The aim of this noninferiority study was to investigate clinical effectiveness and safety of buprenorphine transdermal system (BTDS) in patients with moderate to severe musculoskeletal pain inadequately controlled with nonsteroidal anti-inflammatory drugs, compared with sustained-release tramadol tablets.
Eligible patients were randomized (1:1) to receive low-dose 7-day BTDS (5, 10, and 20 μg/h, maximum dosage of 20 μg/h) or sustained-release tramadol tablets (100 mg, maximum dosage of 400 mg/d) over an 8-week double-blind treatment period (3-week titration, 5-week maintenance). The primary endpoint was the difference in the visual analogue scale (VAS) pain scores from baseline to treatment completion. Noninferiority was assumed if the treatment difference on the VAS scale was within ±1.5 cm, this threshold indicating a clinically meaningful result. ClinicalTrials.gov identifier: NCT01476774.
Two hundred eighty patients were randomized to BTDS (n=141) or to tramadol (n=139). Both treatments were associated with a significant reduction in pain by the end of the treatment. The least squares mean difference of the change from baseline in VAS scores between the BTDS and tramadol groups were 0.45 (95% confidence interval, −0.02 to 0.91), which was within the ±1.5 cm predefined threshold, indicating that the effectiveness of BTDS was not inferior to the effectiveness of sustained-release tramadol tablets. The incidence of adverse events was comparable between the 2 treatment groups.
Our results suggest that BTDS is a good therapeutic option for patients experiencing chronic musculoskeletal pain of moderate to severe intensity that is insufficiently controlled by nonsteroidal anti-inflammatory drugs.
*Department of Rheumatology, Peking Union Medical College Hospital
Departments of †Rheumatology
‡Orthopedics, Peking University People’s Hospital
§Department of Rheumatology, Beijing Chao-Yang Hospital
#Department of Medical Statistics, Peking University Clinical Research Institute, Beijing
∥Department of Rheumatology, Sichuan University West China Hospital, Chengdu, Sichuan Province
¶Department of Orthopedics, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
This study was supported by grants from Mundipharma (China) Pharmaceutical Co., Ltd. X.Z. was a principal investigator for this trial. C.Y. and X.Y. work at the department of Medical Statistics, Peking University Clinical Research Institute, and they received payments from Mundipharma (China) Pharmaceutical Co., Ltd to conduct the statistical analyses presented in the present paper and to assist with manuscript preparation. The remaining authors declare no conflict of interest.
Reprints: Xiaofeng Zeng, MD, Department of Rheumatology and Immunology, Peking Union Medical College Hospital (West Campus), Chinese Academy of Medical Sciences, No. 41 Da Mu Cang, Western District, Beijing 100032, China (e-mail: email@example.com).
Received February 24, 2014
Received in revised form July 27, 2014
Accepted July 27, 2014