tapentadol and Musculoskeletal-Pain

Musculoskeletal pain, encompassing back and osteoarthritis (OA) pain, represents the most frequent source of chronic pain in western countries, and it is particularly frequent in older adults. Remarkably, back and OA pain present, in most cases, both a nociceptive and a neuropathic component of pain. Treatment selection should, therefore, properly consider the ability of a drug to act on both components, reducing the possibility of plastic changes in the central nervous system, and consequently promoting physical rehabilitation. The pharmacological profile of tapentadol, combining synergistically µ-opioid receptor (MOR) agonist and norepinephrine reuptake inhibition (NRI) in one single molecule with a concomitant reduction in the burden of adverse events, is unique, to date, and makes this drug particularly suitable for the treatment of back pain and OA-associated pain, especially when a neuropathic component is present. Tapentadol is an innovative dual-acting analgesic molecule, which combines two mechanisms of action, namely MOR agonism and NRI. This narrative review will briefly discuss the pharmacological action of tapentadol and its rationale for use in back pain and OA.

Topics: Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Tapentadol; Therapies, Investigational; Treatment Outcome

Chronic musculoskeletal pain is a prevalent condition and a major cause of disability and absence from the workplace worldwide. Opioids are frequently used to treat chronic pain, although adverse effects often restrict their long-term benefits. Tapentadol is an opioid and norepinephrine re-uptake inhibitor, which may cause a lower incidence (and severity) of adverse effects compared to other strong opioids.. To determine the efficacy, safety and tolerability of tapentadol extended release for moderate-to-severe pain for at least three months for any musculoskeletal cause.. We searched electronic databases (CENTRAL, MEDLINE, EMBASE, Web of Science) to March 2014, unrestricted by language, as well as trials registers and reference lists from retrieved studies. We contacted drug manufacturers for further information.. Randomised controlled trials (RCTs) of tapentadol in people with chronic musculoskeletal pain, compared to placebo or active control.. Two review authors independently selected trials for inclusion, assessed risk of bias of included studies and extracted data. We performed two meta-analyses for the comparisons tapentadol extended release vs. placebo, and tapentadol extended release vs. active-control (oxycodone). We used random-effects and fixed-effect models according to the presence or not of heterogeneity, respectively. Also, we performed subgroup analyses. The primary efficacy outcome was pain control assessed by change in pain intensity scores and responder's rate (at least 50% pain relief). Primary safety outcome was withdrawal rate due to adverse effects.. Four parallel-design RCTs of moderate quality including 4094 patients with osteoarthritis or back pain, or both, met the inclusion criteria. Three trials were phase III studies with 12-weeks follow-up and the fourth trial was an open-label safety study of 52-weeks follow-up. All trials were oxycodone-controlled and three were also placebo-controlled. Two trials included patients with knee osteoarthritis, one evaluated patients with low back pain and one enrolled both. All studies reported last-observation-carried-forward (LOCF) as imputation method. We requested baseline-observation-carried-forward (BOCF) imputed analyses and any unpublished data from the manufacturer but the manufacturers denied the request. Two out of the four oxycodone-controlled studies and one out of the three placebo-controlled studies did not provided data on responder's rate. Two studies were considered to be of high risk of bias.In comparison to placebo, tapentadol was associated with a mean reduction of 0.56 points (95% confidence interval (CI) 0.92 to 0.20) in the 11-point numerical rating scale (NRS) at 12 weeks and with a 1.36 increase (95% CI 1.13 to 1.64) in the risk of responding to treatment (number needed to treat for an additional beneficial outcome (NNTB) 16; 95% CI 9 to 57, for 12-weeks). Moderate-to-high heterogeneity was found for the efficacy outcome estimates. Tapentadol was associated with a 2.7 fold increase (95% CI 2.05 to 3.52) in the risk of discontinuing treatment due to adverse effects number needed to treat for an additional harmful outcome (NNTH) 10; 95%CI 7 to 12, for 12 weeks).In comparison to oxycodone, pooled data showed a 0.24 points (95%CI 0.43 to 0.05) reduction in pain intensity from baseline in the 11-point NRS. The two studies that evaluated responder's rate showed a non-significant 1.46 increase (95% CI 0.92 to 2.32) in the risk of responding to treatment among tapentadol treated patients. Tapentadol was associated with a 50% risk reduction (95% CI 42% to 60%) of discontinuing treatment due to adverse effects (NNTB 6; 95% CI 5 to 7, for 12 weeks). Tapentadol was also associated with a 9% reduction (95% CI 4 to 15) in the overall risk of adverse effects (NNTH 18; 95% CI 12 to 35, for 12 weeks) and with a non-significant 43% reduction (95% CI 33 to 76) in the risk of serious adverse effects. Moderate to high heterogeneity was found for most efficacy (except for the primary outcome) and safety outcome estimates. Subgroup analysis showed a higher i. Tapentadol extended release is associated with a reduction in pain intensity in comparison to placebo and oxycodone. However, the clinical significance of the results is uncertain due to the following reasons: modest difference between interventions in efficacy outcomes, high heterogeneity in some comparisons and outcomes, high withdrawals rates, lack of data for the primary outcome in some studies and impossibility to use BOCF as imputation method. Tapentadol is associated with a more favourable safety profile and tolerability than oxycodone.

Topics: Adult; Analgesics, Opioid; Chronic Pain; Clinical Trials, Phase III as Topic; Humans; Low Back Pain; Musculoskeletal Pain; Osteoarthritis, Knee; Oxycodone; Phenols; Randomized Controlled Trials as Topic; Tapentadol

Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Efficacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients' long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profile, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic field, particularly in the treatment of osteoarthritis and low back pain.

Topics: Adult; Chronic Pain; Clinical Trials as Topic; Cost of Illness; Europe; Humans; Multicenter Studies as Topic; Musculoskeletal Pain; Narcotics; Neuralgia; Nociception; Norepinephrine Plasma Membrane Transport Proteins; Osteoarthritis; Phenols; Receptors, Opioid, mu; Tapentadol; Therapies, Investigational; United States

Chronic pain is a leading cause of disability and represents a relevant societal burden. Opioids are widely used for managing chronic non-cancer pain; however, the high incidence of side effects is often the main reason for discontinuation. Two formulations have recently been studied to improve the tolerability of opioids (tapentadol extended release [ER] and oxycodone/naloxone ER), but a direct comparison between these drugs is not available in the literature. The comparative cost effectiveness of these two drugs has not previously been assessed. The objective of this meta-analysis is a clinical and economic evaluation of tapentadol ER and oxycodone/naloxone ER for the treatment of musculoskeletal pain, by indirect comparison with controlled release (CR) oxycodone.. A structured literature review was conducted to identify published data for the health-economic model. The authors performed a meta-analysis on three selected randomized controlled trials (RCTs) for each treatment (tapentadol ER and oxycodone/naloxone ER). As measure of treatment effect, risk ratio was calculated, compared to the control active treatment (CR oxycodone), for the following outcomes: discontinuation rate due to adverse events, due to gastrointestinal (GE) side effects and central nervous system (CNS) side effects. A Markov model was developed to compare the cost effectiveness of tapentadol ER and oxycodone/naloxone ER. Four health states were defined: (1) patients still on treatment; (2) occurrence of adverse events (gastroenterology, central nervous system); (3) treatment discontinuation as consequence of ineffectiveness of treatment; and (4) treatment discontinuation as consequence of adverse events.. Both drugs showed a significant clinical advantage over the active control, CR oxycodone; however, tapentadol ER resulted in a better risk ratio reduction for the primary outcome of discontinuation rate due to adverse events and for the secondary outcome nausea and vomiting. The two drugs gave equivalent results in the capacity of reduction of constipation risk. In the economic evaluation both interventions were cost effective compared with CR oxycodone. However, tapentadol ER showed the most favorable results as in 65% of cases it was less costly and produced a considerable quality adjusted life years (QALY) gain. The higher impact of tapentadol ER on the cost effectiveness results was probably due to the price and the lower incidence of adverse events and related discontinuation rate, resulting in a further economic advantage.. Both tapentadol ER and oxycodone/naloxone ER are cost effective interventions compared with CR oxycodone; however, tapentadol ER was shown to provide better clinical outcomes at lower costs.

Topics: Chronic Pain; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Italy; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols; Tapentadol; Treatment Outcome

Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Double-Blind Method; Female; Functional Status; Humans; Low Back Pain; Male; Middle Aged; Musculoskeletal Pain; Osteoarthritis; Outcome Assessment, Health Care; Quality of Life; Tapentadol

Current evidence shows that tapentadol hydrochloride prolonged-release is more cost effective than other opioids. However, the introduction into the market of generic formulations of traditional comparators, leading to potential savings due to their lower price, creates space for further research. The objective of this study is to evaluate and compare the efficacy of tapentadol versus oxycodone/naloxone and the economic impact of the two alternatives in both branded and generic formulations.. A cost-effectiveness analysis was performed using the third-payer perspective (TPP), with specific reference to the Italian National Health Service. A Markov model was implemented to simulate transitions between states, comparing two arms: The first arm simulated the administration of tapentadol, while the second simulated the administration of oxycodone/naloxone, both branded and generic. The results were reported in terms of net monetary benefit (NMB). The willingness to pay (WPT) was estimated at €35,000/quality-adjusted life year.. Tapentadol was dominant in all scenarios, assuming a population of 1000 individuals over a 1-year time horizon. In all cases, although the prices of oxycodone/naloxone generic formulations were lower, the costs associated with treatment discontinuation were always higher than those associated with tapentadol. The comparison with the branded formulation of oxycodone/naloxone was associated with the highest savings of €431.77 per patient, and with the highest NMB of €1943.77 per patient.. The results of this pharmacoeconomic evaluation promote the use of tapentadol in comparison with oxycodone/naloxone, confirming the results obtained in previous studies with reference to the generic formulations.

Topics: Analgesics, Opioid; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols; State Medicine; Tapentadol

Topics: Analgesics, Opioid; Humans; Musculoskeletal Pain; Receptors, Opioid, mu; Tapentadol

The use of long-term opioids for the management of chronic musculoskeletal pain is a hot topic in the scientific community, especially when it concerns the elderly. This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining μ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain. The effect of this molecule on anxiety, depression, cognitive status, and overall quality of life were investigated.. This was a spontaneous, observational, open-label, prospective study, in 80 older patients aged ≥80 years, naïve to strong opioids, presenting moderate-to-severe chronic pain from different etiologies. Tapentadol PR was initially prescribed at the dose of 25-50 mg/day and increased gradually in case of insufficient analgesia. Pain intensity was assessed by a 10-point Numeric Rating Scale (NRS). Other endpoints were as follows: DN4 questionnaire for the evaluation of the neuropathic component of pain, SF12, HADS, and MMSE questionnaires to evaluate the quality of life, anxiety, and cognitive impairment, respectively. Safety evaluations were also performed through the assessment of the frequency and severity of adverse events.. At T45, NRS score reduction was achieved in 86.0% of patients. On average, pain decreased by 55% from a mean of 8.2 to a mean of 3.6. At T90, tapentadol PR did not affect the psychophysical and cognitive abilities of older patients.. The benefits with tapentadol PR in controlling pain have improved the quality of life of our patients, also showing a favorable effect on their cognitive performance.

Topics: Aged, 80 and over; Analgesics, Opioid; Anxiety; Chronic Pain; Cognitive Dysfunction; Delayed-Action Preparations; Depression; Female; Follow-Up Studies; Humans; Male; Musculoskeletal Pain; Pain Management; Prospective Studies; Quality of Life; Tapentadol

Chronic pain is highly prevalent in the elderly, and the prolonged use of long-term opioids for the management of chronic musculoskeletal pain is controversial. Tapentadol, combining μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI) in a unique mechanism of action, may be a valid option for chronic pain management in the geriatric population. The aim of the study was to assess the efficacy and tolerability of tapentadol prolonged release (PR), administered to patients aged ≥ 70 years with chronic pain.. A total of 20 elderlies, naïve to opioids and with persistent moderate-to-severe chronic pain from different etiologies received tapentadol PR with up-titrations as necessary. The response to treatment, defined as at least 30% reduction in pain intensity compared with baseline, was the primary endpoint. Secondary endpoints were pain intensity on the Numeric Rating Scale (NRS) both at rest and during loading and sleep quality.. Tapentadol PR was safe and effective in our population of elderlies with chronic pain from different etiologies: pain intensity compared with baseline, both at rest and during load, was statistically lower at each visit (p<0.01), whereas sleep quality improved significantly throughout the study (p<0.05). Only few minor side effects were reported, with an overall good safety profile and a very high tolerability and satisfaction for treatment.. Tapentadol PR, adequately titrated according to patients' response in naïve subjects, is safe and effective to control pain in the elderly.

Topics: Aged; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Female; Frail Elderly; Humans; Male; Musculoskeletal Pain; Pain Measurement; Prospective Studies; Severity of Illness Index; Tapentadol