Acupuncture and Knee Osteoarthritis

Context The evidence regarding acupuncture for treating osteoarthritis of the knee has been inconclusive. Contribution A total of 320 primary care practitioners and 1007 patients with osteoarthritis of the knee participated in this 26-week randomized trial. The proportion of patients achieving the primary end point (>36% improvement on a standardized measure of pain and function) was 53.1% for traditional Chinese acupuncture, 51.0% for sham acupuncture (blinded comparison), and 29.1% for medical treatment (nonblinded comparisons). Cautions All groups did not receive an appropriate placebo intervention. Implications Acupuncture (traditional or sham) was more effective than medical management alone. Needling alone, even in nontraditional insertion sites; more intensive medical attention; or placebo effects may be responsible for this result. The Editors Osteoarthritis of the knee is an important factor in health care cost in industrialized societies. In Germany, costs directly attributable to osteoarthritis were estimated to be approximately 5.4 billion Euro in 1995 (1, 2). Because there is no cure for osteoarthritis, most guidelines recommend a multimodal pharmacologic and nonpharmacologic approach until total knee replacement is indicated (3, 4). Pharmacologic treatment generally consists of nonsteroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors and nonopioid analgesics. Treatment is usually combined with patient education, social support, and physiotherapy. However, even this multimodal approach is often ineffective or has only short-term effects. The probability of adverse events increases with the duration of pharmacologic treatment. At the 1997 National Institutes of Health Consensus Conference on acupuncture (5), acupuncture was proposed as an option for reducing the dose of or avoiding the use of medication. However, the paucity of scientific evidence called for additional well-designed clinical trials. In a systematic review, 4 of 7 trials conducted in a total of 393 patients with knee osteoarthritis showed statistically significant effects of acupuncture compared with conservative therapy alone or sham acupuncture (6). However, most of the trials were poorly designed, none included long-term follow-up of more than 3 months, sample sizes were often too small, and there were relevant losses to follow-up or raters were not blinded. To determine whether to reimburse patients for the costs of acupuncture, German social health care insurance organizations initiated the German acupuncture clinical trials (www.gerac.de). An independent consortium of 4 German universities was invited to investigate the efficacy and safety of traditional Chinese acupuncture (TCA) versus sham acupuncture and standardized multimodal therapy for several indications, including osteoarthritis of the knee (7). The aim of our study was to compare long-term efficacy and safety (over 26 weeks) of standardized TCA; standardized minimal-depth acupuncture at nonacupuncture points (sham acupuncture) applied in addition to physiotherapy and as-needed anti-inflammatory drugs; and conservative therapy, including anti-inflammatory drugs and physiotherapy, for pain caused by osteoarthritis of the knee. We chose these treatments to investigate a general effect (if any) of the acupuncture needling procedures (acupunctures vs. conservative therapy) and a specific effect (if any) of the localization, stimulation, or depth of needling (TCA vs. sham acupuncture). Methods Participants A total of 1039 eligible patients were enrolled in the study between April 2002 and March 2004. The 320 physicians were selected from a group of experienced primary care practitioners participating in a large cohort study on acupuncture (www.gerac.de). The ethics committees of the University of Heidelberg and the University of Mannheim and all involved local ethics committees approved the study. The study protocol was consistent with the principles of the Declaration of Helsinki. The inclusion criteria were signed declaration of consent; age 40 years and older; chronic pain in the knee joint for the last 6 months, according to American College of Rheumatology (ACR) criteria (8); radiologic confirmation of osteoarthritis in 1 or both knees (KellgrenLawrence score 2 or 3 [9]); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (10, 11) score of at least 3 points; and a chronic pain score of at least 1, according to the criteria of von Korff and colleagues (12). Patients with other diseases affecting the knee, neurologic and psychiatric diseases, severe coagulopathy, pregnancy, or previous acupuncture treatment for osteoarthritis of the knee were excluded. A detailed list of eligibility criteria was reported by Streitberger and colleagues (13). The physicians checked the patients' eligibility criteria during a screening examination. A screening telephone interview was done to record baseline WOMAC values, quality of life (12-item Short-Form Health Survey [SF-12]) (14), von Korff scores (15), and use of analgesics. Finally, patients were randomly assigned into 3 treatment groups. Interventions Conservative therapy involved 10 visits to practitioners with consultation and a prescription for diclofenac, up to 150 mg/d, or rofecoxib, 25 mg/d, as needed until week 23. The protocol permitted 5 additional visits in weeks 7 to 13 if patients were graded as having a partially successful result (10% to 50% reduction in pain after 6 weeks based on the von Korff pain intensity scale) during a telephone interview. If a patient fulfilled the criterion for additional visits, the interviewer informed the patient during the interview and informed the related investigator by fax. The patient could choose whether to participate in the 5 additional visits. In the TCA and sham acupuncture groups, 10 acupuncture sessions administered over a 6-week period began 2 weeks after screening. Patients receiving acupuncture who met the criterion for partial success were also entitled to 5 additional treatment sessions. The defined TCA program followed recommendations for optimized acupuncture treatment in clinical studies (16). According to the traditional Chinese theory of the Bi syndrome to treat knee pain, the most important local acupuncture points were included as obligatory points ((1719). In addition, according to traditional Chinese diagnosis (including meridian theory and the most common syndrome differentiation of qi stagnation, kidney deficiency, and dampness and cold), 2 of 16 defined acupuncture points could be chosen. A maximum of 4 Ahshi points was also allowed (Table 1). Table 1. Components of Study Interventions as Defined in the Study Protocol Sham acupuncture was standardized as minimal-depth needling without stimulation at 10 points at defined distances from TCA points. One point was between the gallbladder and stomach meridian on the distal part of the fibula, 2 cun above the malleolus lateralis toward the knee (cun is a patient-related measure that is the width of a thumb, approximately 1.5 cm, and is used in TCM). Two points were 2 cun and 6 cun, respectively, above the malleolus medialis in the center of the tibia surface area, intracutaneous, without periosteum contact and in the direction of the knee. One point was in the center of the thigh on the connecting line from the center of the patella to the anterior superior iliac spine, in the direction of the hip. One point was on the highest spot of the tightened musculus biceps brachii. This control technique was chosen to minimize any supposed nonspecific antinociceptive physiologic effects of deep needling and strong stimulation, including the typical acupuncture sensation of deqi. Noninvasive sham devices, such as the placebo needle (20), were not used. The protocol prescribed the same general procedure, diagnostics, and communication with patients in the TCA and sham acupuncture groups. The same types of acupuncture needles were used for TCA and sham acupuncture, and all investigators were trained in both techniques. Both knees were treated if affected. When acupuncture did not reduce the pain to a level the patient found acceptable, patients could take up to 150 mg of diclofenac per day during the first 2 treatment weeks and up to a total of 1 g until week 23. Each of the 3 treatment groups had up to 6 physiotherapy sessions. Corticosteroids and other analgesics besides diclofenac and rofecoxib were explicitly excluded for all patients. Injections, infiltrations, moxibustion, cupping, and electroacupuncture were also prohibited. Additional details are shown in Table 1 and in the protocol published by Streitberger and colleagues (13). The patients knew whether they were in the conservative therapy group but were blinded to TCA versus sham acupuncture. The investigators were not blinded to treatment group, but the person doing the telephone interviews for end point measurement was blinded to treatment assignment. Randomization The 1:1:1 block randomization with block size of 6, stratified by center, was computer-generated by an independent statistician and was transferred to the randomization center. For each eligible patient, the practitioner called the randomization center and was immediately informed by fax of the patient's treatment group. Outcomes The effect on pain and function was measured with the WOMAC score (total score and the subscales standardized to 0 to 10). In patients with 2 affected knees, 1 knee was randomly chosen for evaluation during the initial telephone interview. According to the recommendations of the OsteoArthritis Research Society International ((21), success rates were calculated according to a change of at least 36% from baseline WOMAC scores at 13 and 26 weeks after the start of treatment (22). Patients with missing data were considered to have had treatment failure. Blinded central telephone interviews were conducted in weeks 13 and 26 to record the main an