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To investigate the effect of inflammation on expressions of bone morphogenetic proteins (BMPs) in peripheral blood mononuclear cells (PBMCs) and its association with individual radiographic changes in patients with ankylosing spondylitis (AS).The changes in BMP-2, -4, and -7 gene expressions in PBMCs were measured after stimulation by tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The correlation of increase in gene expression with clinical and radiographic findings in patients with AS were analyzed.Both TNF-α and IL-1β could enhance BMP-2 expression in PBMCs from AS patients. Increases in BMP-2, -4, and -7 expressions in PBMCs positively correlated with total modified Stoke Ankylosing Spondylitis Spinal Score (all p0.05). Moreover, increases in BMP-2, -4, and -7 gene expressions after TNF-α and IL-1β stimulation were greater among AS patients with versus without severe sacroiliitis (all p0.05). Increases in BMP-2 and -7 expressions were greater in PBMCs from 4 patients with total (cervical, thoracic, and lumbar) spinal ankylosis than in the 8 patients who did not have total spinal ankylosis (all p0.05).In AS, inflammation upregulates the expression of BMPs in PBMCs which may lead to the radiographic progression with new bone formation.

Over a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25 mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behcet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behcet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behcet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (

Tumor necrosis factor-alpha (TNF-α) inhibitors including etanercept have been demonstrated to be very effective in severe ankylosing spondylitis (AS) in Caucasian patients. However, clinical efficacy of etanercept to treat active AS in Chinese patients has not been reported. In this study, a prospective, open-label trial of etanercept (25 mg BIW), involving 46 AS patients from 16 medical centers of Taiwan, was conducted. Questionnaire was utilized to record demographic data and clinical parameters, including Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Assessment in Ankylosing Spondylitis (ASAS) 20, 50, and 70, and others, before and at different time intervals after etanercept treatment. Laboratory tests including blood chemistry, hematology, urine analysis, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were done at baseline and at weeks 4, 8, and 12. In this 12-week study, etanercept demonstrated rapid and significant improvement in the ASAS20 response criteria (91.3%), at as early as 2 weeks of therapy (71.3%). Partial remission of AS was achieved in 49.3% of patients after 12 weeks of treatment. Disease activity (BASDAI) and function (BASFI) were also significantly improved after 12 weeks etanercept treatment (p < 0.0001 and p < 0.0001, respectively). In addition, significant increase of chest expansion (2.77 ± 1.69 cm versus 3.56 ± 1.82 cm, p = 0.0004) and lumbar flexion (2.11 ± 2.76 cm versus 2.58 ± 3.42 cm, p = 0.0075) and significant reduction of occiput-to-wall distance (6.59 ± 7.14 cm versus 5.32 ± 6.65 cm, p = 0.0006) were also demonstrated. Both ESR and CRP declined significantly after patients were treated with etanercept. There were no severe adverse effects during the treatment period. Etanercept is generally safe, well tolerated, and effective in Chinese patients with severe AS. Clinical efficacy, including partial remission and BASDAI, is even better in Chinese than in Caucasian patients. Further study is required to assess long-term efficacy and safety in Chinese patients with AS.