Abstract
This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated. Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1). Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P < 0.0001 vs. the null responder hypothesis rate [<60%]), resulting in a positive trial despite premature termination (136 recruited of 180 planned). Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P < 0.05). Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone, buprenorphine, fentanyl, morphine, and hydromorphone. The prevalences of adverse events reported as the reason for switching to tapentadol (most commonly constipation and nausea) decreased over time. Tapentadol PR (50-250 mg b.i.d.) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.
Highlights
This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50−250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to WorldClinicalTrials.gov #NCT00986258.Enhanced content for Advances in Therapy articles is available on the journal web site: www.advancesintherapy.comHealth Organization (WHO) step III opioids but tolerating treatment poorly
A total of 125 patients were included in the safety population, 123 patients were included in the main analysis population, and 94 patients were included in the per-protocol population
As described previously, screening and baseline painDETECT and Neuropathic Pain Symptom Inventory (NPSI) results may have been affected by prior treatment. It is recognized more and more by the scientific community that real-world effectiveness trials are of great value, as they are highly related to routine clinical practice and avoid the artificial settings and patient selection requirements that are commonly required for trials driven by regulatory guidelines. Results of this open-label, phase 3b study support those of previous, randomized, doubleblind, controlled, phase 3 studies of tapentadol PR for moderate-to-severe, chronic low back pain [18] and neuropathic pain [20]
Summary
This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50−250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to WorldClinicalTrials.gov #NCT00986258.Enhanced content for Advances in Therapy articles is available on the journal web site: www.advancesintherapy.comHealth Organization (WHO) step III opioids but tolerating treatment poorly. Chronic therapy with opioid analgesics may result in development of tolerance, such that patients require higher average doses to maintain effective analgesia but potentially leading to more side effects [12]. Such tolerance development is another major reason why patients require opioid rotation [12]. The vast majority of physicians (>90%) report using combination treatment rather than monotherapy for the management of severe, chronic pain [13]; a recent Cochrane review by Chaparro and colleagues [14] of randomized controlled trials evaluating combination therapy for neuropathic pain found that combination therapy offered similar or sometimes a modest gain in efficacy, it was often associated with higher incidences of side effects and discontinuations due to side effects
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