(770): Management of breakthrough pain (BTP) in opioid-tolerant patients with chronic low back pain or neuropathic pain: Combined analysis of two randomized, double-blind studies of fentanyl buccal tablet (FBT)

Abstract

Short-acting opioids are recommended for breakthrough pain (BTP) associated with chronic cancer pain, and have been used similarly for episodic exacerbations of severe pain in patients with chronic noncancer pain. BTP typically reaches peak intensity before the onset of analgesia with traditional short-acting opioids, creating a need for agents with a rapid onset of action. FBT is intended to provide this by enhancing transbuccal absorption of fentanyl. This abstract presents an exploratory analysis of data from two randomized, placebo-controlled, double-blind studies of FBT, one in opioid-tolerant patients with chronic neuropathic pain, one in chronic low back pain. A meta-analysis approach was used to combine the data: each study was weighted by the inverse variances determined at each timepoint. Studies had identical designs: patients identifying an effective FBT dose (100-800μg) during a titration phase entered a double-blind phase (n=156/164) to treat 9 BTP episodes. Pain intensity (PI) was measured on an 11-point scale; PI differences (PIDs) between each timepoint and pretreatment were calculated. The primary efficacy measure was the time-weighted sum of PID scores for the first 60 minutes (SPID60). SPID60 significantly favored FBT vs placebo (LSM±SE: 8.96±0.25 vs 4.66±0.43; 95% CI for difference vs placebo: 3.32, 5.26). A significant effect of FBT vs placebo in PID was apparent at 10 minutes (0.58±0.04 vs 0.39±0.07; 95% CI: 0.04, 0.34) and was sustained throughout the observation period (2 hr: 3.43±0.09 vs 1.66±0.15; 95% CI: 1.45, 2.11). The proportion of BTP episodes with ≥33% improvement in PI favored FBT at 10 minutes (9% FBT vs 5% placebo); differential effects increased as time progressed (21% vs 12%, 15 minutes; 44% vs 20%, 30 minutes). In summary, FBT had an early onset of action and was effective for treating BTP in a combined population of opioid-tolerant patients with chronic low back or neuropathic pain. Short-acting opioids are recommended for breakthrough pain (BTP) associated with chronic cancer pain, and have been used similarly for episodic exacerbations of severe pain in patients with chronic noncancer pain. BTP typically reaches peak intensity before the onset of analgesia with traditional short-acting opioids, creating a need for agents with a rapid onset of action. FBT is intended to provide this by enhancing transbuccal absorption of fentanyl. This abstract presents an exploratory analysis of data from two randomized, placebo-controlled, double-blind studies of FBT, one in opioid-tolerant patients with chronic neuropathic pain, one in chronic low back pain. A meta-analysis approach was used to combine the data: each study was weighted by the inverse variances determined at each timepoint. Studies had identical designs: patients identifying an effective FBT dose (100-800μg) during a titration phase entered a double-blind phase (n=156/164) to treat 9 BTP episodes. Pain intensity (PI) was measured on an 11-point scale; PI differences (PIDs) between each timepoint and pretreatment were calculated. The primary efficacy measure was the time-weighted sum of PID scores for the first 60 minutes (SPID60). SPID60 significantly favored FBT vs placebo (LSM±SE: 8.96±0.25 vs 4.66±0.43; 95% CI for difference vs placebo: 3.32, 5.26). A significant effect of FBT vs placebo in PID was apparent at 10 minutes (0.58±0.04 vs 0.39±0.07; 95% CI: 0.04, 0.34) and was sustained throughout the observation period (2 hr: 3.43±0.09 vs 1.66±0.15; 95% CI: 1.45, 2.11). The proportion of BTP episodes with ≥33% improvement in PI favored FBT at 10 minutes (9% FBT vs 5% placebo); differential effects increased as time progressed (21% vs 12%, 15 minutes; 44% vs 20%, 30 minutes). In summary, FBT had an early onset of action and was effective for treating BTP in a combined population of opioid-tolerant patients with chronic low back or neuropathic pain.