[A randomized, single-blind, parallel, controlled clinical study on single intra-articular injection of etanercept in treatment of inflammatory knee arthritis].

OBJECTIVE: To evaluate the efficacy and safety of single intra-articular etanercept injection in patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) who had knee arthritis. METHODS: This was a randomized, single-blind, parallel, controlled clinical trial. The subjects were the RA or SpA patients with the knee arthritis without deformity, moderate or severe bone erosion and obvious joint space narrowing in radiography in the target knees, who had taken at least 6-week therapy with routine dosage of disease modifying anti-rheumatic drugs (DMARDs) before the study. The subjects were randomized in 2:1 ratio to receive either single intra-articular 25 mg etanercept injection or 2 ml compound betamethasone to the target knees joint after their synovial fluid being drawn away at baseline. They were followed up four weeks after injection. The primary end-point was the 4-week change in the modified Hospital for Special Surgery (HSS) knee score for the target knee. RESULTS: Forty-seven subjects in the experimental group and twenty-three subjects in the controlled group were included in the trial. The modified HSS knee score for the experimental group was baseline mean 65.6 ± 14.0, follow-up 84.3 ± 11.1 (P < 0.0001), the controlled group baseline mean 68.2 ± 11.4, follow-up 79.4 ± 15.5 (P = 0.0015). A mean (34.9 ± 38.9)% improvement on the modified HSS knee score was achieved in the experimental group, while (17.9 ± 24.5)% improvement on the modified HSS knee score was achieved in the controlled group (P = 0.0467). Adverse events were observed in eight patients (19.0%) in the experimental group and eight patients (44.4%) in the controlled group. No serious adverse event had been observed. CONCLUSIONS: Single intra-articular 25 mg etanercept injection had a better efficacy than 2 ml compound betamethasone. It was an effective and safe therapeutic option for SpA and RA patients who had knee arthritis without obvious change in radiography.

Evaluation of efficacy and safety of diacerein in knee osteoarthritis in Chinese patients.

OBJECTIVE: To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). METHODS: A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. RESULTS: Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians' overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P > 0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P < 0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P < 0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P < 0. 001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. CONCLUSIONS: Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.

[A short-term efficacy and safety study of infliximab in active ankylosing spondylitis].

OBJECTIVE: To evaluate the efficacy and safety profile of a loading regimen of the anti-TNFalpha antibody infliximab in ankylosing spondylitis (AS). METHODS: This was an open-labeled trial. Subjects eligible for this study were adults with a diagnosis of definite AS. Active disease was a Bath AS disease activity index (BASDAI) > or = 4 and spinal pain VAS > or = 4. Concurrent stable treatment with nonsteroidal anti-inflammatory drugs was permitted during the study. Subjects were not permitted to be on methotrexate, systemic corticosteroids, cytotoxic drugs or disease-modifying anti-rheumatic drugs for various time periods before screening. Infliximab 5 mg/kg was infused at weeks 0, 2, 6. All patients were followed up to 10 weeks. The primary endpoint was proportion of ASAS 20 responders at week 10. The secondary endpoints were the proportion of subjects achieving an ASAS partial remission, the change from baseline in bath AS functional index and in the physical component summary score of the short form-36 in health survey questionnaire at week 10. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated. RESULTS: 63 patients (79% males, 90% HLA-B(27)(+), median age 32 yr, median disease duration 10 yr) completed the treatment. The proportion of ASAS 20 responders at 2, 6, 10 week was 75%, 84%, 84% respectively. The proportion of ASAS partial remission patients at 2, 6, 10 week was 10%, 21%, 30% respectively. Results for other secondary efficacy endpoints showed that infliximab could provide substantial benefits to patients with AS by reducing clinical signs and symptoms and improving range of motion, physical function, and quality of life. Sixty-five percent of subjects reported treatment-related adverse events. The most frequently occurred were upper respiratory tract infection and skin and appendages. Secondary was elevation of liver enzymes. Most treatment-related adverse events were mild to moderate in severity. Two patients had serious dermatitis and one stopped treatment owing to an infusion reaction. Short-term follow up indicated that effect of Remicade lasted for about 2 to 8 months without any new side effect. CONCLUSION: A loading regimen of infliximab demonstrated consistent evidence of efficacy and was well tolerated in the treatment of active AS.

[Effects of infliximab and etanercept, two types of anti-tumor necrosis factor-alpha inhibitor on serum level of matrix metalloproteinase 3 expression in patients with ankylosing spondylitis].

OBJECTIVE: To evaluate the effect of Infliximab and Etanercept two types of anti-tumor necrosis factor-alpha (TNF-alpha) inhibitors, on the serum level of matrix metalloproteinase 3 (MMP-3) in the pathogenesis of ankylosing spondylitis (AS). METHOD: 47 patients with AS, 40 males and 7 females, aged 17 - 51, were treated with Infliximab (5 mg/kg i.v at weeks 0, 2, and 6); and 26 patients with AS were treated with Etanercept (25 mg, twice a week for 12 weeks). Clinical data including Bath AS indices (BASDAI and BASFI) and sera were collected at baseline and other different times. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. Serum levels of MMP-3 were measured with MMP-3 ELISA kits. RESULTS: Two, six, and ten weeks after Infliximab treatment the levels of ESR, CRP, and serum MMP-3 of the AS patients were all significantly lower than the baseline level (all P < 0.01), and the serum MMP-3 levels were all significantly correlated with ESR (all P < 0.05). In the Etanercept group 1, 2, 4, 8, and 12 weeks after treatment the levels of serum MMP-3, ESR, CRP, BASDAI, and BASFI were all significantly lower than the baseline levels (all P < 0.01); before the treatment ESR was significantly correlated with CRP (r = 0.80, P < 0.01), BASDAI was significantly correlated with BASFI (r = 0.48, P < 0.05), and MMP-3 was significantly correlated with ESR (r = 0.74, P < 0.01) and with CRP (r = 0.72, P < 0.01); and 12 weeks after the treatment significant correlation still existed between ESR and CRP (r = 0.40, P < 0.05), BASDAI and BASFI (r = 0.89, P < 0.01), and MMP-3 and ESR (r = 0.43, P = 0.029), however, there was no significant correlation between CRP and serum level of MMP-3 (r = 0.37, P = 0.061). CONCLUSION: Infliximab and Etanercept, 2 anti-TNF-alpha inhibitors, not only significantly decrease the ESR and CRP, but also decrease the serum level of MMP-3 of patients with AS. MMP-3 is involved in the pathogenesis and disease activity of AS. MMP-3 is also a potentially useful marker of AS disease activity and useful parameter to assess the effectiveness of anti-TNF-alpha inhibitor in treatment of AS.