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 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

Antineoplastic Agents ; therapeutic use ; Back Pain ; complications ; drug therapy ; Blood Sedimentation ; Hemoglobins ; metabolism ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Multiple Myeloma ; complications ; drug therapy ; therapy ; Spondylitis, Ankylosing ; complications ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the relationship of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) with the occurrence of ankylosing spondylitis (AS), and the effects of Bushen Tongdu Decoction (BTD) on serum TNF-alpha and TGF-beta1, levels in patients.

METHODSSeventy five AS patients were assigned to two groups, 30 in the group I treated with Azulfidine and35 in the group II treated with BTD. ELISA was adopted to detect the levels of TNF-alpha and TGF-beta1, in patients before and after 24-week treatment. Meantime, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured as well. Besides, the levels of TNF-alpha and TGF-beta1 in 30 healthy persons were also detected for normal control.

RESULTSBefore treatment, as compared with normal control, the TNF-alpha increased and TGF-beta1 decreased (P < 0.01) in the two treatment groups; the serum level of TNF-alpha was positively correlated with ESR and CRP (r = 0.296, r = 0.249; P < 0.05), but the serum level of TGF-beta1 showed no correlation with them (r = -0.222, r = -0.203; P > 0.05). After treatment, TGF-beta1 increased, while TNF-alpha, CRP and ESR decreased in group II (P < 0.01).

CONCLUSIONBTD can regulate TNF-alpha and TGF-beta1 levels to suppress the immune inflammatory reaction so as to treat AS.

Adult ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Spondylitis, Ankylosing ; blood ; drug therapy ; physiopathology ; Transforming Growth Factor beta1 ; blood ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

OBJECTIVETo investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).

METHODSThe serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls.

RESULTSThe serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p<0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p<0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p<0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P<0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001).

CONCLUSIONSerum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.

Adolescent ; Adult ; Aged ; Antirheumatic Agents ; therapeutic use ; Biomarkers ; blood ; Etanercept ; Female ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; blood ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Spondylitis, Ankylosing ; blood ; drug therapy ; Young Adult

OBJECTIVEIn order to investigate the roles of metalloproteinase in inflammatory bone destruction in ankylosing spondylitis (AS), and analyze the mechanism of preventing inflammatory bone destruction of Bushen Qiangdu decoction (BSQDD) in AS cases. Comparisons were made on the expressions of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by peripheral blood mononuclear cells (PBMC) between AS patients and healthy controls. The effect of BSQDD was investigated on the expression and of MMP-9 and TIMP-1 produced by PBMC in AS patients.

METHODSFrom March 2005 to March 2006, 30 active AS cases of Kidney-asthenia, Du-cold and blood-stasis syndrome were selected as patients group in the China-Japan Friendship Hospital. There are 27 male patients and 3 female patients. The age range is from 16 to 45, averaging (30.8 +/- 8.8) years. Disease duration is from 0.5 to 10 years. Cases received three-month BSQDD treatment were considered as the treatment group. Twenty healthy persons were included in the control group. Serum and PBMC were separated. The PBMC were stimulated by PHA and PMA, and the supernatant was collected. The mRNA expression of MMP-9 and TIMP-1 in PBMC was analyzed by RT-PCR. The content of MMP-9 and TIMP-1 in serum and culture supernatant of PBMC were detected by ELISA.

RESULTSCompared with health control group, the serum concentration of MMP-9 and TIMP-1 in patients group before treatment increased (P<0.01, P<0.05), but the level of MMP-9 and TIMP-1 in the serum of patients after treatment decreased compared with pre-treatment cases (P<0.05). Furthermore,compared with health control group, PBMC of patients group before treatment expressed higher levels of MMP-9 and TIMP-1 both on transcript level and at protein level (P<0.01, P<0.05), and the expression levels of MMP-9 and TIMP-1 in PBMC in patients after treatment both on transcript level and at protein level was down-regulated compared with pre-treatment (P<0.01, P<0.05).

CONCLUSIONPBMC of AS patients had a higher potential capacity for MMP-9 and TIMP-1. BSQDD possibly prevented inflammatory bone destruction of AS through inhibiting production of MMP-9 and TIMP-1 produced by PBMC.

Adolescent ; Adult ; Case-Control Studies ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; blood ; genetics ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Retrospective Studies ; Spondylitis, Ankylosing ; blood ; drug therapy ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; blood ; genetics ; Young Adult

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 confirm the efficacy and safety of Jitongning Capsule in the treatment of ankylosing spondylitis (AS).

METHODSA total of 120 AS patients with early-intermediate were randomly and equally assigned to Jitongning Capsule group and sulfasalazine group. Jitongning Capsule was orally taken 4.5 g per day and sulfasalazine was orally taken 2 g daily for 12 months. The primary endpoint was the proportion of patients achieving the Assessment in Ankylosing Spondylitis 20 (ASAS 20), secondary end points included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), patient's global assessment by VAS rating, spinal pain, general pain and night pain, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMC) of AS patients were measured.

RESULTSA total of 111 patients completed the study. There were 58 patients in Jitongning group and 53 patients in sulfasalazine group. Both drugs showed mild and occasional side effects. After treated by Jitongning Capsule and sulfasalazine, the proportion of ASAS20 responders at 12 month was 72.41% (42/58) and 67.92% (36/53) respectively. Both Jitongning Capsule and sulfasalazine treatment induced significant decrease in the proportion of CD4(+)T cell and CD8(+)T cell expressing TNF-α and IFN-γ at 12-month of treatment compared with baseline values (P<0.05).

CONCLUSIONJitongning Capsule are effective in a setting close to real-life medical care with a sustained improvement in signs and symptoms of AS, and reduce cytokine levels in PBMC. It showed comparable effects to sulfasalazine.

Adult ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; CD4-Positive T-Lymphocytes ; drug effects ; secretion ; CD8-Positive T-Lymphocytes ; drug effects ; secretion ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Flow Cytometry ; Humans ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; Male ; Middle Aged ; Spondylitis, Ankylosing ; blood ; drug therapy ; immunology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; secretion ; Young Adult

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFalpha and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFalpha, including type and treatment duration. The median duration of anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/*adverse effects/*therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma/*blood ; Latent Tuberculosis/*blood/*chemically induced/diagnosis ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Spondylitis, Ankylosing/blood/*drug therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

OBJECTIVETo evaluate the efficacy and safety of etanercept, a tumor necrosis factor (TNF)-alpha inhibitor, in the treatment of ankylosing spondylitis (AS), and investigate its effect on serum levels of matrix metalloproteinase-3 (MMP-3).

METHODSForty-eight patients with AS received etanercept 25 mg twice a week for a treatment course of 12 weeks. The patients' symptoms, signs, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and side effects were observed before and after the treatment. The serum levels of MMP-3 was determined using enzyme-linked immunosorbent assay (ELISA).

RESULTSAll the patients completed the treatment. The degree of spinal pain and pain at night, the duration of morning stiffness, the finger-to-floor distance, BASDAI and BASFI were significantly improved after the treatment (P<0.05). Etanercept treatment resulted in a significant reduction in serum MMP-3 level in the AS patients to 31.22-/+10.26 ng/ml as compared with the level before treatment (46.17-/+25.74 ng/ml, P<0.05). The reduction of serum MMP-3 was positively correlated to decrement of ESR and CRP (r=0.397 and 0.474, respectively, P<0.05). The most common adverse events of etanercept included injection site reaction and upper respiratory infection.

CONCLUSIONEtanercept treatment has obvious therapeutic effects on AS without serious adverse effects. MMP-3 may be a potentially useful indicator to assess the effect of anti-TNF-alpha treatment in AS patients.

Adolescent ; Adult ; Antirheumatic Agents ; therapeutic use ; C-Reactive Protein ; metabolism ; Etanercept ; Female ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; blood ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Spondylitis, Ankylosing ; blood ; drug therapy ; pathology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; Young Adult