shown to provide sustained improvement.¹⁵ Therefore, adjunct therapy is needed to improve the therapeutic effect.¹² Many doctors have applied the techniques of WM to modify RA disease and have applied CPMs to modify the symptoms of RA in China.

When CPMs are used with WMs for the treatment of active RA, the dosage of the WMs should decrease and should be taken separately (Consensus 4, 5). For the treatment of RA, the IM approaches include the combined use of CHMs or CPMs with different kinds of WMs, such as DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDs), or steroids. Many studies have shown that combined treatments are more effective at controlling the disease and modifying the disease symptoms than single therapies.¹⁶ Furthermore, there have been studies that have shown CPMs or CHMs to reduce the side-effects of WM RA treatment,* and this was agreed upon by most of the experts (Consensus 6). For the complicated CPM components and the possible interactions of these treatments with WM, it may be desirable to separate these therapies in clinical practice.

For the management of RA at different stages of the disease, experts recommended that CPMs should be used under the guidance of the TCM pattern differentiation (Consensus 8) and that different CPMs should be used (Consensus 7) for RA with different TCM patterns. For cases with complicated TCM patterns, no more than two types of CPMs should be used together (Consensus 9). Moreover, it was recommended that practitioners should monitor changes in symptoms for the selection of other CPMs and should avoid the side-effects of CPM treatments (Consensus 10).

The types of CPMs that the experts recommended for different disease stages

With regard to therapeutic principles, the experts generally recommended that different types of CPMs should be used for different stages of the disease (Table 3). For the treatment of active RA, the recommended CPMs were the Leigongteng Duogan (LGTDG) tablets, the Zhengqing Fengtongning (ZQFTN) tablets, the Simiao (SM) pills, and the total glucosides of paeonia (TGP) capsules. For the treatment of inactive RA, the recommended CPMs were the Duhuo Jisheng (DHJS) mixture, the TGP capsule, the Yishen Juanbi (YSJB) pill, and the Wangbi (WB) electuary. TGP was the only CPM that was recommended for the treatment of both active and inactive RA. The general information about the selected 7 CPMs is shown in Table 4.

Table 4.

General Information of the Chinese Patent Medicines (CPMs) Listed in the Consensus

Name	Information source	Compositions	Specification	Directions
Leigongteng duogan (LGTDG) tablets	SFDASDADN&: Z42021212	Tripterygium wilfordii Hook F. (TwHF)	10 mg/tablet	1–1.5 mg/kg; t.i.d.; p.c.
Zhengqing fengtongning (ZQFTN) tablets	Chinese Pharmacopoeia 2010 edition & SFDA; SDADN:Z43020278	Sinomenine (SIN)	20 mg SIN/tablet	1–4 tablets; t.i.d; a.c.
Total glucosides of paeonia (TGP) capsules	SFDASDADN:H20055058	TGP	0.3 g/capsule (more than 104 mg)	0.6 g/t; t.i.d.
Simiao (SM) pills	Chinese Pharmacopoeia 2010 edition & SFDA; SDADN: Z22024960	Rhizoma Atractylodis, Lanceae (Cang zhu), Radix Achyranthis Bidentatae (Huai niu xi), Cortex Phellodendri Amurensis (Huang bai), Semen Coicis (Yi yi ren)	15 pills/g	6 g/t; b.i.d.
Duhuo jisheng (DHJS) mixture	Chinese Pharmacopoeia 2010 edition & SFDASDADN: Z51021514	Radix Angelicae (Du huo), Herba Taxilli (Ji sheng), Largeleaf Gentian Root (Qin jiao), Radix Saposhnikoviae (Fang feng), Herba Asari Mandshurici (Xi xin), Radix Angelicae sinensis (Dang gui), Rhizoma Chanxiong (Chuan xiong), prepared Rhizome of Rehmannia (Shu di), Radix Paeoniae Alba (Bai shao), Rumulus Ginnamomi (Gui zhi), Radix Cyathulae (Chuan niu xi), Cortex Eucommiae Ulmoidis (Du zhong), Radix Codonopsis (Dang shen), Poria (Fu ling), and Radix Glycyrrhizae (Gan cao)	20 mL/bottle	20 mL/t; t.i.d.
Yishen juanbi (YSJB) pills	SFDASDADN:Z10890004	Rhizoma Drynariae (Gu sui bu), Radix Rehmanniae praeparata (Shu di), Radix Rehmanniae (Sheng di), Radix Angelicae sinensis (Dang gui), Radix seu Herba Cynanchi Paniculati (Xu chang qing), Eupolyphaga (Tu bie chong), Bombyx Batryticatus (Jiang chan), Scolopendra (Wu gong), Scorpio (Quan xie), Cistanche deserticola (Rou cong rong), Nidus Vespae (Feng fang), Pheretima Aspergillum (Guang di long), zaocys (Wu shao she), Rhizoma Corydalis Yanhusuo (Yan hu suo), Herba Pyrolae Callianthae (Lu xian cao), Herba Epimedii Brevicornus (Yin yang huo), Herba Aristolochiae Mollissimae (Xun gu feng), Herba Humuli Scandentis (Lu cao), Caulis Spatholobi (Ji xue teng), Rhizoma Polygoni Cuspidati (Hu zhang) and Erodium stephanianum willd (Lao he cao)	8 g	8–12 g/t; t.i.d.
Wangbi (WB) electuary	Chinese Pharmacopoeia 2010 edition & SFDASDADN: Z20044060	Radix Rehmanniae praeparata (Shu di), Radix Rehmanniae (Sheng di), Himalayan Teasel Root (Xu duan), processed Radix Aconiti Lateralis Preparata (Zhi fu zi), Radix Angelicae Biserratae (Du huo), Rhizoma Drynariae (Gu suibu), Rumulus Ginnamomi (Gui zhi), Herba Epimedii Brevicornus (Yin yang huo), Radix Saposhnikoviae (Fang feng), Radix et Rhizoma Clematidis Chinensis (Wei lingxian), Spina Gleditsiae (Zao jiaoci), Radix Paeoniae Alba (Bai shao), Rhizoma Cibotii (Gou ji), Rhizoma Anemarrhenae (Zhi mu), Herba Lycopodii Japonici (Shen jincao), Flos Carthami (Hong hua), and goat bone (Yang gu)	6 g	6 g/t; t.i.d.

SFDA, State Food and Drug Administration. Website: www.sda.gov.cn/WS01/CL0001/; SDADN, State Drug Approval Document No.; /t, each time; p.c., post cibum; a.c., ante cibum or before meals.

The indications and side-effects of CPMs that the experts recommended

For the management of RA, experts recommended that CPMs should be used under the guidance of the TCM pattern differentiation. It was illustrated in this consensus that different types of CPMs have different indications of symptoms. Also, experts selected the possible clinical side-effects of the CPMs.

Table 3 shows the indication-related symptoms and possible side-effects of the CPMs listed in the consensus. The LGTDG was suggested to treat RA with the symptoms of heavy joint pain (91.67%), swollen joints with skin redness and a hot feeling in the joints (75.00%), or swollen joints only (62.50%), and its side-effects included dysmenorrhea (61.54%), amenorrhea (61.54%), dysgenesia (61.54%), stomach discomfort (53.85%) and myelosuppression (53.85%). The ZQFTN tablet was suggested to treat RA with moderate joint pain (90%), and its side-effect was rash (75%). The SM pill was suggested to treat RA with swollen joints with skin redness and a hot feeling in the joints (93.75%), moderate joints pain with a hot feeling in the joints (90%), and the experts suggested that it had no obvious side-effects. The DHJS mixture was suggested to treat RA with moderate joints pain (95.00%), fatigue (75.00%), lumbago (75.00%), swollen joints (65.00%), and a cold feeling in the joints (60.00%), and it did not have obvious side-effects. The YSJB pill was suggested to treat RA with moderate joints pain (95.24%), swollen joint (76.19%), lumbago (80.95%), fatigue (71.43%), and a cold feeling in the joints (61.90%), and it had the side-effect of stomach discomfort (100%). WB electuary was suggested to treat RA with moderate joint pain (78.95%), fatigue (63.16%), swollen joints (57.89%), and lumbago (52.63%), and it had the side-effect of stomach discomfort (50%). The TGP capsule was suggested to treat both active and inactive RA, and it can be used to treat RA with moderate joint pain (100%), swollen joints (77.78%), and fatigue (55.56%), and it had the side-effect of diarrhea (90.48%).

Discussion

The evidence-based medicine movement has had a major influence on the improvement of clinical practice. However, the implementation of this approach has encountered major difficulties when there has not been enough evidence, and CPM application in China is an example of this situation. Although CPM therapies have been used in randomized controlled trials and cohort studies, these have not been sufficient for the development of therapeutic guidelines. The CPM treatments do, however, possess considerable local practice experience, and therefore, it was chosen to utilize the Delphi technique to harness these experiences.

As a consensus method, the Delphi technique has proven to be useful at providing an evidence base for situations where there is insufficient evidence. Moreover, it has provided a way to systematically extract the expertise of people working in one area and has offered evidence that is readily applicable for a particular country and culture.¹⁷ It is also a well-recognized research method for the formation of a consensus among a group of experts through several iterations of a questionnaire.¹⁸ The advantages of this technique include the anonymity of the participants, which avoids dominance, the fact that the consensus is reached by summary measures, and the iterations that include controlled feedback, which allow individuals to change their opinion in light of the group's response. The Delphi technique takes full advantage of both the research and the clinical experience of the experts involved and also imposes no geographical limitations on participation.¹⁹

To guarantee that the doctors consulted had sufficient experience with CPM treatments as well as these in combination with WM, IM rheumatologists were chosen as the Delphi respondents. These doctors commonly treat RA with combined TCM and WM therapies and have enough experience to judge the use of CPMs alone or combined with WM. Furthermore, they have two medical educational backgrounds that contribute to their ability to explain the TCM terms and therapies in a manner that is comprehensible for biomedical doctors. The experts were from the members of the Division of Rheumatic Disease, Chinese Association of Integrative Medicine, and they were from nationwide and in accordance with the following principles: the 28 experts were from 16 provinces in the East, West, North, and South of China; they had more than 10 years of clinical experience in RA treatment to ensure significant clinical experience; they had published at least two peer-reviewed-related articles to ensure their scholarly level. TCM doctors in China often used herbal decoctions instead of CPM application in their clinical practice, and thus TCM doctors did not include this treatment in this consultation.

Compared to the classical TCM guidelines or the consensus that focused on solely on the TCM pattern differentiation, the target audience for this study's consensus was mainly biomedical doctors who had not been educated in TCM theory. This study did not focus on how to apply the complicated TCM pattern differentiation theory to the management of RA. Instead, the focus was on some general symptoms that have been used for TCM pattern classification and that can be understood by both TCM and WM doctors. Besides the main RA symptoms of joint pain and morning stiffness, patients also experience many other concomitant symptoms, such as hot or cold feelings in the joints, thirst, vexation and turbid yellow urine, which could be important for TCM pattern differentiation. Our previous studies have demonstrated the relationship between RA disease and TCM pattern.²⁰ In this study, the TCM pattern characteristics were not included, but those symptoms were listed as part of the indications for the use of CPMs in RA management to aid the evaluation of the biomedical doctors.

There have some pharmacology and clinical studies about those selected seven CPMs. The LGTDG tablet originates from the roots of Tripterygium wilfordii Hook F. (TwHF, known in China as Lei gong teng). It has been demonstrated that TwHF has immunosuppressive and anti-inflammatory activity.^21,22 Clinical studies have shown that its rate of effectiveness in RA treatment is between 60% and 90%.^23,24 Side-effects following the use of TwHF have been reported and include dysmenorrhea, oligospermatism, and adverse kidney function, which affect the recommended use of this compound for patients.¹³ The ZQFTN tablet consists of sinomenine (SIN), which is an alkaloid that is isolated from Caulis Sinomenii (known in China as Qing feng teng). A systematic review showed that the SIN was found to be more effective at the improvement of morning stiffness, joint pain, and the erythrocyte sedimentation rate.¹¹ The side-effect of this treatment is erythra, which has been recorded in the pharmacopoeia and has been previously reported elsewhere.²⁵ One (1) clinical study demonstrated that pure SIN had significant therapeutic effects on patients with RA,²⁶ and pharmacological studies have shown that it has anti-inflammatory and immunosuppressive properties.²⁷ One (1) possible mechanism responsible for the effect of SIN treatment in RA could be its inhibitory effect on cell invasion and migration.²⁸ The SM pill is generally used to treat active RA.²⁹ Clinical studies have shown that the DHJS mixture has anti-inflammatory therapeutic effects, which modify the symptoms and improve the joint function in RA.^30,31 The YSJB pill has been shown to have the clinical therapeutic effects that include the amelioration of clinical symptoms and signs, a decreased erythrocyte sedimentation rate, and lower levels of C-reaction protein and degree of rheumatic factor (RF) dripping.^16,32,33 Treatment with the WB electuary has demonstrated therapeutic effects in clinical research, including anti-inflammatory effects and the amelioration of clinical symptoms and signs.³⁴ The indicated symptoms for its application include light joint pain, fatigue, swollen joints, and lumbago, and most doctors believe that its application does not have side-effects. The TGP capsule has been shown to have anti-inflammatory and immunoregulatory properties,³⁵ and the possible mechanism of action could be its regulation of the cyclic adenosine monophosphate–dependent EP (2)/EP (4)-mediated pathway.³⁶ Also, one study has shown that the use of TGP reduced the hepatotoxicity of MTX and that there was a quicker treatment initiation with fewer side-effects and greater compliance when these treatments were used together.³⁷ Altogether, the studies could partially supply some scientific evidence for their role in the management of RA.

However, there are some limitations in this study. First, the existence of many CPMs for the management of RA that have indications for use based on TCM patterns, as well as the lack of rigorous clinical trials have made this consensus difficult to reach. In this study, three rounds of consultations were conducted, and those components were selected that were agreed upon by more than half of the experts. Second, the fact that many of the indications for the CPMs have been made using the TCM pattern has caused difficulties and made this consensus hard to understand. It has been acknowledged that the TCM pattern classification should be based on symptoms, signs, tongue appearance, and pulse feelings. In this study, the authors have selected the easy-to-comprehend symptoms/signs, which are important for the TCM pattern classification, as the indicated symptoms/signs for CPM application. However, tongue appearance and pulse feeling were not included in the list of indicated specifications for CPMs. It is believed that with the development of new instruments for tongue and pulse feeling, the tongue and pulse diagnosis could become an important part in the indication for the CPMs. Finally, although the IM doctors had experience in the application of CPMs for RA management, they did not understand TCM theory at this level of experience. It is hoped that as more doctors are trained in TCM and apply CPMs for clinical practice, the expert consensus for the application of CPMs will be of higher quality.

Conclusions

In conclusion, the Delphi technique was used to form an expert consensus on the treatment of RA with CPMs. The general therapeutic principles and the symptom indications for the use of different CPMs for RA treatment were obtained in this consensus. This consensus should be easily understood by WM doctors, and it should help them to use CPMs correctly for RA management.

Footnotes

Acknowledgment

We thank all the IM rheumatologists who took part in the consultation. This research is supported in part by the international cooperation project of the Ministry of Science and Technology of PRC (No. 2006DFA31770), National Natural Science Foundation of China for Distinguished Young Scientists (No. 30828047).

Disclosure Statement

No financial conflicts exist.

*

He YT. Study on the treatment project of Rheumatoid Arthritis [Dissertation]. Guangdong:Guangzhou University of Chinese Medicine; 2005:63.

References

Aletaha

, Neogi

, Silman

et al. Rheumatism collaborative initiative Rheumatology/European League Against an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis, 2010; 69:1580–1588.

Pieringer

, Pichler

. Cardiovascular morbidity and mortality in patients with rheumatoid arthritis: Vascular alterations and possible clinical implications. QJM, 2011; 104:13–26.

Visser

, van der Heijde

. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: A systematic review of the literature. Ann Rheum Dis, 2009; 68:1094–1099.

Doan

, Massarotti

. Rheumatoid arthritis: An overview of new and emerging therapies. J Clin Pharmacol, 2005; 45:751–762.

Edwards

, Leak

. Pericardial effusions on anti-TNF therapy for rheumatoid arthritis: A drug side effect or uncontrolled systemic disease? Rheumatology (Oxford), 2009; 48:316–317.

Karaca-Mandic

, Joyce

, Goldman

, Laouri

. Cost sharing, family health care burden, and the use of specialty drugs for rheumatoid arthritis. Health Serv Res, 2010; 45:1227–1250.

Zhang

, Dong

, Zhou

. Internal Medicine of TCM. 1st rev.. Shanghai: Scientific and Technical Publishers, 1985; 263P.

Wang

, Cai

, Kong

et al. A computer method for validating traditional Chinese medicine herbal prescriptions. Am J Chin Med, 2005; 33:281–297.

, Liu

. A review of experimental researches in Chinese traditional patent medicines for rheumatoid arthritis. China J Trad Chin Med Pharmacy, 2010; 25:1846–1849.

10.

, Shen

, Long

. Clinical research progress of rheumatoid arthritis treatment using Chinese formulated products. Chin Arch TCM, 2008; 26:1974–1976.

11.

, Liu

, Qi

et al. Sinomenine versus NSAIDs for the treatment of rheumatoid arthritis: A systematic review and meta-analysis. Planta Med, 2008; 74:1423–1429.

12.

Goldbach-Mansky

, Wilson

, Fleischmann

et al. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: A randomized trial. Ann Intern Med, 2009; 151:229–240.

13.

Chen

, Lu

. Situation of integrative medicine in China: Results from a national survey in 2004. Chin J Integr Med, 2006; 12:161–165.

14.

, Lu

, Zha

et al. Correlations between symptoms and ACR20 efficacy in 396 cases of rheumatoid arthritis. J Clin Rheumatol, 2007; 13:317–321.

15.

Ferraccioli

, Salaffi

, Nervetti

et al. Slow-acting drugs outcome is no different than 15 years ago. J Rheumatol, 1990; 17:1249–1250.

16.

, Lu

, Zha

et al. Differential effect on symptoms treated with traditional Chinese medicine and western combination therapy in RA patients. Complement Ther Med, 2008; 16:206–211.

17.

Minas

, Jorm

. Where there is no evidence: Use of expert consensus methods to fill the evidence gap in low-income countries and cultural minorities. Int J Ment Health Syst, 2010; 21,4:33.

18.

Myers

, Thomas

, Dziedzic

. What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study. BMC Musculoskelet Disord, 2010; 11:178.

19.

Jones

, Hunter

. Consensus methods for medical and health services research. BMC, 1995; 311:376–380.

20.

, Zha

, Chang

et al. Pattern differentiation in Traditional Chinese Medicine can help define specific indications for biomedical therapy in the treatment of rheumatoid arthritis. J Altern Complement Med, 2009; 15:1021–1025.

21.

Qiu

, Kao

. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D, 2003; 4:1–18.

22.

Tao

, Lipsky

. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin North Am, 2000; 26:29–50.

23.

Chen

K J

, Chen

. Achievements in clinical research of treating internal diseases with traditional Chinese medicine in recent years. Chin Med J (Engl), 1989; 102:735–739.

24.

Gao

, Zang

, Bai

. Radix Tripterygium Wilfordii Hook F in rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis. Chin Med J (Engl), 1986; 99:317–320.

25.

Okuda

, Umezawa

, Ichikawa

et al.

A case of drug eruption caused by the crude drug Boi (Sinomenium stem/Sinomeni caulis et Rhizoma)

J Dermatol, 1995; 22:795–800.

26.

Liu

, Liu

. Clinical observation on treatment of rheumatoid arthritis with zhengqing fengtongning retard tablets: A report of 60 cases. Zhong Xi Yi Jie He Xue Bao, 2006; 4:201–202.

27.

The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro. Life Sci, 2005; 77:3197–3209.

28.

, Li

et al. Sinomenine reduces invasion and migration ability in fibroblast-like synoviocytes cells co-cultured with activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, CD147. Rheumatol Int, 2011; 31:1479–1485.

29.

Zhang

, Zhang

. Clinical observation study on treatment of rheumatoid arthritis with modified Simiao pill: A report of 92 cases. Hebei J TCM, 2002; 24:917–918.

30.

Yang

, Song

. Clinical observation on treatment of rheumatoid arthritis with DHJS prescription: A report of 68 cases. Shanxi J TCM, 2010; 31:439–440.

31.

. Clinical observation on treatment of rheumatoid arthritis with DHJS prescription: A report of 58 cases. J Liaoning Med University, 2009; 30:240.

32.

Perera

, Peng

, Lu

et al. Effects of Yishen Juanbi (YJB) pill on experimental rheumatoid arthritis. Chin J Nat Med, 2010; 8:0057–0061.

33.

, Hu

, Jing

. Therapeutic effect of Yi Shen Juan Bi pill on rheumatoid arthritis. Zhejiang J Clin Med, 2008; 10:628–629.

34.

Yang

, Ji

, Cao

et al.

Clinical study of Wangbi pills in the treatment of rheumatoid arthritis (yin deficiency in liver and kidney, blood stasis stagnation syndrome)

Mod Trad Chin Med, 2009; 29:21–23.

35.

Zheng

, Wei

. Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes. Int Immunopharmacology, 2005; 5:1560–1573.

36.

Chang

, Wei

, Zhang

, Xu

. Effects, mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis. J Ethnopharmacol, 2009; 121:43–48.

37.

Wang

, Xing

. Clinical observation on effect of total glucosides of paeony combined with methotrexate on rheumatoid arthritis. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2007; 27:839–840.