Kaur Aman Deep, McQueen Angela, Jan Saira
Novo Nordisk Inc., 100 College Rd. West, Princeton, NJ 08540, USA.
J Manag Care Pharm. 2008 Mar;14(2):186-94. doi: 10.18553/jmcp.2008.14.2.186.
Management of opioid dependence is associated with many challenges such as the misuse of prescribed treatment and lack of medication adherence that can affect the clinical outcome of the patient. Buprenorphine-naloxone was approved by the U.S. Food and Drug Administration in October 2002 as the first outpatient treatment indicated for opioid dependence. There is only 1 report in the literature on the effectiveness of buprenorphine-naloxone in a real-world setting and no reports on persistence and cost obtained from administrative claims data.
To determine (1) the length and cost of therapy with oral buprenorphine-naloxone, and (2) the cost avoidance for opioid dependence as measured by opioid utilization and opioid drug cost obtained from pharmacy claim records.
The patients for this drug use evaluation (DUE) were identified from a New Jersey managed care organization (MCO) with approximately 1.8 million members with pharmacy benefits who (a) were continuously enrolled from October 1, 2004, through September 30, 2006; (b) had their first buprenorphine-naloxone pharmacy claim during the fixed 6-month initiation period (April 1, 2005, through September 30, 2005); and (c) had at least 1 opioid pharmacy claim in the 6-month pre period preceding the 6-month initiation period. The outcome measures included the number of opioid pharmacy claims, daily dose, days supply, and cost defined as opioid ingredient cost. Member cost share and net plan cost (after subtraction of member cost share) were also measured. The measurement periods for opioid use and cost were the fixed calendar periods for 6 months from October 1, 2004, through March 31, 2005, and for 12 months from October 1, 2005, through September 30, 2006. Persistence in the 12-month follow-up period was defined as a gap of 30 days or less between depletion of the days supply for the preceding pharmacy claim for buprenorphinenaloxone and the date of service (refill date) for the succeeding pharmacy claim for buprenorphine-naloxone.
Of the 160 new buprenorphine-naloxone users with continuous pharmacy enrollment for the 2-year period ending September 30, 2006, 84 patients (52.5%) had at least 1 opioid pharmacy claim in the 6-month pre period from October 1, 2004, through March 31, 2005, and were included in this DUE. In the 12-month post period from October 1, 2005, through September 2006, the median length of therapy with buprenorphinenaloxone was 1 month, and the mean length of therapy was 3.5 months. Only 40 patients (47.6%) had a pharmacy claim for buprenorphine-naloxone at month 1 in the 12-month post period. Persistence was 27.4% (n = 23) at 6 months (March 2006) and 20.2% (n = 17) at 12 months (September 2006) in the post period. A total of 24 study patients (28.6%) had no opioid pharmacy claims other than buprenorphine-naloxone in the 12-month post period. Utilization of opioids decreased by 18.8%, from 1.49 opioid pharmacy claims per patient per month (PPPM) in the pre period to 1.21 claims PPPM in the post period (P = 0.031). Excluding the 0.42 buprenorphine-naloxone claims PPPM, opioid utilization decreased by 47.0%, from 1.49 claims PPPM to 0.79 claims PPPM (P < 0.001) in the 12-month post period. Before subtraction of member cost share, the actual drug cost of opioids including buprenorphine-naloxone appeared to be 26.9% lower ($156.24 PPPM) in the post period compared with $213.74 PPPM in the pre period, but the difference was not statistically significant (P = 0.254). Excluding the cost of the buprenorphine-naloxone, actual opioid drug cost decreased 66.5% from $213.74 PPPM pre period to $71.65 PPPM post period (P = 0.047).
Approximately one half of the patients who had a new claim for buprenorphine-naloxone were excluded from this study because there was no utilization of prescription opioids in the 6 months prior to initiation. For patients with documented use of prescription opioids prior to initiation, treatment with buprenorphine-naloxone was associated with a reduction in opioid utilization and cost in the first year of follow-up. Persistence was only 27% at 6 months and 20% at 12 months, and there were no drug cost savings in the follow-up period when the actual cost of the buprenorphine-naloxone therapy was included.
阿片类药物依赖的管理面临诸多挑战，如处方治疗的滥用以及患者缺乏药物依从性，这些都会影响患者的临床治疗结果。丁丙诺啡 - 纳洛酮于2002年10月被美国食品药品监督管理局批准，成为首个用于阿片类药物依赖的门诊治疗药物。文献中仅有1篇关于丁丙诺啡 - 纳洛酮在实际应用中的有效性报告，且尚无从行政索赔数据得出的关于持续用药情况和成本的报告。
确定（1）口服丁丙诺啡 - 纳洛酮的治疗时长和成本，以及（2）通过药房索赔记录中的阿片类药物使用情况和阿片类药物成本来衡量阿片类药物依赖的成本节约情况。
本药物使用评估（DUE）的患者来自新泽西州一家管理式医疗组织（MCO），该组织约有180万拥有药房福利的成员，这些成员需满足以下条件：（a）在2004年10月1日至2006年9月30日期间持续参保；（b）在固定的6个月起始期（2005年4月1日至2005年9月30日）内首次有丁丙诺啡 - 纳洛酮的药房索赔记录；（c）在6个月起始期之前的6个月预期间至少有1次阿片类药物的药房索赔记录。观察指标包括阿片类药物的药房索赔次数、每日剂量、供应天数以及定义为阿片类药物成分成本的费用。还测量了成员成本分担和净计划成本（扣除成员成本分担后）。阿片类药物使用和成本的测量期为固定的日历时间段，2004年10月1日至2005年3月31日为6个月，2005年10月1日至2006年9月30日为12个月。12个月随访期内的持续用药定义为前一次丁丙诺啡 - 纳洛酮药房索赔的供应天数耗尽与后一次丁丙诺啡 - 纳洛酮药房索赔的服务日期（ refill date）之间的间隔为30天或更短。
在截至2006年9月30日的2年期间持续参保的160名丁丙诺啡 - 纳洛酮新用户中，84名患者（52.5%）在2004年10月1日至2005年3月31日的6个月预期间至少有1次阿片类药物的药房索赔记录，并被纳入本DUE研究。在2005年10月1日至2006年9月的12个月后期间，丁丙诺啡 - 纳洛酮的中位治疗时长为1个月，平均治疗时长为3.5个月。在12个月后期间的第1个月，只有40名患者（47.6%）有丁丙诺啡 - 纳洛酮的药房索赔记录。后期间6个月（2006年3月）时的持续用药率为27.4%（n = 23），12个月（2006年9月）时为20.2%（n = 17）。在12个月后期间，共有24名研究患者（28.6%）除丁丙诺啡 - 纳洛酮外没有其他阿片类药物的药房索赔记录。阿片类药物的使用量下降了18.8%，从预期间的每位患者每月1.49次阿片类药物药房索赔（PPPM）降至后期间的1.21次PPPM（P = 0.031）。在12个月后期间，排除0.42次丁丙诺啡 - 纳洛酮PPPM索赔后，阿片类药物的使用量下降了47.0%，从1.49次PPPM降至0.79次PPPM（P < 0.001）。在扣除成员成本分担之前，后期间包括丁丙诺啡 - 纳洛酮在内的阿片类药物实际药品成本似乎比预期间低26.9%（156.24美元/PPPM），而预期间为213.74美元/PPPM，但差异无统计学意义（P = 0.254）。排除丁丙诺啡 - 纳洛酮的成本后，阿片类药物实际药品成本从预期间的213.74美元/PPPM降至后期间的71.65美元/PPPM，下降了66.5%（P = 0.047）。
约一半有丁丙诺啡 - 纳洛酮新索赔记录的患者被排除在本研究之外，因为在起始治疗前6个月内未使用处方阿片类药物。对于起始治疗前有处方阿片类药物使用记录的患者，丁丙诺啡 - 纳洛酮治疗在随访的第一年与阿片类药物使用量和成本的降低相关。6个月时的持续用药率仅为27%，12个月时为20%，且在随访期内，当纳入丁丙诺啡 - 纳洛酮治疗的实际成本时，药品成本并无节省。
