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Tripterygium Glycosides for Treating Late-onset
Rheumatoid Arthritis: A Systematic Review and
Xiao Xu, MS; Jinquan Li, PhD; Sha Xia, MS; MiaoMiao Wang, MS; Wei Ji, PhD
Context • Older- or late-onset rheumatoid arthritis
(LORA) is defined as rheumatoid arthritis (RA) with an
onset of symptoms at age 60 y or older, which includes a
specific clinical course and features. To date, a specific
therapeutic treatment for LORA is still a dilemma in
Objective • The study aimed to assess the effectiveness
and safety of Tripterygium glycosides for treating LORA.
Design • Seven databases were searched from their
inceptions until June 2015. The research team included
randomized, controlled trials (RCTs) in which
Tripterygium glycosides were employed, either alone or as
an adjuvant treatment with disease-modifying
antirheumatic drugs (DMARDs), in patients with LORA.
The selection of studies, data extraction, and validation
were performed independently by 2 reviewers. The
Cochrane risk-of-bias criteria were used for evaluating the
quality of the included studies.
Settings • The study was conducted at Changzhou
University (Changzhou, China), Nanjing University of
Chinese Medicine (Nanjing, China), and the hospital
affiliated with Nanjing University of Chinese Medicine
Participants • Studies including patients aged 60 y or
older with RA in any of their peripheral joints were
included in the meta-analysis.
Intervention • All participants in the included studies
were administered Tripterygium glycosides, either alone
or together with other DMARDs, for at least 3 mo.
Xiao Xu, MS, is Teaching Assistant in the School of
Pharmaceutical and Life Science, School of Nursing,
Changzhou University, in Changzhou, China. Jinquan Li,
PhD, is attending in the Department of Orthopedics,
Fuzhou General Hospital of Nanjing Military Command,
People’s Liberation Army (PLA), in FuZhou, China. Sha
Xia, MS; and MiaoMiao Wang, MS; are residents, Wei Ji, PhD,
is a professor in the Department of Rheumatism, Affiliated
32 ALTERNATIVE THERAPIES, NOV/DEC 2016 VOL. 22 NO. 6
Outcome Measures • The primary outcomes included
(1) the swollen joint count (SJC) and (2) the tender joint
count (TJC). The secondary outcomes included the
erythrocyte sedimentation rate (ESR) and the level of
C-reactive protein (CRP).
Results • Four RCTs met the inclusion criteria, and most of
them were of low methodological quality. The results of the
current meta-analysis indicated that Tripterygium glycosides
plus DMARD therapy, when compared with DMARD
therapy alone, showed a favorable effect: (1) on the SJC, with
the mean difference (MD) = -1.58, 95% confidence interval
(CI) = -1.64 to -1.51, and P < .01; (2) on the TJC, with the
MD = -1.71, 95% CI = -2.26 to -1.15, and P < .01; (3) on the
CRP levels, with the MD = -9.96, 95% CI = -10.96 to -8.96,
and P < .01; and (4) on the ESR, with MD = -10.74, 95%
CI = -12.47 to -9.00, and P < .01. In addition, the groups
treated with Tripterygium glycosides were not superior to the
intervention groups that did not use Tripterygium glycosides
in terms of decreasing adverse events.
Conclusions • A lack of sufficient trials contributed to the
small sample size of the combined, eligible RCTs, and it
was difficult to draw firm conclusions on the positive
effects of Tripterygium glycosides and on their efficacy as
an effective intervention for treating RA. A high risk of
bias existed among the available RCTs. Further work with
more RCTs on a larger patient population is necessary to
confirm the efficacy and safety of Tripterygium glycosides
for treating LORA. (Altern Ther Health Med. 2016;22(6):3239.)
Hospital of Nanjing University of Chinese Medicine, in
Corresponding author: Wei Ji, PhD
E-mail address: email@example.com
Xu—TG for Treating LORA
and a more likely involvement of the proximal joint.35 However. the current research team has carried out a systematic review with an aim to summarize and critically evaluate the evidence from clinical trials that have tested the benefits and harms of Tripterygium glycosides for the treatment of LORA. Studies were excluded if (1) the control-group treatments were not relevant to the DMARD therapy. (2) disease-modifying antirheumatic drugs (DMARDs). the prevalence of LORA has been estimated at approximately 2% in the United States.14 Currently. The search included terms such as rheumatoid arthritis. at least 3 controlled.com.com O lder. no systematic review of past trials has targeted populations of older adults. geriatric. To subscribe. To share or copy this article. (2) other traditional Chinese therapies (eg. the Chinese BioMedical Database.13. approximately US$10 per month. the protocol of the current systematic review was registered in PROSPERO. the Chinese WeiPu Database. especially RA. or other forms of Chinese herbal medicine were administered. and chronic kidney disease. and the Cochrane Central Register of Controlled Trials as well as 4 Chinese databases—the WanFang Med Database. systemic lupus erythematosus. as well as a poorer quality-of-life index.32 In addition.34. visit alternative-therapies.28. acupuncture. a more frequent acute onset.5-8 However.3. a specific therapeutic treatment for LORA is still a dilemma in modern medicine. old-age. early hot-water decoctions had produced unfavorable toxicity profiles. NOV/DEC 2016 VOL. Novel biological therapies have been shown to have impressive results but may be too expensive for clients in developing countries. a longer duration for morning stiffness.4 Compared with young-onset rheumatoid arthritis (YORA). double-blind studies in China and North America had demonstrated that the Tripterygium glycosides.33 Previously. and aged.23-30 In China. (2) used Tripterygium glycosides as the sole intervention or as an adjunct therapy in conjunction with DMARDs for LORA.9-12 Although countless efforts have been made. especially in patients with a negative rheumatoid factor (RF). DMARD therapy is unsuccessful at times or achieves partial success. like for YORA patients.33 Therefore. 22 NO.1-3 Recently. no specific guidelines exist as of yet for treating LORA. and (5) to improve the quality of life. Use ISSN#1078-6791. Chinese herbals. Data Sources. (4) to decrease excess mortality. The overall management of LORA follows the guidelines for YORA: (1) to control the clinical manifestations. such as decoctions and formula. LORA can exhibit different clinical courses and features. (3) corticosteroids. and (3) included a placebo and DMARDs as controls (ie. Trials published in the form of dissertations were also selected as eligible studies.This article is protected by copyright.or late-onset rheumatoid arthritis (LORA) is defined as rheumatoid arthritis (RA) with an onset of symptoms at age 60 years or older.31. that patented Chinese medicine has been widely applied by rheumatologists as a standard therapy for RA in Chinese hospitals and has been accepted by patients due to a low cost of treatment. thundergod vine.6. 6 33 . hundreds of thousands of patients with RA have been successfully treated with TwHF. All studies included met the following inclusion criteria: (1) included patients aged 60 years and older with RA in any peripheral joint(s).33. (2) to decrease the pain and inflammation. is a member of the Celastraceae family of perennial. Tripterygium glycosides. Tripterygium. LORA composes 10% to 33% of all RA cases. MEDLINE. Tripterygium wilfordii extract.8 Recently. have been authorized for use since the 1970s as a Chinese patent medicine by the China State Food and Drug Administration. clinical trials (RCTs) related to the effects of Tripterygium glycosides in LORA were included in the current systematic review. funded by the UK National Institute for Health Research (registration No.21. ankylosing spondylitis. and (4) the study did not include the primary outcomes—the swollen joint count (SJC) and the tender joint count (TJC)— and the secondary outcomes—the erythrocyte sedimentation rate (ESR) and the levels of C-reactive protein (CRP). please visit copyright. Tripterygium glycosides may be a promising and suitable alternative therapy for treating LORA patients. Therefore. (3) other preparations of TwHF. It has been widely used in the treatment of a wide spectrum of autoimmune and inflammatory diseases. could be as effective as synthetic DMARDs in the treatment of YORA. different studies report conflicting results in the prognosis for LORA. Procedures The current study was conducted following the guidelines in Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).37 In addition.15-20 However. recent research has suggested that Xu—TG for Treating LORA Tripterygium glycosides should be used in postmenopausal female patients and in patients who have lower fertility requirements. Embase. The following databases were searched from their inception until June 2015: PubMed. and the China National Knowledge Infrastructure. although many studies have explored the issue. CRD42015025012). as a kind of herbal DMARD. elder. Leigong Teng ALTERNATIVE THERAPIES. (3) to preserve the damaged joint. to get a more-favorable safety profile. Previous systematic reviews and meta-analyses36 have been carried out to examine the effectiveness and safety of Tripterygium glycosides for a young population. in the field of modern medicine 4 main classes of drugs are used in the treatment of LORA: (1) nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore. METHODS Selection of Studies Only the randomized.22 Tripterygium wilfordii Hook F (TwHF). the bioactive constituents from TwHF. commonly known as Lei Gong Teng in traditional Chinese medicine.28 However. However. or Chinese patent medicines) were used as an adjunct treatment in conjunction with the DMARD therapy. DMARD therapy was used as a reference standard therapy for LORA in the control group). vine-like plants. and (4) biological agents. including lower rates in females.
unclear. the random-effects model was used if articles were considered to be similar enough clinically. (3) the therapy used by the intervention groups (ie. To share or copy this article. 6 4 studies included in qualitative synthesis 4 studies included in quantitative synthesis (meta-analysis) Abbreviations: TwHF. The duration of the interventions in the Figure 1. a third reviewer from the research team was consulted before the reviewers made the final decision on the disagreements. leaving 4 eligible RCTs involving 248 participants for the systematic review (Figure 1). and high risk of bias. Statistical Analysis The meta-analysis was performed using the software RevMan 5. (4) attrition bias. Other traditional Chinese therapies in the control group (n = 6) 4. (3) detection bias. the team also identified relevant studies via a review of the databases of Chinese Clinical Trial. The dosage of Tripterygium glycosides ranged from 30 mg to 60 mg per day. and high referred to a low. and Validation. the χ2 and I2 tests were used to assess statistical heterogeneity. The complete text of each included article was read by 2 independent reviewers from the research team. Use ISSN#1078-6791. Outcomes (n = 3) Intervention To be included. available from Cochrane’s Web site for free. The following data were extracted from the original manuscripts: (1) author and year.com or Lei Gong Teng. In most cases.gov. placebo. All RCTs originated in China and had a relatively small sample size. Tripterygium wilfordii Hook F. triptolide. and duration of treatment). Registry ClinicalTrials. the studies in the current meta-analysis must have required participants to take the Tripterygium glycosides alone or with other DMARDs for a period of at least 3 months. disagreements were resolved by discussion between the 2 reviewers. UK). The Cochrane risk-of-bias tool was used to evaluate the methodological quality of each included trial. visit alternative-therapies. the research team attempted to assess publication bias using a funnel plot. and duration of treatment).39 When a sufficient number of studies were available (ie. a fixed-effects model was applied. and CRP. and (6) adverse events. type of DMARD.38 Given an I2 < 50% and a P > . Xu—TG for Treating LORA . methods of administration. If the disagreement remained after discussion. the mean difference (MD) was included in the meta-analysis.This article is protected by copyright. ESR. with 95% confidence intervals (CIs). controlled clinical trial. 23 were excluded because they did not satisfy the inclusion criteria. and (5) reporting bias. Furthermore. respectively. Of those 27 articles. (5) outcomes for the SJC.44 All trials compared a cointervention of Tripterygium glycosides and DMARDs. the research team analyzed 27 fulltext articles. NOV/DEC 2016 VOL. disease-modifying antirheumatic drugs. such as a tablet. TJC. with a control of DMARDs alone. (2) performance bias. to identify grey literature or unpublished studies. The control group treatments were not relevant to the DMARDs therapy (n = 6) 3. Three41-43 used diagnosis criteria from the ACR 1987. Flowchart of the Trial Selection Process 120 studies identified through database searching 0 studies records identified through other sources 120 studies 10 duplicate studies excluded 110 studies screened 83 studies excluded 27 studies assessed for eligibility 23 studies excluded 1. randomized controlled trial. the research team presented the results as a risk ratio (RR). Quality. and one used criteria from the ACR/EULAR 2009. Data Extraction. (2) diagnostic criteria and sample size. at least 10 studies). uncertain. method of administration. DMARD. Pharmaceutical companies marketing Tripterygium glycoside products were requested to provide relevant published and unpublished data. dose. For continuous data. In each meta-analysis.38 For dichotomous data. the research team also searched the reference lists of reviewed articles and identified RCTs for any possible titles matching the inclusion criteria.com. The search terms were slightly modified for each database. dose. The terms low.38 and each RCT was assessed for the following characteristics: (1) selection bias.40 34 ALTERNATIVE THERAPIES. On the other hand. RESULTS Meta-analysis: Flow and Characteristics The search of databases generated 120 citations. To subscribe. and the Food and Drug Administration Web site.1. please visit copyright. After excluding the duplicate manuscripts and titles and those that met the exclusion criteria. the form of the Tripterygium. 22 NO. and clinical trials. Other preparation of TwHF were administered in the intervention group (n = 8) 2. In addition. Oxford.2 (Cochrane Collaboration. (4) the therapy used by the control groups (ie. who extracted relevant data based on predetermined criteria.
3 ×/d—plus (B) ACR 1987 60 6 mo n = 30. visit alternative-therapies. NOV/DEC 2016 VOL. SJC. Risk-of-Bias Summary 50% 75% 100% High risk of bias Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personelle (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias included trials was 6 months. The sources of funding were described in 3 trials. MTX. (B) DMARDs—MTX—7. please visit copyright. C-reactive protein. (A) Tripterygium glycosides tablet—20 mg. CRP. Long41 (2014) + + - + - + + Sheng42 (2002) + + - + + + + Yang43 (2013) + - - ? + + + Zhang44 (2011) - - - ? + + + + Low risk of bias ? Unclear risk of bias . (A) Tripterygium glycosides tablet—10 mg. 6 35 . To subscribe. SJC. The Characteristics of the 4 Included Trials Study Diagnostic (Author/Year) Criteria ACR 1987 Long et al41 (2014) Control Group (B) Regimen n = 24.44 Of the 4 included RCTs. NSAIDs were used according to patients’ conditions n = 30. ESR. 1/d Sheng et al42 (2002) n = 30. Risk of Bias Summary: Review Authors’ Judgments About Each Risk of Bias for the Included Studies Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personelle (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias 0% Low risk of bias Unclear risk of bias Figure 2. (A) Tripterygium 2009 glycosides tablet—10 mg. SJC. TJC. disease-modifying antirheumatic drugs. tender joint count. ESR.44 The sources of direct funding were medical university or governmental research foundations. Considering other biases. ESR. NSAIDs. leflunomide.5 mg. 3 RCTs42-44 stated the risk of bias for dropouts or withdrawals of participants. 3 ×/d—plus (B) ACR/EULAR 80 6 mo n = 40. NSAIDs were used according to patients’ conditions Yang et al43 (2013) Zhang et al44 (2011) Sample Intervention Group (A) Size Follow-Up Regimen 48 6 mo n = 24. SJC. nonsteroidal anti-inflammatory drugs. whereas the assessor blinding was unclear in 2 RCTs. (B) DMARDs—LEF. 3 ×/d—plus (B) ACR 1987 60 6 mo n = 30. swollen joint count. To share or copy this article. European League Against Rheumatism. NSAIDs were used according to patients’ conditions n = 40. therefore. whereas the remaining trial39 did not describe the methods of sequence generation. DMARDs.42.com. LEF. (B) DMARDs— MTX—10 mg. TJC. 20 mg. TJC. (A) Tripterygium glycosides tablet—20 mg. Three of the included trials36-38 reported appropriate sequence-generation methods for the randomization. 22 NO. TJC.43. the research team considered the trials to be free from the risk of bias posed by a financial conflict of interest ALTERNATIVE THERAPIES. EULAR. the authors reported that none of the included trials employed patient-blinding methods. Two RCTs had a high risk of bias in allocation concealment.43.High risk of bias Xu—TG for Treating LORA 25% Risk of Bias The Cochrane risk of bias is presented in Figure 2 and Figure 3.com Table 1. Abbreviations: ACR. CRP 1/wk—plus NSAIDs. CRP 1/wk—plus NSAIDs. Figure 2. (B) DMARDs—LEF. 20 mg.This article is protected by copyright. ESR. TJC. Key data regarding the 4 included RCTs are summarized in Table 1. American College of Rheumatology. CRP Note: The intervention group in each study used (A) a Tripterygium glycosides tablet and (B) the same DMARD therapy as the control group in that study. methotrexate.44 In addition. 3 ×/d—plus (B) Main Outcomes SJC. erythrocyte sedimentation rate. ESR. Use ISSN#1078-6791. CRP 1/d—plus NSAIDs. all trials had adequately matched participants in the 2 intervention groups and were free from bias due to baseline imbalance.
50 (-22.41 to -0.90 (-14.99 to -0. To subscribe.58 (-1.2 7.51 4. and Xu—TG for Treating LORA .0% -1.35 2.58 5.2 23. B.66) -1.62 to -1.27 22.18 12.13 22.56 3.3% 0.73 (-2. χ2 =5.1% Mean Difference IV. confidence interval.30 (-67.24 (-3. Use ISSN#1078-6791.1% 0. 22 NO.This article is protected by copyright.6% Mean Difference IV.77 2.05 4.30 (-10.90) 124 100. 95% CI -200 -100 Favors Experimental 0 Abbreviations: DMARD.71 23.07 (P < . I2 = 15%.54 24. Random. TJC Study or Subgroup Long41 (2014) Sheng42 (2002) Yang43 (2013) Zhang44 (2011) Study or Subgroup Long41 (2014) Sheng42 (2002) Yang43 (2013) Zhang44 (2011) Study or Subgroup Long41 (2014) Sheng42 (2002) Yang43 (2013) Zhang44 (2011) -1.75 7. I2 = 42%. ESR A.38) -11.27 (P < . CRP.0% -10. Test for overall effect: z = 12. 36 ALTERNATIVE THERAPIES.32).11 0.13 4.70) -11.00001).23 (-11.46 2.8 34. CI.64 to -1.24) -2.0% -10.44 33.83 2.27 33. C. Test for overall effect: z = 20. TJC. 95% CI -50 -25 Favors Experimental Experimental Control Mean SD Total Mean SD Total Weight 0 Mean Difference IV.83 4.00001).01.66 0.13 19. df = 3 (P = .31 2.2% Mean Difference IV.54 1.55 Total (95% CI) 124 Heterogeneity: χ2 =4.41 to -0.41 30.50 (-22.4% 90.65 5.25.26 1. Random. SJC.94 (-10. erythrocyte sedimentation rate.44 (P < . standard deviation. I2 = 27%.3% 2.13 3.7% 51. Random.78 to -9.16).15 24 30 40 30 4.00 (-12. 95% CI -10 -5 Favors Experimental Total (95% CI) 124 Heterogeneity: τ2 =0.68 to -0. Meta-analysis Outcomes All included studies.3% 0.23) 24 30 40 30 23. visit alternative-therapies. 95% CI = -1.26 162 24 30 40 30 22. Test for overall effect: z = 44. The meta-analysis showed superior effects on SJC for Tripterygium glycosides plus the DMARD therapy when compared with the DMARD therapy alone. CRP. 95% CI -1.68 19.com.22) -9.49 19.81 (-2. Effects of Tripterygium Glycosides Plus DMARD Therapy Versus DMARD Therapy on SJC.42 4.59) -0.23 to -9.50 to 12.83 0.77 to -7.51) Experimental Control Mean SD Total Mean SD Total Weight 4.03) -9.28 to 48.1$ 0.11 (P < . and P < .84 24.74 (-2.97) 24 30 40 30 23. NOV/DEC 2016 VOL. Random. 95% CI -11.58.74 (-2. To share or copy this article.1 3.58) -1.82 to -0. compared the effects of Tripterygium glycosides combined with the DMARD therapy to the DMARD therapy alone on the SJC.11.68) 124 100.98 3.56 3. df = 3 (P = . 95% CI -0.02 3.80 to -9. 95% CI -10 -5 Favors Experimental Experimental Control Mean SD Total Mean SD Total Weight Total (95% CI) 124 Heterogeneity: χ2 =3. D.49) -1. swollen joint count.51. df = 3 (P = .52 33. CRP 9.84 4. SD. df = 4.64 to -1. and ESR of patients with LORA. C-reactive protein.00) 24 30 40 30 5 10 Favors Control 5 10 Favors Control 25 50 Favors Control 100 200 Favors Control 0 Mean Difference IV.84 4.24 to -1.41 2. I2 = 34%.55 (-1. Test for overall effect: z = 4. Four RCTs41-44 provided outcome measurements of the SJC.70 to -7.57.52 1. CRP. disease-modifying antirheumatic drug.89 (-5. Random.com Figure 4. Random.0% 24 30 40 30 Mean Difference IV. 2.59) -11.04 0.47 to -9.86) 124 100.52.04 to -1. Random.30) -1.74 (-12.00001).0% 9. with the MD = -1.59) -10.07 21.82 4 1. Random.04 2.1 3. TJC.19 to-0.55 41.21). involving 248 participants. ESR 124 100. 6 Swollen Joint Count.00001).0% 32.25).62 24 30 40 30 34.13 24 30 40 30 6.4% 28. ESR.18 23. SJC Study or Subgroup Long41 (2014) Sheng42 (2002) Yang43 (2013) Zhang44 (2011) Experimental Control Mean SD Total Mean SD Total Weight 3.57 (P = . please visit copyright.14 Total (95% CI) 124 Heterogeneity: χ2 =4.25 (-12.28 33.68 23.8 9.8% 6.76 (-1.50 to -0.5% 95. TJC.18.48) 0 Mean Difference IV.66 2. 95% CI -2.77 (-2.82 to 0. tender joint count.2% Mean Difference IV.76 4.
Tender Joint Count. at I² = 42%. with MD = -10. with MD = -10.51) 8/124 6/124 4 0. considering the fact that the risk of bias still existed in the current study. and P < . with low heterogeneity with χ2 = 4. (3) leucopenia— 4 trials. 6 37 .51. and only 2 RCTs reported the blinding method used by the assessors.23.66) 5/124 6/124 2 2. please visit copyright. 95% CI = -2.01. P = .84 to 3. Erythrocyte Sedimentation Rate.com.01. P = . several common adverse outcomes were reported (Table 2). The pooled results displayed favorable significant effects on CRP for Tripterygium glycosides plus the DMARD therapy when compared with the DMARD therapy alone.57. However. In the review conducted in 2013. when omitting the heterogeneity contributed by the review from Yang et al.98) 8/70 2/70 Abbreviations: RR.23 to -9. as specified in the selection criteria. RR = 1. The study found superior but limited evidence of the effectiveness and safety of Tripterygium glycosides for the treatment of YORA. The current research team explored the discrepancy by including in its meta-analysis all trials comparing Tripterygium glycosides plus DMARD therapy with DMARD therapy alone. Nevertheless. of Adverse Events Adverse Events Nausea and vomiting Liver injury Leukopenia Rash DISCUSSION In the current meta-analysis. and P < .83. Use ISSN#1078-6791. with MD = -1.36 the researchers divided the data into 3 subgroups to minimize the heterogeneity. 22 NO. 95% CI = -2. no significant differences were observed in the risks of (1) nausea and vomiting—4 trials. considering the differences in clinical heterogeneity and varying levels of statistical heterogeneity. and I² = 27% (Figure 4). For selectivereporting bias and other biases. a low heterogeneity. relative risk. P = .66.31.44 the pooled results. The current research team assessed the methodological quality of primary studies using the assessment tool for risk of bias from the Cochrane Handbook.97.67.14. 95% CI = -12. and I2 = 34% (Figure 4).49 to 3. including for the SJC and TJC and the levels of ESR and CRP.11. one trial from Yang et al44 was the obvious outlier in the current meta-analysis. the research team identified 4 RCTs covering 248 participants P Value that involved a comparison of Tripterygium .26 to 2. NOV/DEC 2016 VOL.31 (0.71. 95% CI = -2. with χ2 = 4.This article is protected by copyright. The meta-analysis showed favorable effects on TJC for Tripterygium glycosides plus the DMARD therapy when compared with the DMARD therapy alone. the statistical heterogeneity of analysis for the effect size of the TJC.23.63. No. C-reactive Protein. allocation concealment was conducted in 2 trials. To share or copy this article.15 glycosides and DMARD therapy was found to be superior to DMARD therapy alone in terms of treatment efficacy. 95% CI = 0. the number of trials included in each subgroup was rather small. Furthermore. Sensitivity Analysis Based on the forest plot for the TJC index (Figure 4). the intervention groups using Tripterygium glycosides were not superior to the intervention groups that used DMARD therapy alone in terms of decreasing adverse events. Four RCTs41-44 measured ESR as the outcome.52.25. However. 95% CI = 0.67 (0. Adverse Events. P = .18.06. was substantially decreased.26 to 2. CI.00. and I² = 42% (Figure 4).74. P = . Three RCTs in the current study reported drop-outs and withdrawals.68 to 12. and P < . Four RCTs41-44 provided outcome measurements for the level of CRPs. the result from Yang et al44 was markedly different when compared with the other included studies. RR = 0.15. P = . By eliminating the study of Yang et al44 in the analysis.68 to 12.01. 95% CI = 0. and P < . Nevertheless. (2) liver injury—4 trials. with χ2 = 5. Xu—TG for Treating LORA ALTERNATIVE THERAPIES. RR = 1. P = .97. RR = 2. . Three included trials reported the appropriate methods for randomization. of Intervention Control Studies RR (95% CI) Group Group 4 1. with I² = 0%. and P < .26 to -1.01.47 to -9. visit alternative-therapies.76 Overall.97 (0. the bias of the included RCTs made the team’s conclusions more conservative. None of the studies included in the current study mentioned participant blinding. The results of the subgroup analysis were inconsistent with the current systematic review. Overall. the current research team Events No.21. a 95% CI = -11.76.84 to 3.32.01 were consistent with those in the previous analysis. the results of the meta-analysis may be somewhat optimistic.49 to 3. confidence interval.29. 95% CI = 0. with MD = -2. Moreover.98. In addition.59 therapy alone for the treatment of LORA. Overall. a subgroup analysis that included only 2 RCTs showed no statistically significant differences in the laboratory parameters of Tripterygium glycosides plus DMARD therapy vs DMARD therapy alone. with low heterogeneity with χ2 = 3.16.29) 20/124 12/124 4 1. On inspection of the funnel plot for the TJC index. suggesting the stability of results for the current meta-analysis. To subscribe. Previously.com Table 2.14 glycosides plus DMARD therapy with DMARD . an updated meta-analyses36 published in 2013 had been carried out to examine the effectiveness and safety of Tripterygium glycosides. those results should be interpreted with caution.15. and (4) rashes—2 trials. P = . To explore that issue. For the comparisons of Tripterygium glycosides plus the DMARD therapy with DMARD therapy alone.50 to -0.83 (0. and a high heterogeneity. the current research team made a judgment that all included RCTs were of low risk.70 to -1. the current systematic review specifically focused on populations of older adults rather than young-onset clients. with MD = -1. Four RCTs41-44 used the TJC as an outcome for improvement of LORA after treatment. Therefore. I² = 15% (Figure 4).41.73. The meta-analysis showed superior effects on ESR for Tripterygium glycosides plus the DMARD therapy when compared with the DMARD therapy alone. the combined use of Tripterygium .
results of patients’ assessments of global pain. and cartilage-protective mechanisms. Fourth. Furthermore. the most common adverse effects of Tripterygium glycosides were gastrointestinal discomfort. has been well documented. clinical trials concerning the Tripterygium glycosides should be reported following the CONSORT statements. Third.45 Moreover. Numerous published studies describe the potential molecular mechanism for the action of Tripterygium glycosides. large-scale. the current research team did not conduct an analysis of the publication bias due to the small number of included trials. However. visit alternative-therapies. in addition to the current objective measurements. Tutuncu et al22 conducted an investigation and concluded that LORA patients may receive a lower dosage of methotrexate when compared with YORA patients. 6 the pathogenesis and progression of RA. and rashes.com. identification of the optimal DMARDs could be an important issue for LORA patients. the other studies used the ACR 1987 criteria. To share or copy this article. the results from the TJC did not produce material differences after eliminating the study by Yang et al from the analysis. the follow-up period for all included trials was 6 months. Previous studies have suggested that Tripterygium glycosides can inhibit the release of inflammatory cytokines both in T lymphocytes and macrophages47. the details concerning reproductive toxicity could not be evaluated further due to lack of information. Therefore.48 and can induce the production of nitric oxide49 and prostaglandin E250 during 38 ALTERNATIVE THERAPIES. and improve physical function in LORA patients. liver injury. please visit copyright. Therefore. Serious adverse events associated with the use of Tripterygium glycosides have been well documented. rigorous RCTs will be necessary to confirm the efficacy and safety profile of Tripterygium glycosides for treating LORA. limiting the results specifically to that subset of Asian populations.This article is protected by copyright. the pharmacological action of Tripterygium glycosides includes anti-inflammatory.34 In addition. To subscribe. However.53 In the future. By eliminating the study by Yang et al from the statistical analysis. randomized. which shed a light on the possible molecular mechanisms involved. In the future. Use ISSN#1078-6791. Sylvester et al52 have reported that the protective effects on cartilage of Tripterygium glycosides can mostly be attributed to the inhibition of cytokine-stimulated MMP-3 by impairing activating protein-1 and NF-kB binding activity. as a major side effect. Furthermore. In the current study. and a health-assessment questionnaire should be analyzed in future research. In summary. causing a major side effect that can significantly decrease the quality of life46 of male patients. the treatment effects may have been overestimated. when compared with YORA patients. Tripterygium glycosides are attractive for the older adult as a novel botanical drug for the treatment of rheumatoid arthritis. LORA patients showed lower fertility requirements. and most of those side effects were either resolved spontaneously or after administering an adjusted dose for the treatment. only a few published trials have reported on the safety and efficacy of Tripterygium glycosides for treating LORA. double-blind trials are warranted in Western countries. As more RCTs become available in the literature. the number of studies included in the current systematic review and meta-analysis was small. Due to the lack of specific placebo effects. In all included RCTs in the current study. all included RCTs were carried out on Chinese populations. no statistically significant differences occurred between the 2 groups. To draw firm conclusions on their effectiveness as an intervention for treating RA is difficult due to the small sample sizes of the eligible RCTs and the high risk of bias among the available RCTs. 22 NO. NOV/DEC 2016 VOL. CONCLUSIONS Currently. which is funded by the UK National Institute for Health Research. in the future. Xu—TG for Treating LORA .55 Second. those changes may also contribute to an increased severity of adverse drug events in older patients when compared with the younger populations.com noted that the study by Yang et al followed the RA diagnostic criteria according to ACR/EULAR 2009. In the current systematic review. LORA is possibly a more heterogeneous disease than YORA. an improvement in the heterogeneity index was observed. and changes in the immune and endocrine systems with aging may explain the differences in characteristics between LORA and YORA. the current research team will update its systematic review in the future. immunosuppressive. Similar results have been reported by Lv et al33 and Tao et al. Limitations A number of important gaps exist in the current metaanalysis that should be addressed in future research.56 which might contribute to a bias. Tripterygium glycosides are considered to behave like herbal DMARDs and may contribute to the reduction of inflammation. and it is noteworthy that a malfunction of the reproductive system can occur. Unfortunately. leukopenia. However. placebo-controlled. multicenter. rigorously designed. a possibility exists that negative results were less likely to be published. In 2006. no placebo-controlled trials were included in the trials discussed in the current meta-analysis. the use of different diagnostic criteria might have contributed to the different results on the TJC index. having a placebo comparable to the specific effects of Tripterygium glycosides may be essential and critical in an RCT. Last. The current research team had registered the meta-analysis in PROSPERO. investigators should be encouraged to provide more details about the adverse events from Tripterygium glycosides for an adequate assessment of safety. Therefore. Another study51 has demonstrated that Tripterygium glycosides may be potent inhibitors of type 2 collagen-induced arthritis in rats. Considering that all included trials were performed in China. it is noteworthy that the malfunction of the reproductive system.54. despite similar levels of disease progression. in terms of the patients’ safety. In addition. physicians’ assessments of disease activity. First. Fifth. Hence. prevent or limit joint damage. warranting the analyses of long-term data on trial outcomes in the future.
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