A Long-term Follow-up Study Of Ankylosing Spondylitis Patients After Biological Therapy

BackgroundAnkylosing spondylitis（AS）is a common chronic inflammatory disease.Its pathological characteristics are inflammation,circulatory progressive bone destruction,osteophyte formation,and eventually lead to sacroiliac joint and spinal fusion ankylosis deformity.If the condition is not actively and effectively controlled,the disease can develop to the spine and hip joints in the later stage,eventually leading to permanent disability,which seriously affects the quality of life of patients.With the emergence of tumor necrosis factor inhibitors and their widespread use in clinical practice,the symptoms and signs of patients have been greatly improved,the progress of bone destruction and osteophyte formation has been delayed,and the prognosis of patients has been improved.However,biological agents are expensive,so that the use of most patients is limited after the disease is relieved,while the biological agents are stopped,some patients will relapse and the disease activity will rise again.Studies have confirmed that there is a direct correlation between high disease activity and osteophyte formation and functional impairment.Therefore,follow-up of the disease after remission,timely identification of relapsed patients and intervention,is particularly important to delay bone structural damage,functional damage,and prevent further disability.ObjectiveTo observe the condition in the following 52 weeks of patients with active ankylosing spondylitis treated with human tumor necrosis factor monoclonal antibody for 24 weeks.To explore possible predictors of recurrence with AS patients.MethodsThe patients were enrolled in the Phase Ⅲ clinical trial of the "Clinical Efficacy and Safety Assessment of Active Human Anti-TNF-α Monoclonal Antibody Therapy for AS Patients" in the Southern Hospital in 2017 who met the classification criteria of the 1984 modified New York criteria for AS and in active disease.During the experiment,the fully humanized TNF monoclonal antibody was received 40mg/once,once every 2 weeks,subcutaneously for 12 times.Twenty-six patients were enrolled in the follow-up observation after finishing the experiment and obtaining informed consent.During the follow-up baseline period,specific medication plan information were collected.Disease activity was evaluated at baseline,weeks 13,26,39 and 52 respectively.The primary outcome measure was clinical recurrence,defined as Δ pain≥3,ΔBASDAI≥ 2,and ΔASDAS≥ 0.9.Data analysis using SPSS 22.0 statistical software（SPSS Inc.,Chicago,USA）.ResultsTwenty-six patients with AS were included in the observation,of whom 22 patients with ASAS20 remission,and 4 patients with partial remission of ASAS.The median follow-up time was 61 weeks（interquartile range IQR,57-67 weeks）.At the end of follow-up,AS AS20 remission patients had recurrence in 6 patients,8 patients,and 8 patients with Δ pain≥ 3,ΔBASDAI≥2,and ΔASDAS≥ 0.9,respectively.The median time to recurrence was 38.5 weeks.At 34.9 weeks and 31.6 weeks,recurrence occurred in 28-39 weeks.The recurrence ROC curves of AS patients with various indexes were drawn.The results showed that under the definition of Δ pain≥ 3 recurrence,the AUC values of AS recurrence were predicted by baseline BASMI,ESR and CRP,respectively,0.641,0.521 and 0.667,and the cut-off points were 2.65,10.5 mm/1h and 0.38mg/L respectively,of which BASMI and CRP have a sensitivity of 1 and an ESR sensitivity of 0.33.Under the definition of ΔBASDAI≥ 2 recurrence,the ROC curve of AS recurrence showed that the AUC values of AS recurrence were 0.567,0.509 and 0.563,respectively,and the cut-off points were 2.65,0.27 mg/L and 10.5mm/1h,respectively,using the baseline BASMI,CRP and ESR,The sensitivity was 0.88,1 and 0.25,and the specificities were 0.5,0.21 and 0.93,respectively.Under the definition of ΔASDAS-CRP≥0.9 recurrence,the ROC curve of AS recurrence showed that the AUC values of AS recurrence were 0.522,0.536,0.58,and 0.504,respectively,using the baseline total back pain score,low back pain score,BASMI,and MASES scores.The cut-off points were 48.5 mm,4.85 cm,2.65 and 4,respectively,and the sensitivities were 0.25,0.25,0.75 and 0.125,respectively,and the specificities were 1,0.07,0.43 and 0.07,respectively.Two of the 4 patients who achieved partial relief criteria for ASAS were treated with regular medication.The ASAS20 remission criteria were reached at 14 weeks and 18 weeks of follow-up,and the clinical remission was continued at 52 weeks follow-up.The BASDAI was 0.7 and 2.0,respectively.In the other 2 patients,One patient refused to receive medication,one discontinued on demand,and the BASDAI was 8 and 6 at 52 weeks of follow-up.ConclusionLong-term follow-up of AS patients can help rheumatologists identify high-risk activities or recurrence in a timely manner,which is important for adjusting treatment options.After AS patients’ remission,maintenance of drug therapy can reduce the recurrence rate of AS disease,but the specific maintenance of drug types has an impact on recurrence rate remains to be further studied.Good compliance with treatment can help to improve the symptoms and functions of AS patients.It is important to do a good job in patient education to control the condition of AS.The optimal dosing interval may need to be determined separately during TNFi reduction in AS patients after remission.For patients with relapsed AS who discontinued or reduced TNFi,it is safe and effective to use the TNFi preparation again.Remission of patients with baseline BASMI,CRP,ESR,and low back pain scores had a predictive value for AS recurrence,but further validation is needed.