Effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain

Abstract

Background: We examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain.

Methods: This was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment. Patients started with a 5 μg/h buprenorphine patch and were titrated as necessary to a maximum of 40 μg/h over a 6-week period to achieve optimal pain control. Patients continued treatment with the titrated dose for 11 weeks. The primary efficacy endpoint was the change in BS-11 pain scores. Other endpoints included patients' sleep quality and quality of life as assessed by the 8-item Global Sleep Quality Assessment Scale (GSQA) questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire-3 Level version (EQ-5D-3 L), respectively. Tolerability was assessed by collecting adverse events.

Results: A total of 114 eligible patients were included in the analysis. The mean BS-11 score at baseline was 6.2 (SD 1.6). Following initiation of TDB, there was a statistically significant improvement in BS-11 score from baseline to visit 3 (least squares [LS] mean change: -2.27 [95% CI -2.66 to -1.87]), which was maintained till the end of the study (visit 7) (LS mean change: -2.64 [95% -3.05 to -2.23]) (p < 0.0001 for both). The proportion of patients who rated sleep quality as 'good' increased from 14.0% at baseline to 26.9% at visit 6. By visit 6, the mean EQ VAS score increased by 7.7 units (SD 17.9). There were also significant improvements in patients' levels of functioning for all EQ-5D-3 L dimensions from baseline at visit 6 (p < 0.05 for all). Seventy-eight percent of patients reported TEAEs and 22.8% of patients discontinued due to TEAEs. TEAEs were generally mild to moderate in intensity (96.5%).

Conclusions: TDB provides effective pain relief with an acceptable tolerability profile over the 11-week treatment period in Asian patients with chronic musculoskeletal pain. More studies are needed to examine the long-term efficacy and safety of TBD treatment in this patient population.

Trial registration: ClinicalTrials.gov NCT01961271 . Registered 7 October 2013 (retrospectively registered; first patient was enrolled on 28 June 2013 and last patient last visit date was 26 Apr 2015).

Keywords: Asian; Chronic non-malignant pain; Effectiveness; Musculoskeletal; Pain score; Quality of life; Sleep quality; Tolerability; Transdermal buprenorphine.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by local ethics committees (ECs) and was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guideline, the Declaration of Helsinki, and applicable regulatory requirements. All eligible patients were invited to participate in the study. The physicians provided patients with oral and written information describing the nature, purpose, possible risk and benefits of the study. All patients provided written informed consent prior to participation in the study.

The local ECs that approved the study included (i) the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster, Kowloon Central/Kowloon East Cluster Research Ethics Committee, Joint Chinese University of Hong Kong-New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics Committee, and New Territories West (NTW) Cluster & Research Ethics Committee in Hong Kong; (ii) Asan Medical Center Institutional Review Board, Samsung Medical Center Institutional Review Board, Seoul St. Mary’s Hospital Institutional Review Board, Severance Hospital Institutional Review Board, and Seoul National University Hospital Institutional Review Board in Korea; and (iii) Makati Medical Center Institutional Review Board, University of the Philippines Manila Research Ethics Board (UPMREB), St. Luke’s Institutional Ethics Review Committee (SL-IERC), and the University of Santo Tomas Hospital-Institutional Review Board (USTH-IRB).

Consent for publication

Not applicable.

Competing interests

DHY, SIB, SKCC, CKC, YI, HK, CCM, YWM, TKTN, EGP, DAS, and JJL have received research funding from Mundipharma Pte Ltd., Singapore. JJL has also served on the advisory board for Pfizer and Novartis and has been on speaker bureaus for Pfizer, Johnson & Johnson, and Merck Sharp & Dohme. DY is an employee of Mundipharma Pte Ltd., Singapore and HM is a former employee of Mundipharma Pte Ltd., Singapore.

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Figures

Fig. 1

Study design

Fig. 2

Flow of patients through the study

Fig. 3

Change in BS-11 scores from baseline to visit 7 (ITT population)

Fig. 4

Comparison of patients’ levels of functioning for individual EQ-5D-3 L dimensions between baseline and visit 6 (ITT population)