Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double‐blind, Phase 3b Study

Abstract

& AbstractObjective: To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe, chronic low back pain with a neuropathic component. Methods: Eligible patients had painDETECT "unclear" or "positive" ratings and average pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day) during an 8-week comparative period. Results: In the per-protocol population (n = 288), the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation (LOCF; LSMD [95% CI], À0.066 [À0.57, 0.43]; P < 0.0001 for noninferiority). Neuropathic pain and quality-of-life measures improved significantly in both groups. Tolerability was good in both groups, in line with prior trials in the high

Validation of Pain Severity Assessment using the PainDETECT Questionnaire

“…However, a small fraction of patients who had a low PD-Q score (<13) did not demonstrate such validity. Previous longitudinal studies on drug treatment used the PD-Q score as one of the inclusion criteria (i.e., score ≥ 13) to identify patients with NeP components [8][9][10][11], and these studies successfully revealed that the experimental drug showed significant improvements in the NRS as well as the PD-Q scores. Different from these studies, a small prospective open-label study [13] used the PD-Q in addition to the NRS to evaluate cancer pain severity.…”

“…These correlations were also observed in the subset of 35 patients with a high PD-Q score (≥ 13) (current pain, r=0.38, p=0.03; average pain in the past 4 weeks, r=0.53, p=0.001; worst pain in the past 4 weeks, r=0.28, p=0.098). However, the and secondary endpoints [8][9][10][11][12][13]15]. The patients were asked to complete them twice.…”

“…Many drug studies have reported the change of the PD-Q symptom intensity and its scores over time. Some studies have reported the PD-Q score and used it to identify patients with NeP components at baseline [8][9][10][11]. Other studies have used the PD-Q to assess the response of NeP components to therapy [12,13].…”

Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models – the TapCapMentho pilot trial

“…Tapentadol (immediate release) in comparison to placebo was able to reduce laserevoked potential responses and spontaneous pain in healthy volunteers using the UVB and topical capsaicin model within a randomized trial [28] . Importantly, tapentadol also reduced symptoms and signs of neuropathic pain assessed by the PainDetect Questionnaire and NPSI questionnaire [10] . This effect is thought to result from the simultaneous modulation of the opioidergic and noradrenergic pathways.…”

“…Research indicates that noradrenergic inhibition may lead to increased and more selective efficacy in neuropathic pain. Clinical efficacy has been shown in several randomized controlled trials of acute pain [5][6][7][8] , including postoperative pain, acute low back pain, and chronic pain, e.g., in painful polyneuropathy, chronic low back pain with and without neuropathic components, and chronic osteoarthritis and cancer pain [9][10][11][12][13] .…”