Abstract:

BACKGROUND: Tumor necrosis factor antagonist (such as, etanercept and adalimumab) is the optimal selection for treating active ankylosing spondylitis. However, these drugs are expensive, so it is urgent to search for a cheap and effective substitute. 
OBJECTIVE: To investigate the 1-year follow-up of recombinant human tumor necrosis factor-α receptor II:IgG Fc fusion protein decrement combined with thalidomide increment in the treatment of active ankylosing spondylitis．
METHODS: The study was approved by the Ethics Committee of the Second People’s Hospital of Yibin. Eighty-six patients of active ankylosing spondylitis were randomly divided into control and combination groups (n=43/group). All patients and their family signed the informed consents. Patients in both groups received subcutaneous injection of etanercept at 25 mg/time. Initial medication was twice/week, for 2 months. When the disease reached the clinical remission standard, the dose of etanercept would be decreased once every 2 months: at the beginning of the third month, we went from twice/week to once/week; at the beginning of the fifth month, it was reduced to once/10 days at the beginning of the seventh month, it was reduced to once/2 weeks. At the beginning of the ninth months, it was reduced to once/3 weeks; at the beginning of the eleventh months, it was reduced to once/4 weeks. After that, no reduction was found until the end of December. If each dose reduction aggravates the disease and does not meet the clinical remission criteria, the previous dose of etanercept should be readjusted. Patients in the combined group were also given thalidomide tablets once a day before bedtime. The initial dose was 25 mg/d, for 2 months. Thereafter, the dose was increased by 25 mg/d every two months until reaching 100 mg/d at the beginning of the seventh month. The duration of treatment was 12 months in both groups.
RESULTS AND CONCLUSION: (1) Forty-three patients in the control group, 38 patients completed the 12-month course of treatment; 43 cases in the combination group, 40 patients completed the 12 months course of treatment. (2) From the end of the fourth month to the end of the twelfth month after treatment, Ankylosing Spondylitis Disease Activity Score-erythrocyte sedimentation rate/C-reactive protein score in the combination group was lower than that in the control group (P < 0.05 or P < 0.01). (3)The Appraisement of Spondyloarthritis International Society 20 compliance rate and Appraisement of Spondyloarthritis International Society 5/6 compliance rate of the combination group were higher than those of the control group (P < 0.05 or P < 0.01). (4) The clinical remission maintenance rate in the combination group was higher than that in the control group (χ2=8.527, P=0.003). (5) The total drug dosage of etanercept of each patient in the combination group was lower than that in the control group within 12 months (t=2.932, P=0.004). (6) There was no significant difference in the incidence of adverse reactions between two groups (χ2=0.174, P=0.677). (7) These results indicate that for the 12-month treatment of ankylosing spondylitis, in the scheme of prolonging the interval between the drugs of etanercept, a higher remission rate or a lower disease activity can be achieved, and the combination of thalidomide and isopropyl does not increase the adverse reactions of the drugs.

Key words: ankylosing spondylitis, recombinant human tumor necrosis factor-alpha receptor II:IgG Fc fusion protein, thalidomide, tumor necrosis factor