Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-label, phase 3b study

Abstract

This open-label, phase 3b study (ClinicalTrials.gov Identifier: NCT00983073) evaluated the effectiveness, and tolerability of tapentadol for severe, chronic osteoarthritis knee pain that was inadequately managed with World Health Organization (WHO) Step I or II analgesics or co-analgesics, or that was not treated with regular analgesics. Prior to starting study treatment, patients discontinued any WHO Step II analgesics, while Step I analgesics and/or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50–250 mg bid) during a 5-week titration period and a 7-week maintenance period. Doses of tapentadol immediate release 50 mg (≤twice/day; ≥4 hours apart) were permitted throughout the study (total daily dose of tapentadol prolonged and immediate release, ≤250 mg bid). The primary endpoint was the change in pain intensity on an 11-point numerical rating scale-3 (NRS-3; recalled average pain intensity [11-point NRS] during the last 3 days) from baseline to Week 6, using the last observation carried forward (LOCF) to impute missing pain intensity scores. The mean (standard deviation) change from baseline to Week 6 (LOCF) in pain intensity was −3.4 (2.10; P < 0.0001) for all patients evaluated for effectiveness (n = 195). Significant decreases in pain intensity were also observed at Weeks 6, 8, and 12 (all P < 0.0001) using observed-case analysis. Corresponding significant improvements from baseline to Weeks 6 and 12 were observed in the Western Ontario and McMaster Universities osteoarthritis index, the EuroQol-5 Dimension health status questionnaire, the Short Form-36 health survey, and the Hospital Anxiety and Depression Scale (all P ≤ 0.0103). Treatment-emergent adverse events were in line with those observed in previous studies of tapentadol prolonged release. Overall, the results of this study indicate that tapentadol treatment results in significant improvements in pain intensity, health-related quality of life, and function in patients with inadequately managed, severe, chronic osteoarthritis knee pain.

Assessment and manifestation of central sensitisation across different chronic pain conditions

“…The effect of repeated dosing with tapentadol matches very well many chronic pain conditions (Riemsma et al, 2011) with impaired CPM such as OA pain (Steigerwald et al, 2012b), LBP (Buynak et al, 2010;Steigerwald et al, 2012a;Baron et al, 2016), painful peripheral diabetic neuropathy (Schwartz et al, 2015;Vadivelu et al, 2015), and cancer pain (Kress et al, 2014).…”

Practical Considerations for the Use of Tapentadol Prolonged Release for the Management of Severe Chronic Pain

“…33 A more rapid titration schedule may be considered for patients with uncontrolled pain. 37,38,45,56 The recommended dose range of tapentadol PR is 50 to 250 mg BID; daily doses of 4500 mg of tapentadol PR are not recommended. 33 Tapentadol PR is available in 50-, 100-, 150-, 200-, and 250-mg dose strengths.…”

“…37 The mean (SD) doses of tapentadol PR taken after the initial titration periods in each study are shown in Table I; mean total daily doses (TDDs) in the Phase IIIb studies 37,38 were lower than those observed in the Phase III studies. 23,24,30,40 This difference was possibly due to the permitted use of concomitant WHO step I analgesics or coanalgesics during study treatment (which is more representative of clinical practice) in the Phase IIIb studies, 37,38 whereas no concomitant analgesics were permitted in the Phase III studies other than paracetamol/acetaminophen, which was used as a rescue drug. 23,24,30,40 At these doses, tapentadol PR was associated with effective and tolerable relief of chronic pain.…”

“…23,24,30,40 At these doses, tapentadol PR was associated with effective and tolerable relief of chronic pain. 23,24,30,37,38,40 Efficacy data were pooled from 3 similarly designed, randomized, double-blind, Phase III studies comparing tapentadol PR (100-250 mg bid) with placebo and oxycodone hydrochloride CR (20-50 mg bid) in patients with moderate to severe, chronic low back pain (1 study 24 ) and chronic osteoarthritis pain (2 studies 23 ). Mean changes from baseline in pain intensity (last observation carried forward [LOCF]) over time from that pooled analysis are shown in Figure 2.…”

“…Tapentadol PR has been evaluated in patients with severe or moderate to severe chronic low back pain, 24,29,36,37 osteoarthritis knee pain, 23,29,38 pain associated with DPN, [39][40][41] and cancer-related pain, [42][43][44] and has been found to provide strong and reliable analgesia across a broad range of indications. Tapentadol PR has also been associated with improvements in neuropathic pain symptoms and quality of life in patients with neuropathic pain, 37,45 which are not consistently observed with classic opioid treatments.…”