Editorial

Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Washington University Library on 01/11/15 For personal use only.

Traditional Chinese medicine: potential for clinical treatment of rheumatoid arthritis Expert Rev. Clin. Immunol. 10(7), 819–822 (2014)

Kamal D Moudgil Author for correspondence: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore St, HSF-1, Suite 380, Baltimore, MD 21201, USA [email protected]

Brian M Berman Center for Integrative Medicine, University of Maryland School of Medicine, 520 W. Lombard Street, East Hall, Baltimore, MD 21201, USA

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease affecting people worldwide. Increasing numbers of RA patients in the west are resorting to various complementary and alternative medicine modalities for relief of symptoms and well-being. Herbal products and acupuncture representing traditional Chinese medicine (TCM) are two of the most commonly used forms of complementary and alternative medicine. Frequently, their efficacy against RA and safety have been inferred from anecdotal experience or pilot testing on a relatively small number of patients following inadequate study designs. Accordingly, significant efforts need to be invested in objectively testing TCM in clinical trials that are sufficiently powered, randomized, blinded, possess appropriate controls and follow standard criteria for assessment of the outcomes. In addition, the mechanisms underlying the immunomodulatory and other antiarthritic activities of TCM modalities need to be better defined. These efforts would help validate the scientific rationale for the use of TCM for the management of RA.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints, which can lead to deformities and disability [1]. The disease affects about 1% of the global population and the prevalence of RA in women is about three-times higher than that in men. Both genetic and environmental factors play a role in the pathogenesis of RA. Many potent antiarthritic drugs are available for the management of arthritis. However, their prolonged use is associated with severe adverse effects and they are ineffective in a proportion of patients. In addition, they are expensive. Accordingly, an increasing number of patients with RA and other diseases in developed countries are using natural products and other complementary and alternative medicine (CAM) approaches for their healthcare needs [2–6]. These CAM products and services belong to various traditional systems of medicine, such as traditional Chinese medicine (TCM). However, despite the gradually

increasing popularity of CAM in the west, there is skepticism in the minds of the professionals practicing conventional medicine about the scientific validity of these CAM products and services [6,7]. TCM has been practiced in China for thousands of years and it offers a holistic approach to patient management. Herbal products and acupuncture are the most commonly used forms of TCM, which also includes moxibustion, tai chi and other modalities [5]. The application of TCM in RA is based on the categorization of patients according to distinct TCM patterns of Bi syndrome, based on cold and hot patterns, the level of vital energy (Qi) and other criteria. This is quite different from the criteria used to assess treatment efficacy in the western system, for example, the American College of Rheumatology (ACR) criteria. Accordingly, there is a need to integrate the parameters of the two systems for reliably assessing the efficacy of herbal treatment or acupuncture in RA patients.

KEYWORDS: acupuncture • complementary and alternative medicine • herbal therapy • immunology • inflammation • natural products • osteoarthritis • rheumatoid arthritis • traditional Chinese medicine • traditional systems of medicine

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10.1586/1744666X.2014.917963

Ó 2014 Informa UK Ltd

ISSN 1744-666X

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Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Washington University Library on 01/11/15 For personal use only.

Editorial

Moudgil & Berman

A variety of herbs belonging to TCM have been used in China for centuries for the treatment of rheumatic diseases, including RA. The anti-inflammatory and antiarthritic activities of many Chinese herbs have been validated in experimental models of arthritis and tested in clinical trials in RA patients [8–11]. However, the majority of clinical trials on herbal products suffer from deficiencies either in the quality of the test product or in the experimental design, or both [5,10–12]. Variations in the composition or potency of the herbal formula might in part be owing to geographical or seasonal variations. Limitations in the experimental design often include one or more of the following: small sample size, inadequate control groups or lack of randomization, absence of clearly defined inclusion/exclusion criteria, lack of blinding, inconsistency in the criteria for assessment of the outcomes and inadequate statistical analysis. Boswellia, tripterygium and celastrus represent a few of the many herbal remedies for RA in TCM. Among the herbal TCM trials, those using Tripterygium wilfordii hook F (TwHF) (aka Thunder God Vine) are perhaps the most reliable [10,12,13]. These were done using a well-characterized herbal extract and tested in randomized controlled trials. TwHF extract has been shown to be effective in RA, and interestingly, TwHF treatment over 24 weeks showed higher efficacy than sulfasalazine, a conventionally used drug, as assessed by attainment of ACR20 response criteria [13]. Moreover, treatment with TwHF resulted in a significant reduction in serum IL-6, a proinflammatory cytokine involved in RA pathogenesis. However, the use of TwHF was associated with a few serious side effects. Another recently reported study comparing TwHF with methotrexate (MTX) showed that TwHF was as effective as MTX and the combination of the two was better than MTX alone in controlling the disease activity in RA patients [14]. However, TwHF has not yet gained broader application. Two aspects of herbal remedies deserve some caution: safety and interactions with conventional medications. It is natural to assume that TCM herbs are not toxic, otherwise their use would not have been continued for so long. However, from time to time, cases of severe toxicity of Chinese herbs have been reported, including those owing to contaminated herbs [6]. With the increasing ease of purchase of over-the-counter natural products from vendors globally, it is difficult to fully ensure the safety of such products, which are not as rigorously regulated as conventional drugs. Another aspect of herbal use is the unanticipated interactions of herbs with conventional drugs [6,11]. Many patients consume herbal TCM products without the knowledge of their primary physician or rheumatologist. In this context, patients should be educated and encouraged to share information about their use of TCM or other CAM modalities with their physician. However, this would only be possible if there is no stigma attached to the use of CAM products. Acupuncture is another TCM modality that has thousands of years of history behind it and has been used widely for a variety of illnesses, including rheumatic diseases [5,11,15]. It involves the use of fine needles to puncture the skin and 820

stimulate specific points on defined channels (meridians) believed to be carrying vital information. Two main categories of acupuncture in use are electroacupuncture and traditional Chinese acupuncture. The diagnostic approach and treatment regimens for acupuncture (number of needles to be used, location of points for stimulation by the needles, duration of stimulation, etc.) vary from country to country and practitioner to practitioner. Overall, acupuncture is a relatively safe therapy, with a very low incidence of major adverse effects [16]. Despite the widespread use of acupuncture by patients with rheumatic diseases, there is skepticism about its true efficacy in controlling the symptoms and reducing the severity of arthritis. Multiple factors contribute to this skepticism. Arthritis can be of many different types, and therefore, correct diagnosis is essential to assess the final outcomes. Several clinical trials have been conducted on acupuncture in arthritis, but many of them suffer from the same drawbacks discussed above for clinical trials of herbal products [5,11,15]. Another confounding factor in acupuncture trials is the type of control groups used [15,17]. It is difficult to develop the ideal control: one that mimics acupuncture, but is physiologically inert. Sham acupuncture uses needles, which are either blunt or retractable, or may use puncture sites different from the standard acupuncture points. In many cases, these control procedures have been shown to relieve symptoms to some extent. This implies that sham acupuncture itself may have beneficial effects presumably attributable to altered physiological responses. Additional factors affecting the outcome of the acupuncture treatment are belief and expectation of the patient and the practitioner, therapeutic context, time and attention. There is no consensus yet on how to reconcile these factors with the beneficial placebo effect when assessing efficacy of acupuncture. The number of randomized controlled clinical trials of acupuncture in RA is rather limited compared to those in osteoarthritis (OA), the most prevalent form of arthritis. Of the two representative reported randomized controlled trials in RA, one showed a significant decrease in knee pain following electroacupuncture, whereas the other reported no significant benefit of acupuncture [5,18]. Both trials had several limitations. One of the most notable trials in OA was conducted at the Center for Integrative Medicine, University of Maryland, Baltimore, under the direction of one of us [19]. It was a randomized controlled trial involving 570 patients with OA of the knee. Patients received 23 true/sham acupuncture sessions over a period of 26 weeks. An additional control group received six 2-h education sessions in 12 weeks. The results clearly showed that acupuncture was an effective adjunctive treatment in controlling symptoms (pain) and improving function in the test group compared with the sham acupuncture and other control. This trial has laid a sound foundation for additional trials on OA and RA at other centers around the world, and the collective outcomes of such trials is going a long way in firmly establishing the scientific rationale for using acupuncture in the treatment of arthritis. In fact, the 2012 recommendations of the ACR include acupuncture as a treatment for OA [20]. Thanks Expert Rev. Clin. Immunol. 10(7), (2014)

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Traditional Chinese medicine

to the work of the Cochrane Collaboration Complementary Medicine Field, the National Center for Complementary Medicine at the National Institutes of Health, the Society of Acupuncture Research, as well as others, gaps in knowledge are being identified and recommendations have been published for the rigorous design and conduct of future TCM studies. One particularly encouraging area of focus is the emphasis on comparative effectiveness research that will allow us to bring together various stakeholders to design studies that will be true to the ‘real-world’ practice of TCM and help better inform clinical decisions [21]. Another component that is vital to the acceptance of both herbal therapy and acupuncture by conventional western medicine is rigorous basic and applied research into the mechanisms of action of these promising TCM modalities. Furthermore, herbal and other natural products and acupuncture have been shown to modulate immune responses [6,7,9]. Considering that RA is an autoimmune disease, inclusion of contemporary parameters of cellular and molecular aspects of immune responses as outcome measures should be considered in any clinical trial using TCM in RA patients. Similarly, application of advanced technologies (e.g., microarrays and proteomics) [22] to CAM research would offer additional evidence for the validity of

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Harris ED Jr. Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 1990;322(18): 1277-89 Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States. 2007;Natl Health Stat Report 2008 (12):1-23 Hartel U, Volger E. [Use and acceptance of classical natural and alternative medicine in Germany – findings of a representative population-based survey]. Forsch Komplementarmed klass Naturheilkd 2004; 11(6):327-34 Hunt KJ, Coelho HF, Wider B, et al. Complementary and alternative medicine use in England: results from a national survey. Int J Clin Pract 2010;64(11): 1496-502 Manheimer E, Wieland S, Kimbrough E, et al. Evidence from the Cochrane Collaboration for Traditional Chinese Medicine therapies. J Altern Complement Med 2009;15(9):1001-14 Goldrosen MH, Straus SE. Complementary and alternative medicine: assessing the evidence for immunological benefits. Nat Rev Immunol 2004;4(11):912-21 Cooper EL. The immune system and complementary and alternative medicine.

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CAM use in RA and other diseases. There is one aspect though that is not easy to bridge without investing a major effort at the grassroots of medical education, and that is the inherent difference in the philosophy of TCM versus western medicine. However, this gap can be closed by incorporating CAM at different levels of education and training of medical students and physicians. Such efforts are already underway at many centers throughout the world, including those associated with the Consortium of Academic Health Centers for Integrative Medicine and the Consortium for the Globalization of Chinese Medicine. The door is now open to broaden our understanding of healing traditions from other cultures and to potentially expand our toolbox for the evidence-based treatment of RA. Financial & competing interests disclosure

The authors were supported by grants from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM): R01 AT004321 (KD Moudgil) and P50 AT 00084 (BM Berman). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Evid Based Complement Alternat Med 2007;4(Suppl 1):5-8

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Traditional Chinese medicine: potential for clinical treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease affecting people worldwide. Increasing numbers of RA patients in the west are r...
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