Full Dose,Reduced Dose And Discontinuation Of Etanercept Biosimilar In Early Axial Spondyloarthritis Patients With Remission Of The Disease

ObjectivesThe study aim was to investigate the effect of etanercept biosimilar(Yisaipu,YSP)dose maintenance,reduction or discontinuation on patients with early axial spondyloarthritis(ax-SpA)who had achieved remission on YSP 50mg weekly and to explore the optimal maintenance treatment stategies in early ax-SpA with remission treated with Yisaipu.MethodsPatients with early ax-SpA with a symptom duration of<3 years who had been treated with YSP 50mg QW for at least 24 weeks and had achieved remission(Ankylosing Spondylitis Disease Activity Scores,ASDAS-CRP<1.3)for more than 12 weeks were identified in Chinese People's Liberation Army General Hospital.Patients who satisfied the criteria entered to one of the following three treatment arms according to the principle of voluntary participation:dose maintenance(YSP50),halving dose(YSP25)and discontinuation(YSPO)for 48 weeks and they were matched 1:1:1 by propensity score matching for baseline data.These data included gender,age,symptom duration,HLA-B27,non-radiographic ax-SpA,smoking status,educational status,financial situation,regular exercise,ASDAS prior to YSP initiation,ASDAS at baseline,BASDAI prior to YSP initiation,BASDAI at baseline,PGA prior to YSP initiation,PGA at baseline,PhGA prior to YSP initiation,PhGA at baseline,CRP prior to YSP initiation,CRP at baseline,time on YSP treatment,and concomitant NSAIDs and/or DMARDs and/or thalidomide therapy.The patients were assessed by the same rheumatologist every 8 weeks for 48 weeks.The primary endpoint of this study was the proportion of non-failure patients between the YSP50,YSP25 and YSPO group.The secondary endpoints included the time from baseline to failure,the proportion of patients regaining remission after flare-up,and number and severity of adverse events.If a flare occurred during the study,the patient was retreated YSP 50mg QW or switch to another TNF blocker.All patients monitored for clinical and laboratory evidence of adverse events(AEs)and serious AEs throughout the study.The continuous data were compared between different groups by analysis of variance.The frequency data were compared using the chi-squared tests.Results(1)A total of 246 patients were screened and were divided into YSP50 group(n=5 8),YSP25 group(n=103)and YSPO group(n=85)according to voluntary principles.Of the 246 patients screened,144 patients entered the study by propensity score matching and each group consisted of 48 patients.No significant differences in various parameters were observed between the three groups after propensity score matching.(2)The proportion of non-failure patients were 91.7%,85.4%,and 72.9%in the YSP50,YSP25,and YSPO group respectively,and the difference of overall recurrence rate was statistically different(p=0.043),whereas the difference between any two of three groups of the multiple comparison(YSP50 vs YSPO group,p=0.032;YSP50 vs YSP25 group,p=0.522;YSP 25 vs YSPO group,p=0.132)were no statistically significant.The median time to flare was no statistically different between in the YSP50(28weeks),YSP25(24weeks)and YSPO(24weeks)group(p=0.242).(3)The majority of patients regained remission rapidly after received YSP 50mg QW or adalimumab 40mg every other week.(4)Infections(including tuberculosis)were more likely to occur in groups treated with YSP,whether YSP50 or YSP25 group,other adverse reactions were similar.(5)The majority of patients in our study were receiving concomitant therapies including DMARDs,NSAIDs,and regular exercise,which may reduce disease flares.(6)Male or smoking patients are prone to replase either in maintaince treatment or discontinuation.Combined with oral medicine,daily execise,early nr-axSpA and long term of YSP treatment are not easy to appear recurrence during the disease maintaince.ConclusionsPatients with early nr-axSpA who were given YSP achieved remission for more than 12 weeks,continuation with YSP at full dose was not obviously superior to halving dose or withdrawal.The sustained disease remission after dose halving or discontinuation of YSP suggests that these two therapeutic strategies can be applied in clinical practice.