Two literature reviews of single-arm open-label (OL), open-label extension (OLE), and epidemiologic studies with a duration of six months or more provide evidence that long-term opioid therapy improves pain scores in chronic non-cancer pain patients.
In an effort to provide evidence on the efficacy and safety of long-term prescription opioid use beyond the standard three-month time frame for the drugs’ clinical trials, researchers from pharmaceutical manufacturer Purdue Pharma LP examined the company’s former clinical studies on its controlled-release opioids and performed a medical literature review of single-arm open-label (OL), open-label extension (OLE), and epidemiologic studies on long-term opioid therapy, as well.
Though only a small subset of patients enrolled in three-month randomized, placebo-controlled trials elect to continue onto OLE studies, the investigators noted that “in real world clinical practice, only 2 percent to 20 percent of patients who start opioid analgesic therapy continue for six months or more, (so) patients who continue in long-term studies may reflect patients who elect to continue opioid analgesic therapy in the real world.”
For their “Long-Term Pain Management with Prescription Opioid Treatment” study on Purdue’s clinical trials, Laura Wallace and her two colleagues analyzed data from 10 chronic non-cancer pain single-arm OL and OLE studies involving a total of 2,687 patients with durations of exposure to Butrans (transdermal buprenorphine), OxyContin (oral oxycodone hydrochloride controlled-release tablet) and Targin (oral oxycodone/naloxone prolonged-release tablet) that ranged from six months to three years.
Tracking the mean change in the chronic non-cancer pain patients’ average pain scores (APS) within each study, the researchers found that mean APS decreases of 46 percent and 50 percent were sustained through week 52 after 12 weeks of Butrans treatment in two OL longitudinal studies conducted in Japan; mean APS reductions ranged from 31 percent to 49 percent at the 12-month mark in four OLE studies on Butrans conducted in the US; the mean APS decrease of 25 percent after 12 weeks of OxyContin therapy remained stable through 52 weeks in one registry study conducted in the US over three years; and mean APS were sustained for one year from the end of double-blind Targin treatment in three OLE studies conducted in Europe.
Additionally, the reductions in APS at week 52 compared to baseline APS “represented a shift in pain level from moderate/severe to mild” in most cases, the study authors wrote. Taking those findings into consideration, the researchers concluded that “these data support the use of controlled-release opioids in the appropriate patients for the long-term management of moderate to severe chronic non-cancer pain.”
Shifting their lens outside of Purdue’s trials, Wallace and three different colleagues found 257 studies on long-term opioid therapy that they discovered via literature searches of major databases, though they ultimately narrowed their review down to 60 studies that met their search criteria of original studies published in English that evaluated a chronic non-cancer pain population, had a duration of at least six months, and examined opioid effectiveness.
According to the authors of “The Long-Term Analgesic Efficacy of Opioid Therapy in Chronic Non-Cancer Pain Patients: A Literature Review of Randomized, Controlled, Open-Label, and Epidemiologic Studies,” 46 studies recorded the percent change in patient pain scores from baseline to the end of the trial, and of those studies, 18 were between six and less than 12 months long, while 28 either hit or extended past the one-year mark. Among the studies that were six to less than 12 months in duration, “15 (83 percent) reported an improvement in pain of greater than or equal to 25 percent from baseline,” and among the studies that continued for one year or more, 23 (82 percent) reported the same pain score improvement, the researchers wrote.
“For all of these studies, a large decrease in reported pain occurred from baseline to three months; thereafter, reported pain decrease was generally maintained through 6 and 12 months, with few studies demonstrating a maintenance of pain scores out to 36 months,” the authors added.
Based on the results from both analyses, Wallace said during PAINWeek’s opening scientific poster session that “although continuing opioid therapy is a decision the physician and patient need to make together, this data gives support to the idea that the drug’s effectiveness will be maintained past a three-month period.”
Both reviews were funded by Purdue.