Real-world utilization of once-daily extended-release abuse deterrent formulation of hydrocodone: a comparison with the pre-approval randomized clinical trials.

BACKGROUND AND OBJECTIVE: Hydrocodone bitartrate extended release (Hysingla® ER, HYD) was previously studied in a 12-week randomized, double-blind, placebo-controlled trial and a 52-week open-label safety study. Both of these preapproval studies allowed dose titration to efficacy. The purpose of the present analysis was to compare dosing and utilization patterns in these previous clinical trials with real-world data (RWD) usage in a retrospective claim analysis performed 12-14 months post approval in the US. METHODS: In the claim analysis (Truven Health Analytics MarketScan® Research Database), patients prescribed HYD between January 1, 2015, and April 30, 2016, were followed for up to 6 months of continuous HYD use. Daily average consumption (DACON), initial dose, rescue opioid use and total milligram dose over time were also evaluated. RESULTS: HYD daily dose stabilized at ~60 mg dose once daily across all three studies. There was also a reduced need for rescue medication with HYD, resulting in a lower total opioid milligram dose over time. In the claim analysis, the mean monthly HYD dose increased from 49 to 55 mg in month 2 and then remained stable through month 6. The mean (standard deviation [SD]) time on drug was 79.5 days (61.42 days), and DACON was 1.04 pills/day, corresponding to the approved full prescribing information (FPI) and once-daily dosing. CONCLUSION: In 12-14 months post approval, real-world dosing and utilization of HYD mirrored registration and open-label study findings, with stable once-daily dosing of ~60 mg and no increase in rescue medicine utilization.

Safety and effectiveness of once-daily Hysingla extended-release tablets in patients with baseline depression or anxiety.

AIM: Long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone bitartrate (HYD) for the treatment of moderate to severe noncancer and nonneuropathic pain among patients with and without concurrent depression/anxiety at baseline. MATERIALS & METHODS: Post hoc analysis. RESULTS: HYD demonstrated a safety profile consistent with µ-opioid agonists: Serious adverse events in 12% patients with depression/anxiety including four deaths; 6% without depression/anxiety including one death. All pain scores declined by ≥2 points and mean daily HYD dose remained stable in both subgroups. CONCLUSION: More serious adverse events occurred among patients with comorbid depression/anxiety at baseline than among those without. HYD provided stable and effective analgesia for 52 weeks among chronic pain patients with and without comorbid depression/anxiety at baseline.

Hysingla® ER, a once-daily, single-entity hydrocodone with abuse-deterrent properties in treating chronic nonmalignant and nonneuropathic pain in patients with osteoarthritis.

OBJECTIVES: Osteoarthritis (OA)-related chronic pain is associated with physical and psychosocial impairment as well as poorer quality of life. There is limited literature on long-term opioid therapy in OA patients. This post hoc analysis of OA patients assessed the long-term safety and effectiveness of a once-daily, single-entity, extended-release formulation of hydrocodone (HYD) with abuse-deterrent properties for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which other treatment options are inadequate. METHODS: This is a post hoc analysis of the 307 patients with OA pain from a primary open-label study. Following screening and dose titration, patients who achieved a stable HYD dose continued into a 52-week maintenance period. Supplemental non-opioid or short-acting opioid analgesics were allowed throughout the study. Safety was monitored. Effectiveness evaluations included "average pain over the last 24 hours" scores, "pain right now" scores, Brief Pain Inventory-Short Form and treatment satisfaction questionnaire. RESULTS: No new or unexpected safety concerns emerged during treatment with HYD. HYD demonstrated a safety profile consistent with other µ-opioid agonists with 22% discontinuations of treatment due to adverse events, a majority of which were related to the study drug. Clinically meaningful analgesia was achieved as mean "average pain over the last 24 hours"; scores decreased by 2.9 points from baseline to the end of maintenance. During the maintenance period, pain severity declined 2.7 points and interference by 2.5 points from baseline. Mean "pain right now" scores were similar at dosing and 12 hours later. A majority of patients reported satisfaction with HYD. CONCLUSION: In OA patients, long-term HYD treatment was generally well tolerated and provided clinically important analgesia.

Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

OBJECTIVE: To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. METHODS: This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. RESULTS: Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with µ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. CONCLUSIONS: HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of treatment.

12-Month safety and effectiveness of once-daily hydrocodone tablets formulated with abuse-deterrent properties in patients with moderate to severe chronic pain.

OBJECTIVE: To characterize the long-term safety and effectiveness of Hysingla™ ER, single-entity, once-daily, extended-release hydrocodone bitartrate tablets formulated with abuse-deterrent properties (HYD), offering a new treatment option for appropriate patients with chronic pain. DESIGN: An open-label study with a dose-titration period (up to 45 days) and a maintenance period (12 months). PATIENTS, PARTICIPANTS: A total of 922 patients with chronic nonmalignant and non-neuropathic moderate to severe pain received open-label HYD tablets 20-120 mg; 728 of these achieved a stabilized dose of HYD at the end of dose-titration and entered the maintenance period. RESULTS: The safety profile was similar to that of other oral opioid analgesics, without new or unexpected safety concerns. The most frequent treatment-emergent adverse events (AEs; ≥ 5 percent) were those commonly associated with the use of systemic µ-opioid analgesics, including nausea, constipation, vomiting, fatigue, dizziness, somnolence, and headache. There were 77 (8 percent) patients with a total of 109 nonfatal treatment-emergent serious AEs. Few patients discontinued due to lack of therapeutic effect overall (6 percent), especially during the 12-month maintenance period (4 percent). Pain relief, sleep, functional health, and activities of daily living all improved at the end of the dose-titration period with HYD. These improvements were maintained through the 12-month maintenance period with stable HYD doses and without increase in concomitant supplemental analgesic medications. CONCLUSIONS: This long-term study demonstrated the safety and long-term maintenance of analgesic effect of HYD without continued need for dose increase.