Humans ; Spondylarthritis/drug therapy* ; Spondylitis, Ankylosing/drug therapy* ; China

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.
Capsules ; China ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Network Meta-Analysis ; Nonprescription Drugs/therapeutic use* ; Spondylitis, Ankylosing/drug therapy*

To investigate the efficacy of Huangqin Qingre Chubi Capsules(HQC) in patients with ankylosing spondylitis(AS) and its effect on oxidative stress, and to explore its possible mechanism. Fifty-eight cases of AS patients were randomly divided into HQC group and salazosulfapyridine(SASP) group. Another 30 healthy people were employed as a control group. Superoxide dismutase(SOD), total antioxidant capacity(TAOC), malondialdehyde(MDA), lipid peroxidatio(LPO), interleukin-1β(IL-1β), IL-10, IL-4, and tumor necrosis factor-α(TNF-α) were detected by ELISA. The mRNA expression levels of AMP-activated protein kinase(AMPK-α), forkhead box O3a(FOXO3a), manganese superoxide dismutase(MnSOD), and peroxisome proliferator-activated receptor gamma(PPARγ) were detected by Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expression levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, and PPARγ were detected by Western blot. A questionnaire was used to evaluate the disease activity score and observe the clinical efficacy of HQC in AS patients. The levels of MDA, LPO, TNF-α, and IL-1β were significantly increased in the peripheral blood of AS patients, and SOD, TAOC, IL-4, IL-10 levels were significantly decreased. After HQC treatment, scores of disease active indexes were all decreased, and its clinical efficacy was significantly higher than that in SASP group. After HQC treatment, TAOC, SOD, IL-4, IL-10 were increased and MDA, LPO, TNF-α, IL-1β were decreased; mRNA levels of AMPK-α, FOXO3a, MnSOD, PPARγ and protein levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, PPARγ were increased(P<0.01 or P<0.05). HQC can effectively improve the clinical symptoms and oxidative stress of AS patients, and its mechanism may be related to activating PPARγ and up-regulating AMPK/FOXO3a signal pathway.
AMP-Activated Protein Kinases/metabolism* ; Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Forkhead Box Protein O3/metabolism* ; Humans ; Oxidative Stress ; PPAR gamma/metabolism* ; Scutellaria baicalensis/chemistry* ; Signal Transduction ; Spondylitis, Ankylosing/drug therapy* ; Sulfasalazine/therapeutic use*

BACKGROUND: Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study. METHODS: MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China). RESULTS: Of 458 patients (secukinumab 150 mg, N = 305; placebo, N = 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52. CONCLUSIONS: Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations. TRIAL REGISTRATION ClinicalTrials.gov, NCT02896127; https://clinicaltrials.gov/ct2/show/NCT02896127?term=NCT02896127&draw=2&rank=1.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Spondylitis, Ankylosing/drug therapy* ; Treatment Outcome

OBJECTIVETo observe the clinical effect of Chinese medical (CM) syndrome differentiation based Chinese herbs and recombinant human tumor necrosis factor receptor II-antibody fusion protein (etanercept) for treating ankylosing spondylitis (AS) patients.

METHODSTotally 35 AS patients were treated with syndrome differentiation based Chinese herbs and etanercept. Reinforcing Shen and strengthening Du channel, activating meridians to stop pain was principle used in syndrome differentiation based treatment. Etanercept was subcutaneously injected, 25 mg each time; twice per week for the first three months and once a week for the latter three months. The clinical efficacy was evaluated after 3 and 6 months of treatment. Meanwhile, ASAS20 and ASAS50 standards arriving rates were also observed. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), visual analog score (VAS) for spine pain, VAS for night pain, patient global assessment (PGA), VAS for physician global assessment, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, cervical rotation, Schober improved test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were observed before treatment, 3 and 6 months after treatment.

RESULTSCompared with before treatment, BASDAI, BASFI, VAS for spine pain, night pain, physician global assessment, PGA, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, Schober improved test, ESR, and CRP all decreased after 3 and 6 months of treatment, with statistical difference (P < 0.05). Cervical rotation also decreased after 6 months of treatment, with statistical difference (P < 0.05). Compared with 3 months of treatment, total effective rate of CM syndrome, ASAS20 and ASAS50 standards arriving rates increased after 6 months of treatment, with statistical difference (P < 0.05). There were statistical differences in all indices mentioned above between after 3 months of treatment and after 6 months of treatment (P < 0.05).

CONCLUSIONSyndrome differentiation based Chinese herbs combined etanercept could alleviate inflammatory reaction favorably, control the progression of active AS, and improve joint functions.

Disease Progression ; Drugs, Chinese Herbal ; therapeutic use ; Etanercept ; therapeutic use ; Humans ; Pain ; prevention & control ; Pain Management ; Spondylitis, Ankylosing ; drug therapy ; Treatment Outcome

OBJECTIVETo observe the effect of Xinfeng Capsule (XFC) on ankylosing spondylitis (AS) patients' symptoms and signs, serum immunoglobulin levels, peripheral blood lymphocyte autophagy protein, autophagy gene, and to explore its mechanism.

METHODSTotally 59 AS patients were assigned to the treatment group (39 cases) and the control group (20 cases) according to random digit table. Patients in the treatment group received XFC, 0.5 g each pill, three pills each time, 3 times per day, while those in the control group received sulfasalazine (SASP), 0.25 g per tablet, 4 tablets each time, twice per day. Three months consisted of one therapeutic course. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were statistically calculated. Serum immunoglobulins (IgG1, IgG2, IgG3, IgG4, IgA , SIgA, and IgM) were detected using ELISA. Changes of Beclin1, LC3-II, phosphatidylinositol 3-kinase (PI3K), Akt, the mammalian target of rapamycin (mTOR) were detected using Western blot. Serum autophagy related genes such as Atg1, Atg5, Atg12, Atg13, and Atg17 were detected using the polymerase chain reaction (PCR). The correlation between immunoglobulin subtypes and autophagy gene in AS patients using Spearman correlation.

RESULTSCompared with before treatment, BASDAI, IgG1, lgG3, and IgA decreased (P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.01); ATG1, ATG12, ATG13, and ATG17 mRNA expressions decreased, ATG5 mRNA expression increased (P < 0.01) in the treatment group. But BASDAI, IgG1, and IgA levels decreased (P < 0.05, P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.05); ATG1 and ATG13 mRNA expressions decreased (P < 0.05, P < 0.01) in the control group. Compared with the control group, BASDAI, IgG1, and IgA levels decreased (P < 0.05); PI3K, Akt, mTOR protein expressions decreased (P < 0.01); ATG12 and ATG17 mRNA expression decreased, ATG5 mRNA expression increased (P < 0.01) in the XFC group. Correlation analysis showed AS patients' IgG1, IgG2, IgG3, IgA, SIgA, IgM had negative correlation with ATG17; IgG4 and ATG17 were positively correlated (P < 0.05, P < 0.01).

CONCLUSIONXFC could elevate clinical efficacy of AS patients and enhance their autophagy, which might be achieved by acting on PI3K/Akt/mTOR signal, affecting autophagy gene and autophagy protein expression, taking part in the regulation of proliferation and differentiation of lymphocyte B, and strengthen humoral immunity.

Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; Beclin-1 ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Lymphocytes ; drug effects ; Membrane Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Spondylitis, Ankylosing ; drug therapy ; Sulfasalazine ; therapeutic use ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVETo evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients.

METHODSA prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment.

RESULTSAfter three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group.

CONCLUSIONBSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

Asian Continental Ancestry Group ; Biomedical Research ; Blood Sedimentation ; C-Reactive Protein ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; Prospective Studies ; Safety ; Spondylitis, Ankylosing ; drug therapy

Adult ; Humans ; Methylprednisolone ; therapeutic use ; Optic Neuritis ; diagnosis ; drug therapy ; etiology ; Spondylitis, Ankylosing ; complications

OBJECTIVETo evaluate the clinical efficacy and safety of Qiangji Recipe (QR) in ad- junctive treatment of axial undifferentiated spondyloarthritis (axuSpA) through a four-week open study.

METHODSFifty-four axuSpA patients of Shen-deficiency Du-channel cold syndrome (SDDCS) in line with inclusive criteria were recruited and assigned to the treatment group and the control group according to random digit table, 27 in each group. Patients in the control group took Celecoxib Capsule (0.2 g each time, twice per day). Patients in the treatment group additionally took QR (consisting of Herba Epimedii 15 g, antler glue 15 g, Cibotium Barometz 15 g, eucommia bark 20 g, dipsacus asper 10 g, two toothed achyranthes root 15 g, drynaria 15 g, Taxillus Chinensis 20 g, ground beetle 10 g, scorpion 5 g, wild celery 10 g, notopterygium incisium 10 g, cow-fat seed 10 g, white mustard seed 6 g, and licorice root 6 g, one dose per day, twice daily). The therapeutic course for all was 4 weeks. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), total body pain and spinal pain, patient and physician global assessment on a four-point scale, the Ankylosing Spondylitis Quality of Life (ASQoL), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after 4 weeks of treatment. The primary end point in this study was the proportion of patients with a 20%improvement response accord- ing to the ASAS International Working Group Criteria (ASAS 20 responders) at week 4.

RESULTSTotally 50 patients completed this trial, 26 in the treatment group and 24 in the control group. Improvement of BASDAI, BASFI, BASMI, ASQoL, ESR, and CRP was shown in both groups after treatment. Better effect was shown in the treatment group in all indices except ESR and BASMI after treatment (P < 0.05, P < 0.01). Twenty cases (accounting for 76.92%) in the treatment group achieved ASAS 20 response at week 4, while 12 cases (accounting for 50.00%) in the control group achieved ASAS 20 response at week 4 (P < 0.05). No obvious adverse reaction occurred in the two groups.

CONCLUSIONQR combined Celecoxib Capsule showed better effect in treating axuSpA patients than using Celecoxib Capsule alone.

Blood Sedimentation ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; Quality of Life ; Spondylitis, Ankylosing ; drug therapy

OBJECTIVETo explore changes of B and T lymphocyte attenuator (BTLA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAOC), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA) in ankylosing spondylitis (AS) patients, and the effect of Xinfeng Capsule (XFC) on them.

METHODSTotally 120 AS patients were assigned to two groups according to random digit table method, the XFC group (3 XFC pills each time, 3 times a day) and the SASP group (4 SASP tablets each time, twice a day), 60 in each group. All patients were treated for 3 months. Another 60 healthy subjects were recruited as a healthy control group. The expression frequency and activation levels of BTLA were detected using flow cytometry. Serum oxidative stress indices (such as SOD and CAT, TAOC, ROS, RNS, MDA) and contents of cytokines [tumor necrosis factor α (TNF-α), IL-1β, IL-4, and IL-10] were detected using enzyme-linked immunoassay (ELISA). Erythrocyte sedimentation rate (ESR) was detected using Westergren method. High-sensitivity C-reactive protein (Hs-CRP) was detected using HITACHI 7060 type automatic biochemical analyzer. Clinical efficacies of ASAS 20 and BASDAI50 were assessed using VAS. Correlation analysis between scoring for quality of life and BTLA expression frequency was performed.

RESULTS(1) Clinical efficacies of ASAS 20 and BASDAI50 were significantly better in the XFC group than in the SASP group (P < 0.01). (2) Compared with the healthy control group, BTLA expressions in the peripheral blood of AS patients decreased significantly (P <0. 05); SOD, CAT, and TAOC values significantly decreased (P < 0.01, P < 0.05); ROS, RNS, and MDA values significantly increased (P < 0.01, P < 0.05); TNF-α, IL-1β, ESR, and Hs-CRP values significantly increased (P < 0.01); IL-4 and IL-10 values decreased significantly (P < 0.01, P < 0.05). (3) Compared with pre-treatment in the same group, BTLA/CD19 + B, BTLA/CD24 + B, SOD, TAOC, IL-4, SF-36 [physical functioning (PF), social functioning (SF), role limitation due to physical problems (RP), role limitation due to emotional problems (RE), body pain (BP), mental health (MH), vitality (VT), general health (GH)] were significantly elevated; ROS, MDA, TNF-α, ESR, Hs- CRP, VAS, BASDAI and BASFI, BAS-G were significantly lower in the peripheral blood of the two groups after treatment (P < 0.01, P < 0.05). Better effect was shown in the XFC group in elevating BTLA/CD19+ B, BTLA/CD24 + B, SOD, TAOC, IL-10, BP, MH, VT, and SF; and lowering ROS, IL-1β, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI, and BAS-G (P < 0.01, P < 0.05). (4) Pearson correlation analysis showed, BTLA/CD19 + B expression of the peripheral blood was positively correlated with SOD, CAT, TAOC, IL-4, IL-10, GH, RP, BP, and SF (r = 0.431, 0.325, 0.318, 0.316, 0.348, 0.314, 0.358, 0.318, 0.326, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, MDA, TNF-α, IL-1β, ESR, VAS, and BASDAI (r = -0.342, -0.368, -0.334, -0.354, -0.324, -0.372, -0.342, respectively, P < 0.05, P < 0.01). BTLA/CD24 B expression of the peripheral blood was positively correlated with SOD, TAOC, IL-4, IL-10, GH, RP, BP, SF, RE, MH, VT (r = 0.358, 0.352, 0.372, 0.436, 0.435, 0.326, 0.352, 0.345, 0.326, 0.343, 0.332, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, RNS, MDA, ESR, Hs-CRP, VAS, BASDAI, and BASFI (r = -0.447, -0.336, -0.405, -0. 395, -0. 358, -0.436, -0.338, -0.425, respectively, P < 0.05, P < 0.01).

CONCLUSIONXFC could improve BTLA expression in the peripheral blood of AS patients, negatively regulate activation and proliferation of B cells, and reduce abnormal immune responses and oxidative stress injury, thereby effectively alleviating joint stiffness and pain.

B-Lymphocytes ; physiology ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Capsules ; Catalase ; metabolism ; Cytokines ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Flow Cytometry ; Humans ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-4 ; metabolism ; Malondialdehyde ; metabolism ; Oxidative Stress ; Quality of Life ; Reactive Oxygen Species ; Spondylitis, Ankylosing ; drug therapy ; Superoxide Dismutase ; metabolism ; T-Lymphocytes ; physiology ; Tumor Necrosis Factor-alpha ; metabolism