Leflunomide For The Inductive And Maintenance Treatments Of IgG4-related Diseases-A Retrospective Case-control Study

Objective:To determine the efficacy and safety of leflunomide(LEF)in induced remission and maintenance therapy of immunoglobulin G4-related diseases(Ig G4-RD),to provide new ideas for clinical treatment of Ig G4-RD in the future,to further optimize the treatment of Ig G4-RD,and to provide a basis for the future research of Ig G4-RD.Methods:This study is a case-control study,which retrospectively included Ig G4-RD patients who were treated in the affiliated Hospital of Qingdao University from January2013 to October 2020 and have been followed up for 12 months.All the patients were in the active stage of the disease when they entered the study.Patients who were treated with glucocorticoid(GC)combined with LEF(LEF group)were selected as case group.After matching age,sex composition,course of disease,number of involved organs,Ig G4-RD response index(RI)and related laboratory indexes at the beginning of treatment,those who were only treated with GC(monotherapy group)and those treated with GC combined with alternative immunosuppressants(alternative group)were selected as control groups.Patients with benign and malignant tumors and acute and chronic infectious diseases were excluded.The general data,allergic history and involved organs of all subjects were collected,and the clinical manifestations and specific treatment information of each subject were recorded in detail.The laboratory examination and imaging examination information of all subjects at 0,1,3,6,12 months were collected by His system.Laboratory examination included C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),eosinophil(Eo)count,immunoglobulin G4(Ig G4),immunoglobulin G(Ig G)and immunoglobulin E(Ig E).Imaging examination included nuclear magnetic resonance imaging,CT imaging and color Doppler ultrasound imaging.In addition,the histopathological results and changes of the patients in three groups were recorded in detail.The Ig G4-RD disease response index(Ig G4-RD RI)was calculated at each follow-up time point,and the disease activity,remission and recurrence were judged by the absolute value and difference of Ig G4-RD RI.The disease remission rate,cumulative recurrence rate within 12 months and GC doses of different treatment schemes were compared.Results:A total of 84 patients were included in the study,including 15 patients in LEF roup,23 patients in monotherapy group,46 patients in alternative group.There was no significant difference in age,sex composition,initial course of disease,number of involved organs,Ig G4-RD RI,CRP,ESR,Eo and other laboratory indexes between the case group and the control groups(P>0.05).The decrease of Ig G4-RD RI in the three groups was more than 50%after 12 months of treatment,and the Ig G4-RD RI of the LEF group was significantly better than that of the monotherapy group at 3,6 and 12 months of treatment(P<0.05),but there was no significant difference between the LEF groups and the alternative groups(P>0.05).At 6 and 12 months after treatment,the disease remission rate in the LEF group(66.7%and 86.7%)was significantly higher than that in the monotherapy group(17.4%and 43.5%)(P<0.05),but there was no significant difference compared with alternative groups(52.2%and 76.1%)(P>0.05).During the12-month follow-up,the cumulative recurrence rate in the LEF group was significantly lower than that in the monotherapy group(13.3%vs 47.8%,c~2=4.799,P=0.039),and the cumulative GC dose(4215.0±1068.3)was also significantly lower than that in the monotherapy group(7383.3±2691.8)(t=4.325,P<0.01),but neither of them were different from those of the alternative group(cumulative recurrence rate 23.9%,cumulative GC dose 5429.4±2197.5)(P>0.05).At 3,6 and 12 months of follow-up,the daily dose of GC in LEF group was lower than that in monotherapy group and alternative group(P<0.05).A total of 8 adverse events were observed,including 2 cases in LEF group and 6 cases in alternative group,which were reversible after drug withdrawal or symptomatic support treatment,but no serious adverse events were observed.Conclusions:LEF has certain efficacy and safety in the induced remission and maintenance treatment of Ig G4-RD;the efficacy of GC combined with LEF is better than that of GC alone;compared with GC combined with alternative immunosuppressants,LEF combined therapy is similar in efficacy and safety,but the daily dosage of GC is less.