Krebs Erin E, Gravely Amy, Nugent Sean, Jensen Agnes C, DeRonne Beth, Goldsmith Elizabeth S, Kroenke Kurt, Bair Matthew J, Noorbaloochi Siamak
Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.
Department of Medicine, University of Minnesota Medical School, Minneapolis.
JAMA. 2018 Mar 6;319(9):872-882. doi: 10.1001/jama.2018.0899.
Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.
To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects.
DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized.
Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response.
The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19).
Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, -0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]).
Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.
clinicaltrials.gov Identifier: NCT01583985.
与非阿片类药物相比，关于阿片类药物用于慢性疼痛的长期疗效的证据有限。
比较阿片类药物与非阿片类药物在12个月内对疼痛相关功能、疼痛强度及不良反应的影响。
设计、地点和参与者：这是一项为期12个月的实用随机试验，采用盲法评估结果。患者于2013年6月至2015年12月从退伍军人事务部初级保健诊所招募；随访于2016年12月完成。符合条件的患者尽管使用了镇痛药，但仍患有中度至重度慢性背痛或髋部或膝部骨关节炎疼痛。在265名登记患者中，25名在随机分组前退出，240名被随机分组。
两种干预措施（阿片类药物和非阿片类药物治疗）均遵循以改善疼痛和功能为目标的靶向治疗策略。每种干预措施都有自己的处方策略，包括3个步骤中的多种药物选择。在阿片类药物组中，第一步是速释吗啡、羟考酮或氢可酮/对乙酰氨基酚。对于非阿片类药物组，第一步是对乙酰氨基酚（扑热息痛）或非甾体抗炎药。根据个体患者的反应，在指定治疗组内更换、添加或调整药物。
主要结局是12个月内的疼痛相关功能（简明疼痛量表[BPI]干扰量表），主要次要结局是疼痛强度（BPI严重程度量表）。对于两个BPI量表（范围为0 - 10；分数越高 = 功能越差或疼痛强度越高），1分的改善具有临床意义。主要不良结局是药物相关症状（患者报告的清单；范围为0 - 19）。
在240名随机分组的患者中（平均年龄58.3岁；女性32名[13.0%]），234名（97.5%）完成了试验。两组在12个月内的疼痛相关功能方面无显著差异（总体P = 0.58）；阿片类药物组12个月的平均BPI干扰为3.4，非阿片类药物组为3.
