| BackgroundRheumatoid arthritis is a systemic autoimmune disease with erosive arthritis as the main manifestation. It is likely to result in deformity and disability and has become one of the main causes for disability among the Chinese people, doing serious harm to human health. It is a symmetrical and persistent polyarthritis involving hands and small joints of the wrist. Its etiology and pathogenesis is unclear. Although in recent years the emergence of biological agents applied to the treatment of RA brought a landmark revolution, they are too expensive and their long-term efficacy and the possible side effects on human body still require large-scale follow-up study to accumulate more experience before actual application. Western medicine treatment of this disease aims mainly at controlling the deterioration of the disease, improving joint function and avoiding prognosis. In addition to general treatment and surgical treatment, the focus is mainly on drug treatment:biological agents, non-steroidal anti-inflammatory drugs, disease-modifying-anti-rheumatic drugs and glucocorticoids. Although these drugs can reduce symptoms and relieve pain, the overall efficacy is not satisfactory, and the side effects still need to be checked. TCM in the clinical treatment of this disease enjoys over2,000years of history. Rich experience has been accumulated and it is currently one of the common means of treatment of this disease. But because it is difficult to control the quality of traditional Chinese medicine, and also due to the lack of a rigorous multi-center sample of randomly controlled trial evidence to support the verification of its efficacy, plus most reports are about small sampling cases, safety matter needs to be further explored.ObjectiveThe author will try to give an objective evaluation on the overall efficacy and safety of treatment combining both western and Chinese medicine, so as to provide evidence-based support for the optimal solutions to the treatment of rheumatoid arthritis.MethodsSearch strategy:based on computer electronic databases and supplemented by manual searches. The keywords for search include "rheumatoid arthritis","rheumatoid arthritis","Bi Syndrome","Wang Bi","The Jiu-Bi","Lijie","rheumatoid arthritis"; subheadings in search include" Chinese medicine "," Integrative Therapy ’," Chinese medicine therapy and medical treatment combined with free-retrieval methods. English terms such as "rheumatoid arthritis "or" RA "," methotrexate "traditional therapy" or "substitution therapy" or "replacement therapy" or "plant*" or "Herb" are used as keywords and titles in search. The following electronic databases were retrieved:China Academic Journal (1979-2011.6)(CNKI)(including the database of Chinese Academy of Sciences, China Academic Journal century journals, full-text database of Chinese doctoral thesis, China Journal, China’s important conference papers full-text database, the full-text database of China’s major newspapers, China Yearbook Full-text Database), China Science and Technology Academic Journal database (1989-2011.6)(the Vip), Wanfang Database (1982-2011.6), Chinese Biomedical Literature CD-ROM database (1978-2011.6) (CBMDISC), China Biological Medicine journal database (CMCC), Chinese biomedical abstracts database network version (CBMWEB), the Chinese pharmaceutical literature data, MEDLINE/pubmed (1950-2011.6) on ScienceDirect, SpringerLink, and so on.The Inclusion criteria:(1) the type of research:randomly controlled trial. Randomly controlled trials refer to the use of the computer, random number tables, coin toss, dice, and draw lots to divide the patient group. Literatures were included in this systematic review as long as the author mentioned "patients were randomly divided into..."Blinded and unblinded studies were also included.(2) In terms of age, the literatures included in the study of clinical subjects shall be decided according to the experiment subjects. All objects included in the study are the default in line with the revised diagnostic criteria for rheumatoid arthritis in1987by the American College of Rheumatology.(3) Intervention measures:Interventions for the treatment group are western medicine and traditional Chinese medicine combined, including traditional Chinese medicine, Chinese patent drug, single herbs and Chinese medicine extent by extracts, all the prescriptions given by senior doctors and above. Interventions for the control group are western medicine alone, placebo or blank control.(4) Results:①total efficiency;②the improvement of all the clinical symptoms (joint pain index, index of joint tenderness, joint swelling index, duration of morning stiffness, hands’average grip strength,20m walking distance); secondary outcome measures:safety indicators; the improvement of laboratory parameters (including erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein).The Exclusion criteria:(1) re-published literature;②Literature reviews;③unknown literature data.Data collection:this systematic review literature search was performed independently by two reviewers (Li Ruichang and Feng Zhitao), first from the title and abstract, and when the title and abstract judgment cannot render further identification, the whole literature will be checked through. Inclusion and exclusion of literatures shall be in strict accordance with the above-mentioned criteria, and if there are disagreements between the two reviewers, a third person (also trained professional) Wang Jiguo will step in to judge the article. If the literature included doesn’t mention the random method, then the reviewers will try to contact the author to confirm whether the random method was adopted in the literature. The two evaluators in accordance with the literature information extraction table independent of the included studies will input information independently. After verified by a third party, a backup is retained for analysis of data.Quality assessment of literatures:two literature reviewers trained in clinical epidemiology will use a modified Jadad scale score with RCTs1-7points (1-3divided into low-quality studies4-7is divided into high-quality research) to evaluate.Statistic analysis:statistical analysis will use the ReviewManage5.0software provided by and downloaded from Cochrane Collaboration website. Meta-analysis of the data includes dichotomous data, continuous data, and ordinal data. For dichotomous data, the analysis of heterogeneity shall firstly be conducted. If the study doesn’t show heterogeneity, then P>0.05fixed model will be adopted; otherwise, stochastic model analysis will be used. The literature publication discrimination will be analyzed through a funnel plot. Data counting relies on the relative risk (RR) and95%confidence interval (CI) measurement; quantifying data uses the weights of the mean difference (WMD) and95%confidence interval (CI). Subgroup will be analyzed according to the possible heterogeneity factors. When clinical heterogeneity doesn’t exist, and when there is significant heterogeneity between the tests, a random effect model will be applied; otherwise, fixed effects model is the choice. Heterogeneity test level is set to P≥0.1; if the clinical heterogeneity between studies within the subgroup exists, no merger analysis of data will be carried out. The potential bias of literatures will be shown by the funnel plot.Results1. A total of1098literatures were searched, and finally65randomly controlled studies of traditional Chinese medicine combined with Western intervention in rheumatoid arthritis treatment were included. An overall low quality clinical research, with no more than3points was obtained.2. The65literatures included in the research are divided into three groups according to intervention measures.9Integrative treatments of RA researches take traditional Chinese medicine as a integrated independent treatment, overall efficacy trends obtained by Meta:nine of the heterogeneity test card square=18.95, df=8(P=0.02), I2=58%, using a random effects model.A total of769patients with RA were examined. The value of the combined OR and95%confidence interval [CI] was0.36[0.19.0.69], the total efficiency of the Z value=3.09(P=0.002).6of the95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting that combination therapy group and the control group with western medicine alone show no efficacy difference, and another three studies95%confidence interval horizontal line falls on the left of effective vertical bar, the results, suggesting that Integrative Medicine treatment group enjoys advantages in overall efficacy than western medicine alone.95%confidence interval dash on the right side, suggesting no support for better efficacy of western medicine alone than that of Integrative Medicine.There are six test applications intended party+MTX single compared with MTX. This article explores the efficacy of traditional Chinese medicine, traditional Chinese medicine as a whole, a stand-alone interventions application of meta analysis and evaluation of the overall efficacy trends:6of the test for heterogeneity chi-square value of7.02, df=5(P=0.22) I2=29%, using a fixed effects model. A total of415patients with RA, the value of the combined OR and95%confidence interval [CI]0.59[0.34,1.02], the total efficiency of the Z value=1.89(P=0.06). Which5of the95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting that combination therapy group and western medicine alone control group efficacy there is no difference, otherwise one study95%confidence interval, horizontal fall effective vertical bar on the left, the results suggest that Integrative Medicine treatment group, RA there is always more efficient than western medicine alone.95%confidence interval dash on the right side of the study, ie, did not support the efficacy of western medicine alone is better than the study of Integrative Medicine.4test is intended party/proprietary Chinese medicines+MTX compared with MTX single agent. The following discussion of the five clinical trials of total efficiency. In order to find the trend of the efficacy of traditional Chinese medicine as a whole:four of the test for heterogeneity chi-square=3.84, df=3(P=0.28) I’22%, using fixed effect model. A total of265patients with RA, the value of the combined OR and95%confidence interval [CI]0.37[0.17,0.78], the total efficiency of the Z value=2.62(P=0.009). Which three of the95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting that combination therapy group and western medicine alone control group efficacy there is no difference, otherwise one study95%confidence interval, horizontal fall effective vertical bar on the left, the results suggest that Integrative Medicine treatment group, RA there is always more efficient than western medicine alone.95%confidence interval dash on the right side of the study, ie, did not support the efficacy of western medicine alone is better than the study of Integrative Medicine.There are two pilot treatment programs are self-intended side+MTX+of SASP+celecoxib compared with MTX+of SASP+celecoxib treatment program serves the same purpose. Included in the two studies test for heterogeneity chi-square value of0.20, df=1(p=0.66) I2=0%, the fixed effects model. A total of230patients with RA, the value of the combined OR and95%confidence interval [CI]0.35[0.16,0.77], the total efficiency of the Z value=2.61(P=0.009). Which one study95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting that combination therapy group and western medicine alone control group efficacy there is no difference, otherwise one study95%confidence interval, horizontal fall effective vertical bar on the left, the results suggest that Integrative Medicine treatment group, RA there is always more efficient than western medicine alone.95%confidence interval dash on the right side of the study, ie, did not support the efficacy of western medicine alone is better than the study of Integrative Medicine.There are two pilot treatment programs are self side+MTX+of SASP+meloxicam with MTX+of SASP+merlot meloxicam contrast, treatment options serves the same purpose. Included in the two studies test for heterogeneity chi-square value of1.25, df=1(p=0.26) I2=20%, using a fixed effects model. A total of163patients with RA, the value of the combined OR and95%confidence interval [CI]0.30[0.12,0.78], the total efficiency of the Z value=2.50(P=0.01). Which one study95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting that combination therapy group and western medicine alone control group efficacy there is no difference, otherwise one study95%confidence interval, horizontal fall effective vertical bar on the left, the results suggest that Integrative Medicine treatment group, RA there is always more efficient than western medicine alone.95%confidence interval dash on the right side of the study, ie, did not support the efficacy of western medicine alone is better than the study of Integrative Medicine.3. Improvement of symptoms and laboratory parameters:a subgroup analysis from the time of morning stiffness, joint tenderness index, joint swelling index, dual-grip strength, ESR, CRP and RF aspects of each clinical trial data: most of the research suggests that Integrative Medicine in improving symptoms and laboratory parameters, there is no difference compared with western medicine alone group, a small part of the Integrative Medicine western medicine alone in improving the symptoms and laboratory parameters because research suggests. The combined effect size and diamond-shaped diagram fall on the left side of the equivalent line prompt on the whole. Western medicine combined with the treatment of RA is better than western medicine alone in improving symptoms and laboratory parameters.4.Security indicators:adverse reactions occur:Included in the study of the test for heterogeneity chi-square value=6.11, I2=18%, using fixed effect model. A total of565patients with RA, the combined OR values and95%confidence interval [CI]0.23[0.14,0.39], the total efficiency of the Z value=5.47(P<0.00001). The diamond-shaped box after the merger falls equivalent vertical bar on the left, prompted Chinese and Western medicine combined with the security of the treatment group, the treatment of RA is better than western medicine alone. Which three of the95%confidence interval of vertical and horizontal equivalent vertical lines intersect, prompted the safety of the treatment group and the comparison group, Integrative there is no difference, while four studies95%confidence interval horizontal drop Integrative Medicine in the equivalent vertical bar on the left, the results suggest that the security of the treatment group, the treatment of RA is better than western medicine alone.95%confidence interval dash on the right side of the study, that does not support the simple western medicine treatment of security is better than in Integrative Medicine Research.Included in the two studies, the test for heterogeneity chi-square=0.10, df=1(P=0.75) I2=0%, using a fixed effect model. A total of168patients with RA, the value of the combined OR and95%confidence interval [CI]0.38[0.15,0.92], the total efficiency of the Z value=2.13(P=0.03). Two of the95%confidence interval of vertical and horizontal equivalent vertical lines intersect, suggesting Integrative treatment group and the comparison group, no statistical difference in adverse reactions.Conclusion1.The studies included in this research are of comparatively low quality, and the standards for efficacy judgment varied. The distribution of the primary outcome measures and secondary indicators is uneven. Studies included in research with similar research purposes and consistent program of clinical studies were analyzed, the result of which demonstrated that Integrative treatment of RA showed better overall efficacy than western medicine alone. From each sub-group analysis, the combined total amount of the effect of diamond-shaped diagram falls equivalent on the left side of the vertical line of Integrative Medicine, suggesting that the overall efficacy trends in treating RA is better than western medicine alone. Diamond-shaped diagram of the combined effect size falls on the left side, which suggests that integrative treatment of RA showed better effects in improving symptoms and in terms of laboratory parameters than western medicine alone.2. Integrative treatment of RA was better in terms of safety than western medicine alone. The combined diamond diagram and the effect amount indicate that Integrative treatment of RA can generate higher safety than western medicine alone.3. The evaluation provides evidence-based support for the treatment of RA with Integrative methods and provides a reference for more systematic and scientific clinical research of traditional Chinese medicine. The low quality of literatures included in the review as well as the problems exposed in these literatures teach a lesson and offers reference for future optimal design. Follow-up high-quality research and systematic reviews still need rigorous design, and scientific large sampling of multi-center study.Evaluation of this system shows deficiencies in the quality of literatures. Thus the system itself has some limitations and the conclusion gained is persuasive only within a certain range. A number of journals of clinical reports urgently need to uniform their format in order to provide more high quality original statistic evidence, and ultimately push forward a better and faster development in future clinical research on traditional Chinese medicine. |
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