ObjectiveTo investigate the efficacy and safety of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR:Fc) for treatment of active rheumatoid arthritis (RA). MethodsThis study included 86 patients with active rheumatoid arthritis treated between September 2011 and January 2013. They were divided into two groups randomly. Forty-three patients in the treatment group received rhTNFR:Fc (25 mg, twice a week) by subcutaneous injection and methotrexate (MTX) (10 mg, orally once a week), and the other 43 patients in the contrast group received MTX (10 mg, orally once a week), hydroxychloroquine (100 mg, orally twice daily), and leflunomide (10 mg, orally once daily). The clinical efficacy of the treatments 12 weeks later were compared between the two groups. American College of Rheumatology (ACR) 20, 50, and 70 evaluation criteria were used for efficacy evaluation. ResultsThe ACR 20, 50 and 70 effective rates in 4, 8 and 12 weeks after the treatment in the treatment group were significantly higher than those in the control group (P<0.05). The seven indicators including the duration of morning stiffness, joint tenderness index, joint swelling index, erythrocyte sedimentation rate, C-reactive protein, platelets and rheumatoid factors within 12 weeks after treatment were significantly improved in both the two groups, and the improvements in the treatment group were more significant (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). ConclusionRhTNFR:Fc is effecive and safe in treating active RA.
Objectives To systematically review the efficacy and safety of certolizumab pegol (CZP) plus methotrexate (MTX) for active rheumatoid arthritis. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) on CZP plus MTX vs. MTX plus placebo for active rheumatoid arthritis from inception to May, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, data were analyzed by using Stata 11.0 software. Results Seven RCTs were included. The results of meta-analysis showed the CZP plus MTX group was superior to MTX plus placebo group in ACR20 (CZP400 mg: RR=2.86, 95%CI 1.70 to 4.79, P<0.001; CZP200 mg: RR=3.76, 95%CI 2.59, 5.46, P<0.001), ACR50 (CZP400 mg: RR=3.91, 95%CI 2.10 to 7.27, P<0.001; CZP200 mg: RR=4.86, 95%CI 3.20 to 7.39, P<0.001), and ACR70 (CZP400 mg: RR=5.65, 95%CI 1.99 to 16.06, P=0.001; CZP200 mg: RR=10.08, 95%CI 5.11 to 19.89, P<0.001). The CZP plus MTX group was also superior to MTX plus placebo group in swollen joint counts (SMD=–12.72, 95%CI –15.39 to –10.06,P<0.001), tender joint counts (SMD=–11.54, 95%CI –13.97 to –9.11,P<0.001), doctor's global assessment of disease activity (SMD=–11.78, 95%CI –13.81 to –9.75,P<0.001), patient's global assessment of disease activity (SMD=–9.62, 95%CI –11.09 to –8.15,P<0.001), and patient's assessment of pain (SMD=–9.10, 95%CI –10.91 to –7.30,P<0.001) and HAQ (SMD=–7.74, 95%CI –8.99, –6.49,P<0.001), respectively. However, the incidence of adverse events in CZP plus MTX group was higher than that in MTX plus placebo group. Conclusions CZP plus MTX is superior to MTX plus placebo for treatment of active rheumatoid arthritis but with higher adverse events. Due to limited quantity and quality of the included studies, the above conclusions are still needed to be verified by more high-quality studies.
Circular RNAs (circRNAs) are a novel class of non-coding RNAs, which are more stable than linear RNAs for their closed circular structure by covalent bond. CircRNAs exist in a large variety of cells and regulate the expressions of target genes. Moreover, circRNAs are closely related to various diseases and have a potential value as biomarkers and prognostic markers clinically. In this article, the classification and biological functions of circRNA molecules (including being as microRNA sponges, regulating gene transcription, regulating RNA binding protein and the potential translation function) are summarized, and the latest research progress of circRNAs in rheumatoid arthritis is reviewed.
【Abstract】 Objective To explore the effectiveness of multiple joint arthroplasty in treating lower limb joint disease. Methods Between January 2000 and December 2007, 5 patients with lower limb joint disease (three or more joints were involved) were treated with total hip and knee arthroplasty. There were 3 males and 2 females, aged from 27 to 59 years (mean, 41.8 years). Two patients had ankylosing spondylitis and 3 had rheumatoid arthritis, whose hip and knee joints were involved. Four patients lost the ability of walking preoperatively, 1 patient could only walk with crutch. The Harris score was 24 ± 24 and the Hospital for Special Surgery (HSS) score was 28 ± 15. All patients underwent multiple joint arthroplasty simultaneously (2 cases) or multiple-stage (3 cases). Results Wounds healed by first intention in all patients. In 1 patient who had dislocation of the hip after operation, manipulative reduction and immobilization with skin traction were given for 3 weeks, and no dislocation occurred; in 2 patients who had early sign of anemia, blood transfusion was given. All patients were followed up 46-140 months with an average of 75 months. The patients could walk normally, and had no difficulty in upstairs and downstairs. The stability of the hip and knee was good, and no joint infection or loosening occurred. The Harris score was 88 ± 6 at last follow-up, showing significant difference when compared with the preoperative score (t=8.16, P=0.00); the HSS score was 86 ± 6, showing significant difference when compared with the preoperative score (t=13.96, P=0.00). Conclusion Multiple joint arthroplasty is an effective treatment method in patients with lower limb joint disease, which can significantly improve life quality of patients.
ObjectiveTo compare the cost-effectiveness of etanercept combined with methotrexate to methotrexate plus placebo in the treatment of rheumatoid arthritis and to provide references for clinical practice.MethodsDecision tree model was developed to estimate the cost-effectiveness from the perspective of the health care system by TreeAge Pro 2016 software. The cost-effectiveness of the two treatments were compared by incremental analysis, and the robustness of the results were analyzed by sensitivity analysis.ResultsThe cost of etanercept combined methotrexate group in one year duration was ¥212 692, the effective rate (ACR50) was 66.4%; the cost of methotrexate combined with placebo group in one year duration was ¥572, the effective rate (ACR50) was 40.6%. The incremental cost-effectiveness ratio of two groups was ¥818 000/person, and the sensitivity analysis showed that the results were robust.ConclusionEtanercept combined methotrexate is significant more effective than methotrexat. But the cost of etanercept combined methotrexate is too high to afford and is not economical compared to methotrexate.
Therapeutic drug monitoring (TDM) has been more widely used in small molecule agents, such as immuno-suppressants, antiepileptic drugs and antibiotics, with less attention in the field of therapeutic biological agents. Monoclonal drugs represented by tumor necrosis factor alpha (TNF-α) inhibitors have shown a good relationship between exposure and efficacy in clinical studies. There are corresponding guidelines and consensus for the recommendations of TDM based on current research evidence. Therefore, this paper introduced the current evidence, strategies and considerations for TDM in the optimal treatment of adalimumab from the perspective of adalimumab TDM to provide references for the clinical practice of adalimumab TDM.
ObjectiveTo investigate the potential causal relationship between four types of reproductive behaviors and rheumatoid arthritis (RA), with the goal of establishing a theoretical foundation for clinical prevention and treatment strategies. MethodsPooled gene-wide association study (GWAS) data were obtained from large publicly searchable databases. Four characteristics like menarche, menopause, the age of first pregnancy and the age of last pregnancy, which related to reproductive behavior were selected as the exposure factors and RA as the outcome factors. Single nucleotide polymorphisms (SNPs), which were strongly correlated with the phenotype of the exposure factors, were screened as the instrumental variables, and two-sample Mendelian randomization analyses were used to assess the potential causal relationship between the exposure and the disease. Results① The Mendelian randomization analysis utilizing the inverse variance weighted method on two distinct samples revealed a significant negative correlation between the age of first pregnancy and last pregnancy with the risk of RA (OR=0.91, 95%CI 0.85 to 0.98, P=0.011; OR=0.54, 95%CI 0.31 to 0.93, P=0.026). Conversely, no causal relationship was observed between menarche and menopause with RA. Sensitivity analysis confirmed the robustness of the causal relationship, while MR Egger intercept analysis did not identify any potential horizontal pleiotropy (Page of first gestation -RA=0.169, Page of last gestation -RA=0.283). ② Reverse Mendelian randomization analysis revealed a significant positive causal association between RA and the age of first pregnancy, while no causal relationship was observed with the age of last pregnancy (OR=1.07, 95%CI 1.02 to 1.11, P=0.001). ③ Multivariate Mendelian randomization analysis demonstrated that both the age of first pregnancy and last pregnancy in women were inversely associated with the risk of RA (OR=0.88, 95%CI 0.80 to 0.97, P=0.010; OR=0.68, 95%CI 0.48 to 0.97, P=0.033). ④ There existed a negative correlation between the age of pregnancy in women and the risk of developing RA, suggesting a potential protective effect. ConclusionPregnancy age may have a negative causal relationship with the risk of RA, while menarche and menopause have no causal relationship with RA.
Rheumatoid arthritis is a chronic inflammatory disorder. It is characterized by a chronic polyarthritis that primarily affects the peripheral joints and related periarticular tissues. To a patient with rheumatoid arthritis, we searched the evidence and indentified the best available therapy for him: ① Ibuprofen was used to relieve pain. ② Methopterin ivgtt qw and oral methopterin after the discharge for 12 months. ③ Oral omeprazole 20 mg/d to prevent peptic ulcear. ④ Administration with fish oil and physical exercises after discharge were recommended.
Rheumatoid arthritis (RA) is a common systemic autoimmune disease with complicated pathogenesis. Symmetric pain and swelling in multiple joints are the primary clinical symptoms. The early diagnosis and treatment significantly contribute to the better prognosis of RA patients. However, there are still a lot of obstacles in the way of diagnosing and treating RA, and innovative models are urgently needed. As an innovative cross-research model, the applications of the combination of medicine and engineering in the biomedical field present a good prospect, which is expected to improve the demands and defects of traditional RA diagnosis and treatment. Herein, this article reviewed the research progress of the new technologies’ applications in RA diagnosis and treatment in recent years, in order to broaden the new strategies of RA precision diagnosis and treatment.
ObjectivesTo review the pharmacoeconomic evaluation of rheumatoid arthritis patients with an inadequate efficacy or intolerance with conventional synthetic disease modifying antirheumatic drugs (csDMARDs).MethodsCNKI, WanFang Data, VIP, PubMed, EMbase, Web of Science and The Cochrane Library were electronically searched to collect pharmacoeconomic studies about rheumatoid arthritis patients with an inadequate efficacy or intolerance with csDMARDs from inception to February 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of the included studies, then, descriptive analysis was performed.ResultsA total of 16 studies were included, where most compared the economics of different treatment methods from the perspective of the payer by cohort or individual model. The economic costs in the studies were primarily on direct cost. Sensitivity analyses were used to prove the robustness of the main analysis in each study. Biological disease-modifying antirheumatic drugs (bDMARDs) might be more cost-effective than csDMARDs. In addition, compared with the bDMARDs, new-marketed targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) might be more cost-effective.ConclusionsIt could be considered to implement more new marketed tsDMARDs to improve patients’ condition to reduce the economic burden and optimize the allocation of health care resources.