Efficacy And Safety Of Tofacitinib Combined With Methotrexate Or Leflunomide In Patients With Refractory Rheumatoid Arthritis

Objective:To evaluate the efficacy and safety of tofacitinib combined with methotrexate or leflunomide in patients with refractory rheumatoid arthritis.Methods:This was a prospective cohort study.Eligible patients were enrolled in China Yi Bin from March 2020 to February 2021.All patients were treated with tofacitinib combined with methotrexate or leflunomide and were self-controlled before and after administration.The evaluations for efficacy was defined as the mean score change from baseline in Disease Activity Score with 28 joint(DAS28)using erythrocyte sedimentation rate(DAS28-ESR),DAS28-ESR remission rate,mean score change from baseline in Visual Analogue Scale(VAS),physician global assessment of disease activity(PGA),patient global assessment of disease activity(PtGA),clinical disease activity index(CDAI),simplified disease activity index(SDAI)at month 3 and 6,and safety assessments.Results:Actual 80 patients are eligible,but 62 patients were eligible and completed the study(51 were treated with tofacitinib combined with leflunomide,and 11 were treated with tofacitinib combined with methotrexate).The DAS28-ESR mean score at month 3 was significantly altered than the baseline score(6.7±0.14 vs.baseline 3.5±0.16;P<0.0001).The DAS28-ESR remission rate(DAS28 score less than or equal 2.6)was 22.6%(14/62).Pain,PtGA,PGA,CDAI,and SDAI had significant improvements.The upper respiratory infection(6/62,9.7%),pneumonia(1/62,1.6%),urinary tract infection(1/62,1.6%),herpes zoster(2/62,3.2%)and diarrhea(1/62,1.6%)were the main adverse events.Moreover,one patient reported an oncologic event.Laboratory parameters suggested that tofacitinib slightly decreased neutrophils while it increased hemoglobin levels and serum creatinine levels.Logistic regression analysis indicated that old age was significantly associated with RA disease remission(OR=0.21,95%CI[0.06-0.86];P=0.03).Conclusion:Tofacitinib combined with methotrexate or leflunomide in the treatment of refractory RA can rapidly improve the symptoms and signs of patients,reduce RA disease activity,and show good safety.At the same time,aging may be one of the risk factors for reducing the prognosis of RA patients.