Efficacy and Safety of Juan Bi Pill with Add-on Methotrexate in Active Rheumatoid Arthritis:A 48-Week, Multicentre, Randomized, Double-Blind, and Placebo-Controlled Trial

Objective: To explore the efficacy and safety of Juan Bi Pill(JBP) in treatment of active rheumatoid arthritis(RA). Methods: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group(57 cases) and placebo group(58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP(4 g, twice a day, orally) combined with methotrexate(MTX, 10 mg per week) or placebo(4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times(at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times(at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score(DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology(ACR) criteria for 20% and 50% improvement(ACR20/50), Health Assessment Questionnaire Disability Index(HAQ-DI), clinical disease activity index(CDAI), visual analog scale(VAS), Short Form-36(SF-36) score, Medial Outcomes Study(MOS) sleep scale score, serum erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. Results: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment(both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group(both P <0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo(all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups(P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks(ESR and CRP, both P<0.05) or at 12 and 48 weeks(all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment(P=0.75). Conclusion: JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects.(Trial registration: Clinical Trials.gov, No. NCT02885597)