Factors affecting acceptability of titrated oxymorphone extended release in chronic low back pain – an individual patient analysis

Abstract

Objective:

To evaluate the influence of age, sex, and previous opioid experience on the likelihood of successfully titrating opioid-naive and experienced patients with chronic low back pain (CLBP) to an effective and well-tolerated dose of oxymorphone extended release (ER).

Methods:

Post hoc analysis of open-label titration phases of two enriched-enrollment randomized-withdrawal phase III trials in 575 adults with moderate-to-severe CLBP. Opioid-naive patients (n = 325) initiated oxymorphone ER at 10 mg/day (5 mg q12 h). Opioid-experienced patients (n = 250) initiated at a dose equianalgesic to their previous opioid and were allowed doses of 5 mg oxymorphone immediate-release rescue medication every 4–6 h, as needed. Oxymorphone ER was gradually titrated to a dose that reduced pain to ≤40 mm on a 100 mm visual analog scale.

Clinical trial registration:

NCT00225797, NCT00226421.

Main outcome measures:

Number of patients reaching stabilized oxymorphone ER dose, reasons for treatment discontinuation in patients not reaching stabilized dose.

Results:

Open-label titration was successful in 61% (348/575) of patients, and similar proportions of men (63%) and women (59%) and opioid-naive (63%) and experienced (57%) patients. Patients aged ≥65 years were less likely than patients aged <65 years to complete titration (45 vs. 63%; p = 0.002; 95% CI, −0.30 to −0.06) and more likely to discontinue owing to adverse events (40 vs. 15%; p < 0.001; 95% CI, 0.14–0.36). Oxycodone-experienced patients were less likely than hydrocodone-experienced patients to complete titration (46 vs. 62%, p = 0.03; 95% CI,−0.30 to −0.02). Among successfully titrated patients, pain decreased regardless of prior opioid therapy, sex, or age.

Conclusions:

Most patients with CLBP were titrated to an effective, generally well-tolerated oxymorphone ER dose. Older patients and those converted from oxycodone may require more gradual titration. A study limitation is that patients initiated oxymorphone ER to comply with protocol, whereas treatment failure typically motivates opioid initiation or switching in clinical practice.

Key words:

• Analgesics
• Factors, age
• Gerontology
• Low back pain
• Opioid
• Oxymorphone
• Sex factors

Transparency

Declaration of funding

Endo Pharmaceuticals Inc., Chadds Ford, PA, sponsored the two studies analyzed in this report and contributed financial and statistical support to the development of this publication. All coauthors contributed to the interpretation of the data, participated in the development and review of the manuscript, and gave final approval of the manuscript for submission.

Declaration of financial/other relationships

J.H.P. was an investigator on the two studies and has no financial conflicts of interest to declare. E.M.G. and Q.X. have declared that they are employees of Endo Pharmaceuticals Inc. Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has declared that he/she has acted as a consultant to Mundipharm. Peer Reviewer 2 has disclosed no relevant financial relationships.

Acknowledgments

The authors would like to thank Suna Barlas, PhD, of Endo Pharmaceuticals Inc. for her statistical support. The authors would also like to thank Jeffrey Coleman, MA, of Complete Healthcare Communications, Inc., Chadds Ford, PA, who provided medical writing and editorial support for this article, which was funded by Endo Pharmaceuticals Inc.

The data presented herein were presented in part at PAINWeek 2009, Las Vegas, NV, September 9–12, 2009; American Academy of Physical Medicine and Rehabilitation 70th Annual Assembly and Technical Exhibition, Austin, TX, October 22–25, 2009.