Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: results of an open-label, phase 3b study

Objective: This open-label, phase 3b study evaluated the effectiveness and tolerability of tapentadol prolonged release and tapentadol immediate release (for acute pain episodes) for severe, chronic low back pain with or without a neuropathic pain component that was inadequately managed in patients taking World Health Organization (WHO) Step I or II analgesics or who were not regularly treated with analgesics. Research design and methods: Average baseline pain intensity was greater than 5 (11-point numerical rating scale-3 [NRS-3; 3-day average pain intensity]) with WHO Step I or II analgesics and greater than 6 with no regular analgesic regimen. WHO Step II analgesics were discontinued before starting study treatment; WHO Step I analgesics or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50-250 mg bid) during a 5-week titration and 7-week maintenance period. Tapentadol immediate release was permitted for acute pain episodes (tapentadol prolonged release and immediate release maximum combined dose, <= 500 mg/day). The painDETECT questionnaire was used to define subsets of patients based on the probability of a neuropathic pain component to their low back pain as 'negative', 'unclear', or 'positive'. Clinical trial registration: NCT00983385. Main outcome measure: The primary endpoint was the change from baseline to week 6 in average pain intensity (NRS-3), using the last observation carried forward to impute missing scores. Results: In the painDETECT negative (n = 49) and unclear/positive (n = 126) subsets, respectively, mean (SD) changes in pain intensity from baseline to week 6 were -2.4 (2.18) and -3.0 (2.07; both p<0.0001). Among patients who had not received prior WHO Step II treatment, lower doses of tapentadol prolonged release were generally required with increasing likelihood of a neuropathic pain component. Based on the painDETECT questionnaire and the Neuropathic Pain Symptom Inventory (NPSI), tapentadol prolonged release treatment was also associated with significant improvements in neuropathic pain symptoms, with decreases in the number of pain attacks and the duration of spontaneous pain in the last 24 hours in patients with low back pain with a neuropathic pain component (painDETECT unclear or positive score at baseline or screening). The most common treatment-emergent adverse events (incidence >= 10%, n = 176) were nausea, dizziness, headache, dry mouth, fatigue, constipation, diarrhea, nasopharyngitis, and somnolence. Conclusions: Tapentadol prolonged release was well tolerated and effective for managing severe, chronic low back pain with or without a neuropathic pain component.