Clinical Study Of Different Doses Glucocorticoid In Refractory Ankylosing Spondylitis

Objective:To assess the clinical efficacy and safety of different doses glucocorticoid in on-steroidal anti-inflammatory drug-refractory ankylosing spondylitis.Methods:This was an open-labeled clinical trial for 16 weeks.48 cases of AS were Included in the study. They were in line with the revised New York standard of 1984 and were in active stage. After taking at least 2 different types of NSAIDs for at least 2 months, ESR, CRP, and BASDAI had not significant improvement as compared with the baseline, which is called NSAIDs refractory AS. The selected patients were randomly divided into 2 groups of high-dose group and low-dose group. High-dose group of 27 patients were given methylprednisolone (MP) 250～500mg/d, intravenous for 3 to 4 days per week, treatment 3 times, then given prednisone 20mg per day to maintain for 3 weeks. At the 6th week, prednisone was reduced to 15mg/d, then gradually was reduced by 2.5mg per week to 7.5mg. Then we need 7 weeks to reduce 7.5mg to zero. Finally we removed the prednisone after 16 weeks. Low-dose group of 21 patients were given prednisone 20mg per day to maintain. At the 6th week, prednisone was reduced to 15mg/d. Then the reduction principle was the same. The two groups continued to give DMARDs. We assessed the efficacy and safety of the two groups. The recurrence of the patients was followed up to the 16th week.In this study, we assessed the efficacy with internationally recognized indicators, which included ASAS20, ASAS40, VAS, BASDAI, BASFI, ESR, CRP. We got safety assessment by collecting adverse events. The time point of evaluation was zero, first, second, third, sixth week.Results:1.Efficacy Results:(1)At week 1,74.1% of patients reached the primary end point of ASAS20. The percent of patients reaching the secondary endpoints of ASAS40 was 33.3% in the high-dose group. The percent of patients reaching ASAS20 and ASAS40 were 14.3% and 0% respectively in the low-dose group. The improvements of BASDAI, BASFI, ESR, CRP of the high-dose group were more statistically significant than the low-dose group. The differences were statistically significant (p<0.05)(2) At week 6,81.5% of patients reached the primary end point of ASAS20. The percent of patients reaching the secondary endpoints of ASAS40 was 77.8% in the high-dose group. The percent of patients reaching ASAS20 and ASAS40 were 42.9% and 28.6% respectively in the low-dose group. The improvements of BASDAI, BASFI, ESR, CRP of the high-dose group were more statistically significant than the low-dose group. The differences were statistically significant (p<0.05).2. Safety Results:In high-dose group,10 patients occurred side effects with treatment-related. The most common was the impact on blood glucose and the infection of upper respiratory and digestive tract, then the damage of skin and its subsidiary organ. Most drug-related adverse effects were mild and the symptoms could alleviate after drug withdrawal and symptomatic treatment. In low-dose group 3 patients occurred treatment-related adverse drug reactions. Difference was not statistically significant (p=0.078).3. Follow Up Study Results:24 patients who achieved ASAS20 after the last MP treatment in the high-dose group and 9 patients who achieved ASAS20 after 6 weeks in low-dose group were followed using a definition of relapse of BASDAI reaching 3.5 or were followed up to the 16th week when hormone completely removed.2 cases were lost to follow in high-dose group. No case was lost to follow in low-dose group. The remaining patients continued using DMARDs. Recurrence rates were 9.09% and 11.1% respectively at 9th week in high-dose group and in low-dose group (P=0.863). Recurrence rates were 18.2% and 22.2% respectively at 12th week in high-dose group and in low-dose group (P=0.796). Recurrence rates were 18.2% and 33.3% respectively at 16th week in high-dose group and in low-dose group (P= 0.360).Conclusions:1. Short-term low-dose of 20mg GCs can release symptoms, signs and inflammatory indicators in AS, it can be considered as a new approach while exiting contraindication of the MP pulse therapy and poor economic conditions.2. The improvement of symptoms, signs and inflammatory indicators with MP pulse therapy were better than low-dose oral hormone in AS. Although there is no statistically significant difference on adverse reactions, long-term side effects of the MP pulse therapy still need more big samples, multi-center clinical studies to assess.