Poelaert Jan, Koopmans-Klein Gineke, Dioh Alioune, Louis Frédéric, Gorissen Mayken, Logé David, Van Op den Bosch Joeri, van Megen Yvonne J B
University Hospital Brussel (VUB), Brussels, Belgium.
Mundipharma Pharmaceuticals BV, the Netherlands.
Clin Ther. 2015 Apr 1;37(4):784-92. doi: 10.1016/j.clinthera.2015.02.010. Epub 2015 Mar 7.
Laxative-refractory opioid-induced constipation (OIC) is defined as OIC despite using 2 laxatives with a different mechanism of action (based on the Anatomical Therapeutic Chemical Classification System level 4 term [contact laxatives, osmotically acting laxatives, softeners/emollients, enemas, and others]). OIC has a significant impact on the treatment and quality of life of patients with severe chronic pain. This noninterventional, observational, real-life study in Belgium investigated the efficacy of prolonged-release oxycodone/naloxone combination (PR OXN) treatment regarding pain relief and OIC compared with previous prolonged-release oxycodone (PR OXY) treatment for laxative-refractory OIC in daily clinical practice.
Laxative-refractory OIC patients with severe chronic pain were treated with PR OXN for 12 weeks (3 visits). Pain relief (assessed on a numerical rating scale) and OIC (assessed by using the Bowel Function Index [BFI]) were evaluated at each visit. A responder was defined as a patient who had: (1) no worsening of pain at the last visit compared with visit 1 or a numerical rating scale ≤4 at visit 3/last visit; and (2) a reduction in BFI ≥12 units at visit 3/last visit compared with visit 1; or (3) a BFI ≤28.8 at visit 3/last visit.
Sixty-eight laxative-refractory OIC patients with severe chronic pain (mean (sd) age 59.8 (13.3) years, 67.6% female and 91.2% non-malignant pain) were treated for 91 days with PR OXN (median daily dose, 20 mg). Treatment with PR OXN resulted in a significant and clinically relevant decrease of pain of 2.1 units (P < 0.001; 95% CI, 1.66-2.54) and of BFI by 48.5 units (P < 0.001; 95% CI, 44.4-52.7) compared with PR OXY treatment; use of laxatives was also significantly reduced (P < 0.001). Approximately 95% of patients were responders, and quality of life (as measured by using the EQ-5D) improved significantly. Adverse events were opioid related, and PR OXN treatment was well tolerated.
Treatment with PR OXN resulted in a significant and clinically relevant reduction in OIC compared with previous PR OXY treatment for these patients with severe chronic pain and laxative-refractory OIC. Treatment with PR OXN also resulted in a significant improvement in pain relief and quality of life. ClinicalTrials.gov identifier: NCT01710917.
顽固性阿片类药物引起的便秘（OIC）是指尽管使用了两种作用机制不同的泻药（基于解剖治疗化学分类系统4级术语[接触性泻药、渗透性泻药、软化剂/润肤剂、灌肠剂及其他]）仍存在的OIC。OIC对严重慢性疼痛患者的治疗和生活质量有重大影响。这项在比利时开展的非干预性、观察性、真实生活研究，探讨了与先前用于治疗顽固性OIC的缓释羟考酮（PR OXY）相比，缓释羟考酮/纳洛酮组合（PR OXN）治疗在缓解疼痛和OIC方面的疗效。
患有严重慢性疼痛的顽固性OIC患者接受PR OXN治疗12周（3次就诊）。每次就诊时评估疼痛缓解情况（采用数字评分量表）和OIC（采用肠道功能指数[BFI]评估）。有以下情况的患者被定义为有反应者：（1）与第1次就诊相比，最后一次就诊时疼痛没有加重，或在第3次就诊/最后一次就诊时数字评分量表≤4；（2）与第1次就诊相比，在第3次就诊/最后一次就诊时BFI降低≥12个单位；或（3）在第3次就诊/最后一次就诊时BFI≤28.8。
68例患有严重慢性疼痛的顽固性OIC患者（平均（标准差）年龄59.8（13.3）岁，67.6%为女性，91.2%为非恶性疼痛）接受PR OXN治疗91天（中位日剂量20 mg）。与PR OXY治疗相比，PR OXN治疗使疼痛显著且具有临床意义地降低了2.1个单位（P<0.001；95%置信区间，1.66 - 2.54），BFI降低了48.5个单位（P<0.001；95%置信区间，44.4 - 52.7）；泻药的使用也显著减少（P<0.001）。约95%的患者有反应，生活质量（采用EQ - 5D测量）显著改善。不良事件与阿片类药物相关，PR OXN治疗耐受性良好。
与先前用于这些患有严重慢性疼痛和顽固性OIC患者的PR OXY治疗相比，PR OXN治疗使OIC显著且具有临床意义地减轻。PR OXN治疗还使疼痛缓解和生活质量显著改善。ClinicalTrials.gov标识符：NCT01710917。
