A Double-Blind, Double-Dummy, Randomized Controlled, Multicenter Trial Of Tc-99-Methylene Diphosphonate In Patients With Moderate To Severe Rheumatoid Arthritis

Background: Clinical observational studies revealed that Tc-99-methylene diphosphonate (Tc-99-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of Tc-99-MDP plus methotrexate (MTX) vs. MTX alone or Tc-99-MDP alone on disease activity and structural damage in MTX-naive Chinese patients with moderate to severe RA.Methods: Eligible patients with moderate to severely active RA were randomized to receive Tc-99-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or Tc-99-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.Results: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + Tc-99-MDP combination group (69.5%) than that in the MTX group (50.8%) or Tc-99-MDP group (47.5%) (P = 0.03 for MTX + Tc-99-MDP vs. MTX, and MTX + Tc-99-MDP vs.Tc-99-MDP, respectively). The participants in the MTX + Tc-99-MDP group and the Tc-99-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + Tc-99-MDP vs. MTX: P = 0.03, Tc-99-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.Conclusions: This study demonstrated that the combination of Tc-99-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and Tc-99-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of Tc-99-MDP therapy in patients with RA are warranted.