| ObjectiveTo detect anti-drug antibodies(ADA),Neutralizing Antibodies(NAb)and plasma concentration of Adalimumab(ADL)in the treatment of rheumatoid arthritis(RA)and ankylosing spondylitis(AS)and investigate its value on clinical efficacy.MethodsA total of 78 patients with active RA and 59 patients with active AS from the Rheumatology and immunology Department of the First Affiliated Hospital of Anhui Medical University from September 2020 to September 2022 were recruited.And 30 healthy people from the physical examination center of our hospital during the same period were selected,and sera were collected for quality control.The diagnosis of each RA patient was in line with the RA classification diagnostic criteria revised by ACR in 1987 and the latest RA classification diagnostic criteria proposed by ACR/EULAR in 2010.The diagnosis of each AS patient was in line with the revised New York criteria for AS in 1984.The clinical and laboratory indexes of RA and AS patients were recorded in detail.ADL concentration,ADA and NAb levels were measured by enzyme-linked immunosorbent assay(ELISA).28 joints tenderness/swelling levels were assessed for each RA patient and Disease Activity Score in 28 joints(DAS28)was calculated.DAS28 level combined with morning stiffness time,joint tenderness/swelling degree,inflammatory markers,and antibody levels were used to determine disease activity in RA patients.Ankylosing Spondylitis Disease Activity Score(ASDAScrp),Bath Ankylosing Spondylitis Disease Activity Index(BASDAI),and Spondyloarthritis Research Consortium of Canada(SPARCC)scores were calculated for each AS patient,and combined with morning stiffness time,overall degree of back pain,and inflammatory indicators to determine the disease activity of AS patients.SPSS26.0 statistical software,t test,χ2 test,non-parametric test,correlation and multivariate Logistic regression analysis were used to all the indicators data for statistical analysis.Results① At 24 weeks of treatment,the incidence of ADA in AS group was significantly higher than that in RA group[27.1%(16/59)VS 9.0%(7/78),χ2=7.916,P=0.005].After 12 weeks and 24 weeks of treatment,the incidence of ADA in AS group was also significantly higher than that in RA group[30.5%(18/59)VS 11.5%(9/78),χ2=7.639,P=0.006].The incidence of ADA was 19.7%(27/137)when RA and AS were evaluated together at 12 and 24 weeks of treatment.At 12 and 24 weeks of treatment,ADA positive patients in AS group all were NAb.At 12 weeks of treatment,80%of ADA positive patients in the RA group were NAb and 85.7%were NAb at 24 weeks of treatment.At 12 and 24 weeks of treatment,ADL concentration of AS or RA patients was zero or low level whose ADA was positive.② After 12 weeks and 24 weeks of treatment,ADL concentration in AS patients group with positive ADA was significantly lower than that in ADA negative group(P<0.0001).After 12 weeks of treatment,ADL concentration in RA patients group with positive ADA was obviously lower than that in ADA negative group(P=0.002)and the result was the same after 24 weeks of treatment(P<0.0001).Statistical analysis of patients with AS and RA showed that ADL concentration in ADA positive group was visibly lower than that in ADA negative group after 12 and 24 weeks of treatment(P<0.0001).③ At 24 weeks of treatment,in the RA group,the ADL concentration(at 24 weeks)in the Remission-Low activity group was significantly higher than that in the moderate-severe activity group(P=0.003),and the ADA positive rate(at 24 weeks)was obviously lower than that in the moderate-severe activity group[2.2%(1/46)VS 18.8%(6/32),χ2=4.481,P=0.034].The ADL concentration in RA group with treat-to-target(T2T)was distinctly higher than that in RA group without T2T at 24 weeks(P=0.002)and the ADA positive rate(at 24 weeks)was also clearly lower than that in group without T2T[0%(0/34)VS 15.9%(7/44),72=4.154,P=0.042].④ At 24 weeks of treatment,in the RA group,the ADL concentration at 12 weeks in the Remission-Low activity group was similar to that in the moderate-severe activity group(P=0.539),and the ADA positive rate at 12 weeks was similar,too[8.7%(2/23)VS 17.6%(3/17),χ2=0.132,P=0.717].The ADL concentration at 12 weeks in T2T group was similar to that in group without T2T(P=0.538),and the ADA positive rate at 12 weeks was similar,too[7.1%(1/14)VS 15.4%(4/26),χ2=0.063,P=0.802].⑤ At 24 weeks of treatment in patients with RA,the differences about disease course,age,height,weight,swollen joint count,tender joint count,VAS score,HAQ score,anti-CCP antibody,ESR,RF and ΔDAS28 were similar between groups with ADA positive and ADA negative(P>0.05).Morning stiffness time,CRP and DAS28 in ADA positive group were significantly higher than those in ADA negative group(P<0.05),and BMI was slightly lower(P<0.05).⑥At 24 weeks of treatment,the ADL concentration in RA patients was negatively correlated with DAS28(r=-0.383,P=0.001),morning stiffness time(r=-0.289,P=0.010),ESR(r=-0.376,P=0.001)and CRP(r=-0.398,P<0.0001).The ADA titer was positively correlated with DAS28(r=0.295,P=0.009)and CRP(r=0.238,P=0.037).⑦ At 24 weeks of treatment,in the AS group,the ADL concentration(at 24 weeks)in the Remission-Low activity group was significantly higher than that in the highextreme high activity group(P=0.001),and the ADA positive rate(at 24 weeks)was obviously lower than that in the high-extreme high activity group[22.0%(11/50)VS 71.4%(5/7),χ2=5.184,P=0.023].The ADL concentration(at 24 weeks)in group with T2T was similar to that in group without T2T(P=0.252),and the ADA positive rate(at 24 weeks)was similar,too[21.6%(8/37)VS 40.0%(8/20),χ2=0.893,P=0.345].⑧ At 24 weeks of treatment,in the AS group,the ADL concentration at 12 weeks in the Remission-Low activity group was significantly higher than that in the highextreme high activity group(P<0.0001),and the ADA positive rate at 12 weeks was obviously lower than that in the high-extreme high activity group[22.2%(6/27)VS 100%(4/4),P=0.007].The ADL concentration at 12 weeks in group with T2T was similar to that in group without T2T(P=0.851),and the ADA positive rate at 12 weeks was similar,too[22.2%(4/18)VS 46.2%(6/13),P=0.375].⑨At 24 weeks of treatment in patients with AS,the differences regardingΔASDAScrp score,age,weight,height,disease course,joint function,X-ray staging,occipital wall distance,thoracic dilation,lumbar motion,digital ground distance,BASDAI score,BASFI score and PGA score were the same between ADA positive and ADA negative groups(P>0.05).ASDAScrp score,SPARCC score,BMI,ESR and CRP in ADA positive group were higher than those in ADA negative group(P<0.05).⑩ At 24 weeks of treatment,the ADL concentration in AS patients was negatively correlated with ASDAScrp score(r=-0.444,P=0.001),SPARCC score(r=-0.338,P=0.030),ESR(r=-0.563,P<0.0001),CRP(r=-0.494,P<0.0001)and joint function(r=-0.274,P=0.035),and it was positively correlated with ΔASDAScrp score(r=0.359,P=0.008).The ADA titer was negatively correlated with ΔASDAScrp score(r=-0.336,P=0.021)and positively correlated with ASDAScrp score(r=0.367,P=0.005),SPARCC score(r=0.438,P=0.004),ESR(r=0.561,P<0.0001)and CRP(r=0.444,P<0.0001).(11)Logistic regression analysis(LR Backward)of RA group:Defining DAS28 at 24 weeks of treatment as the dependent variable(0:DAS28<3.2,1:DAS28≥3.2),adjusted for age,sex,and BMI,the result showed that ADA at 24 weeks(OR=11.674,P=0.035,95%CI:1.188-114.696),ADA at 12 and 24 weeks(OR=10.272,P=0.013,95%CI:1.621-65.097)and course(OR=1.072,P=0.034,95%CI:1.005-1.143)were risk factors for RA patients with moderate-severe activity status.(12)Logistic regression analysis(LR Backward)of AS group:Defining ASDAScrp at 24 weeks of treatment as the dependent variable(0:ASDAScrp<2.1,1:ASDAScrp≥2.1),adjusted for age,sex,and BMI,the result showed that ADA at 24 weeks(OR=8.864,P=0.016,95%CI:1.508-52.094),ADA at 12 and 24 weeks(OR=19.000,P=0.009,95%CI:2.075-173.937)and course(OR=1.132,P=0.036,95%CI:1.008-1.271)were risk factors for AS patients with high-extreme high activity status.ConclusionThe total incidence of ADA which almost were NAb in RA and AS patients at 24 weeks after ADL treatment was about 20%.The incidence of ADA in AS patients(30.5%)was significantly higher than that in RA patients(11.5%).ADA was associated with lower plasma concentration and closely related to disease activity in patients with RA and AS. |
