Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study

In recent years, patients with chronic rheumatic disorders are adopting complementary/alternative medicine (CAM) to help manage their chronic painful conditions. In previous reported arthritic studies, the prevalence of CAM was between the range of 33–90% [1]. Collectively the evidence demonstrates that some CAM modalities show significant promise such as acupuncture, diets, herbal medicine, homoeopathy, massage and supplements. Of these modalities, acupuncture has been shown to be effective for a number of painful conditions including chronic knee [2] and neck pain [3]. It is defined as the stimulation of a certain point or points on the body, by the insertion of needles, to achieve a desirable effect. It is thought to prevent or modify the perception of pain or to alter physiologic functions, including pain control for the treatment of certain diseases or dysfunctions of the body [4]. Acupuncture typically includes manual stimulation of needles, but there are variations commonly used, such as electrical stimulation and heat stimulation of needles, which is called moxibustion: the moxa herb, Artemisia vulgaris, is burned at the handle end of the needle. Injection acupuncture, in which herbal extracts are injected into acupuncture points, are occasionally used as well [5]. It is unclear which type of acupuncture produces the most beneficial effect [6].

Recent randomized trials and meta-analysis in patients with osteoarthritis of the knee, acupuncture has been shown to provide pain relief and improvement in joint function [7‐9]. In contrast, evidence for this form of treatment in inflammatory joint diseases is sparse and is inconclusive [10, 11]. The effect of traditional Chinese acupuncture (TCA) or electroacupuncture (EA) on the objective and subjective measures of disease activity in patients with RA was reviewed recently [12]. There were only 2 studies which were suited for analysis. In one cross-over study, acupuncture was considered ineffective [11]. Questions were raised in the methodology including the choice of the acupuncture point, the treatment duration and frequency [13]. The second study compared electro-acupuncture to sham acupuncture. Problems with this study include the purpose for the use hydrocortisone injection which may have impacted on the results. Other concerns were the outcome measures used as well as the methodology of reporting the results [12].

In planning a randomized controlled trial of acupuncture, we conducted a pilot study using validated outcome measures to explore the feasibility of the protocol and obtain preliminary data on efficacy and tolerability of 3 different forms of acupuncture treatment as an adjunct for the treatment of chronic pain in patients with RA. We wished to address the questions of a) the accrual and dropout rates, b) compliance with the protocol, c) adverse event. We also wished to explore d) the feasibility of the planned standardized outcome measures, and e) the variability in the primary clinical outcome measure. We chose these treatments to investigate a specific effect (if any) of the stimulation, or depth of needling (TCA or EA vs. sham acupuncture).

This pilot study found that about half of the RA patients with persistent active disease despite DMARDs were willing to try acupuncture as an adjunct for pain relief. The accrual rate was reasonable since this is only a single center study. Dropout rate was low for both electroacupuncture (0%) and traditional acupuncture (16.7%). However, the dropout rate for Sham acupuncture was rather high (25% at week 10, 41.7% at week 20). Adverse events were minimal.

This is the first reported randomized, controlled trial on the efficacy and tolerability of traditional Chinese acupuncture compared with electro-acupuncture and sham acupuncture in patients with refractory RA using multiple local and distal points. Although the pain scores did not differ between the 3 groups, this study shows that both traditional acupuncture and electro-acupuncture may serve as an adjunct by reducing the number of tender joints in patients with refractory RA compared to sham acupuncture. Previous studies published about the efficacy of acupuncture are difficult to interpret due to methodological problems [12]. The important point of our study is that it is a study in the methodology of acupuncture research as discussed in the following paragraphs.

Previous studies used different definitions for sham acupuncture, including insertion of needles adjacent to traditional point without manipulation [19], points with no known effects [10], points far away from the painful area without stimulation [20], distant arbitrary points [21], superficial insertion of needles into non-classical points [22], and real acupuncture point but no skin puncture [11]. However, some of these acupuncture points that were used may still be effective [21]. The retractable type of sham needle [23, 24] has been intended for use in acupuncture-naïve subjects or subjects with limited acupuncture experience. However, in a Japanese study [25], 60% of the subjects could distinguish between sham and genuine needling, probably due to the fact that most people in Asian countries have more knowledge and experience with acupuncture. Our group found that sham sites and superficial punctures lead to inadequate blinding since more than 50–85% of recipients could immediately recognize that they are not receiving real acupuncture. The special device we used which hide the distal end of the needle was effective as 85% patients who received acupuncture in the hand and 90% patients who received acupuncture in the leg were unable to distinguish whether they were receiving real or sham acupuncture [15]. There was no significant difference between those who had received previous acupuncture or not [15]. In this study, there is no significant treatment effect demonstrated in the sham acupuncture group as all the outcome measures remained unchanged except the patient's global score. Moreover, significantly more patients from the sham acupuncture group dropped out prematurely due to inefficacy compared to the 2 acupuncture groups.

We chose these treatments to investigate a specific effect of the stimulation, or depth of needling (TCA or EA vs. sham acupuncture). We acknowledge the fact that waiting list controls may be useful to ascertain the extent of placebo effects of the acupuncture setting (for example, contact factors, talking and listening, and credibility of the intervention), patient preferences and expectation. Indeed, the fact that both the acupuncture and sham groups reported significant improvements in the patient's global score and a trend towards a reduction in the pain score suggests that acupuncture may elicit a greater placebo effect. However, the dropout rate for patients randomized to waiting list controls may be even higher than Sham acupuncture due to pre-randomization preferences for acupuncture. By having to wait for a treatment that they believe is effective, patients may also be disappointed by the delay, which may influence their ratings of subjective outcomes while waiting.

There have been 9 studies which examined the efficacy of acupuncture in RA [11, 26]. Our study differs from others as 6 acupuncture points were used including local and distal points. Literature suggested that a combination of at least 4 distal and local points are required for treating systemic inflammatory diseases such as RA [27]. We have chosen the 6 acupuncture points since all of them can be regarded as distal points for the treatment of the underlying systemic inflammatory disease, as well as local points treating the arthritis of the nearby joints including the elbows, hands, wrists, knees and ankles based on the widely accepted Traditional Chinese Medicine theory of 'Bi' syndrome [17].

The acupuncture technique was questionable in previous studies as the duration of treatment were variable and the sensation of "de Qi" was not mentioned [10, 11]. David et al employed only one single point selected for a short duration of 4 minutes in situ and manipulated at 2 minutes for 5 seconds [11], while Man and Baragar used electrostimulation of 3 well known classical points for 15 minutes [10]. Camerlian et al defined acupuncture as 20 minutes of electrostimulation of major classical points with "de Qi" [22]. According to both traditional Chinese and Western acupuncture theory, good results can be achieved when needles are left inserted for 15–30 minutes [13]. Therefore, we believed that a 40 minute – session with "de Qi" should be adequate for the proper treatment of our patients.

The lack of improvement in the pain score was disappointing. In general, analgesia is obtained by short-term acupuncture, whereas curative acupuncture requires long-term acupuncture treatment procedures. In the Man study, patients only received one single session of acupuncture [10] whereas in the David study, patients only received 5 weekly sessions. In standard practice, acupuncture treatment twice a week for at least 5 weeks may be required in chronic painful conditions like RA [13]. Hence, our study was carefully designed so that patients can receive 2 weekly sessions over a period of 10 weeks. We believed that this duration of treatment should be adequate in achieving positive results should there be any. However, since these patients are having advance disease, whether patients with earlier, more potentially reversible/treatable disease may benefit remains uncertain.

This is the first randomized study that demonstrated a reduction of the number of tender joints in patients with refractory RA after acupuncture, although the effect wears off soon after stopping acupuncture treatment. This study does not suggest any additional advantages of electroacupuncture over the traditional acupuncture. Electrical acupuncture might work best in situations that involved significant muscle spasm. Bhatt-Sanders has identified 5 positive studies which suggested acupuncture treatments give significant pain relief, 2 studies which showed no significant differences between real and placebo acupuncture [26]. However, these studies did not use the recognized outcome measures such as the ACR core components and the methodologies were problematic. Recent review has identified only 2 randomized controlled trials that provided the best evidence there is today. In the Man and Baragar study [10], a significant decrease in knee pain was reported with electroacupuncture at 24 hours, and 4 months post treatment. The outcome measure used is not currently recognized and the quality of the data was impacted by poor reporting and the use of hydrocortisone injection in the contralateral knee [12]. In the David study [11], acupuncture was shown not to be effective for those with symptoms of RA. The methodology was well described but the acupuncture technique was questionable. These studies illustrate the inherent difficulties related to acupuncture trials which included the design of the study, definition of acupuncture itself and elimination of bias as discussed before. Future study may consider incorporating the tender joint count as one of the main outcome assessment.

Five previous studies had examined acupuncture for potential anti-inflammatory effects [10, 11, 22, 28], only one showed an anti-inflammatory effects with decreased rheumatoid factor, IgA, IgG levels, and decreased T cell activity with no change in ESR [29]. Our findings concurred with majority of the previous studies that no significant anti-inflammatory effect was observed in terms of changes in the DAS score, the number of patients achieving ACR20, ESR, CRP levels or other clinical parameters except a modest reduction of the number of swollen joints only in the group who received traditional Chinese acupuncture. Recent data suggests that acupuncture may have anti-inflammatory action via release of neuropeptides e.g. calcitonine gene-related peptide from nerve endings [30]. Whether this is also true in RA would need to be addressed in future trials as one of the secondary outcomes.

This is a study of the methodology of acupuncture research and thus confined by a clear-cut regimen. This is very different from the usual traditional Chinese acupuncture practiced which is characterized by a holistic approach to the management of the disease. Therefore, the practitioner of traditional acupuncture will approach each patient with a personalized treatment plan rather than treating all patients with RA using a standard protocol. In practice, practitioners tend to use certain patterns of points on all of most of their patients [31]. Our treatment protocol was specially designed to reflect the best practice based on the widely accepted Traditional Chinese Medicine theory of 'Bi' syndrome as this could be replicable.

Our preliminary evidence suggests that electroacupuncture and traditional acupuncture were no better than sham acupuncture in terms of changes in the pain score. Acupuncture is safe and may be effective as an adjunct in reducing the number of tender joints, although no clear anti-inflammatory effects had been demonstrated. Further preliminary studies may consider including both pain score and tender joint count as the main outcome assessment. This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for RA.