A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Abstract

Abstract Background: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-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 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. Methods: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n\u200a=\u200a59) vs. MTX (n\u200a=\u200a59) alone or 99Tc-MDP (n\u200a=\u200a59) 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\u200a+\u200a99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P\u200a=\u200a0.03 for MTX\u200a+\u200a99Tc-MDP vs. MTX, and MTX\u200a+\u200a99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX\u200a+\u200a99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48\u200aweeks (MTX\u200a+\u200a99Tc-MDP vs. MTX: P\u200a=\u200a0.03, 99Tc-MDP vs. MTX: P\u200a=\u200a0.03, 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 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. Trial Registration: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.