Effectiveness and Tolerability of Tapentadol Prolonged Release Compared With Prior Opioid Therapy for the Management of Severe, Chronic Osteoarthritis Pain

Abstract

BackgroundTapentadol prolonged release (PR; 100–250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment.ObjectiveThe objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50–250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability.MethodsThis open-label, phase 3b study (NCT00982280) was conducted from October 2009 through June 2010 (prematurely terminated due to slow recruitment and study drug shortages) in clinical care settings in Europe and Australia. The study population included patients with severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening, responded to therapy (average pain intensity [11-point numerical rating scale-3 (NRS-3)] ≤5 at screening), and reported opioid-related adverse effects as their reason for changing analgesics. Patients switched directly from WHO step III therapy to tapentadol. Patients received oral tapentadol PR (50–250 mg twice daily) during 5-week titration and 7-week maintenance periods. Oral tapentadol immediate release (IR) was permitted (≤twice/day, ≥4 h apart) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids (combined dose of tapentadol [PR and IR] ≤500 mg/day). This study was planned to evaluate conversion to tapentadol PR, based on responder rate 1 (percentage of patients with same/less pain [NRS-3] versus Week −1) at Week 6 (primary endpoint), adverse events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids (PR and PR plus IR formulations).ResultsOf 82 patients enrolled, 63 received study medication. In the per-protocol population, responder rate 1 at Week 6 (last observation carried forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis population. In the safety population, prevalence of AEs reported as associated with prior opioids at Week −1 (reasons for rotation) and related to tapentadol treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 %), and withdrawal of consent (1.6 %).ConclusionsSign...

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

“…Because of tapentadol's favorable tolerability profile, it may be possible to titrate tapentadol PR to doses above the equianalgesic doses of previous opioids, thereby offering the potential for added analgesia. The successful rotation of patients from previous strong (WHO step III) opioids to tapentadol PR has been reported in 2 recent Phase IIIb studies 45,56 in patients with severe chronic low back pain or osteoarthritis pain who had responded to WHO step III opioids but showed poor tolerability. The starting doses in these 2 studies 45,56 were based on the morphine equivalent doses of all previous opioids used ( Table IV.…”

“…The successful rotation of patients from previous strong (WHO step III) opioids to tapentadol PR has been reported in 2 recent Phase IIIb studies 45,56 in patients with severe chronic low back pain or osteoarthritis pain who had responded to WHO step III opioids but showed poor tolerability. The starting doses in these 2 studies 45,56 were based on the morphine equivalent doses of all previous opioids used ( Table IV. 45 Although the number of patients used to determine each of these equianalgesic ratios was relatively small, the equianalgesic ratio determined for tapentadol PR to oxycodone CR in this Phase IIIb study 45 was in line with that observed in a pooled analysis of data from randomized, double-blind, placebo-and activecontrolled, Phase III studies comparing tapentadol PR and oxycodone CR, 29 and was confirmed in a second Phase IIIb study of similar design.…”

“…45 Although the number of patients used to determine each of these equianalgesic ratios was relatively small, the equianalgesic ratio determined for tapentadol PR to oxycodone CR in this Phase IIIb study 45 was in line with that observed in a pooled analysis of data from randomized, double-blind, placebo-and activecontrolled, Phase III studies comparing tapentadol PR and oxycodone CR, 29 and was confirmed in a second Phase IIIb study of similar design. 56 In both studies, 45,67 the prevalence of TEAEs that were reported as the reason for switching from previous WHO step III therapy (most commonly constipation and nausea) decreased with tapentadol treatment ( Figure 6). Approximately 6% of patients in the osteoarthritis study 45 and 20% of patients in the low back pain study 4 experienced drug withdrawal syndrome, largely on switching from their previous strong opioid to tapentadol PR.…”

“…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.…”

Current views of the development of pain syndrome mechanisms in patients with osteoarthrosis. Rational pharmacotherapy

“…На фоне лече-ния отмечалось уменьшение количества болевых присту-пов и продолжительности спонтанной боли. Кроме того, монотерапия двойного действия характеризуется лучшей переносимостью и большей эффективностью по сравне-нию с использованием других опиоидов [47].…”