A Multicentre, Randomised, Double-Blind Study Comparing the Efficacy

Abstract and Introduction

Abstract

Background: Low back pain is an important medical problem in Western industrialized countries. NSAIDs are one of the main options for symptomatic pain relief in the early management of this painful condition. Dexketoprofen is an NSAID belonging to the arylpropionic acid group that has demonstrated good analgesic efficacy and a good safety profile in different acute and chronic painful conditions.
Methods: A randomized, double-blind, parallel, active controlled, multicentre study that included 370 outpatients with acute low back pain was conducted to compare the analgesic efficacy of dexketoprofen 50mg twice daily versus diclofenac 75mg twice daily administered intramuscularly for 2 days. Efficacy outcomes were assessment of pain intensity (PI) measured on a visual analogue scale, total PI scores from baseline to 6 hours after the first-dose administration (primary efficacy endpoint; SAPID_0-6), score on a physical disability scale using the Roland Disability Questionnaire (RDQ), and use of rescue medication. Tolerability and safety were also assessed as secondary variables.
Results: The adjusted mean (SAPID_0-6) scores were very similar, 117.3 mm/h with dexketoprofen and 114.7 mm/h with diclofenac. The adjusted ratio of means was 1.023 and the lower 95% confidence limit was 0.81, demonstrating non-inferiority of dexketoprofen (defined by a lower limit of the 95% CI >0.80) in comparison with diclofenac (per-protocol analysis). The median change in the RDQ was -6 points for both groups (p = 0.69), showing an overall improvement on the disability scale. No significant differences between groups were observed regarding the percentage of patients needing rescue medication or in the mean values of pain after repeated doses (SAPID_0-last). Dexketoprofen was well tolerated, with a reported incidence of adverse events similar to that of diclofenac. No serious adverse events were reported in either treatment group.
Conclusion: From the results of this study it can be concluded that dexketoprofen 50mg administered twice daily intramuscularly provides a clinically relevant analgesic effect with good tolerability after single and repeated doses in patients with acute severe low back pain.

Introduction

Musculoskeletal symptoms of various types (neck pain, limb pain, low back pain, joint pain and chronic widespread pain) are a major reason for consultation in primary care.^[1] Among these, low back pain is particularly common and considered an important medical problem in Western industrialized countries.^[2] About two-thirds of adults experience low back pain at some time, with a peak prevalence in those aged between 35 and 55 years.^[3,4,5] The disability associated with back problems has increased 4-fold since the late 1970s.^[3]

Low back pain can be caused by many conditions, both serious and benign. Mechanical causes account for approximately 97% of cases, mainly lumbar strains and sprains and age-related degenerative processes of discs and facets, and less frequently herniated disk and osteoporotic compression fracture.^[4] Non-mechanical spinal conditions such as neoplasia, infection and inflammatory arthritis as well as visceral diseases are less common causes of low back pain. According to the different clinical guidelines, patients with low back pain can be classified as having: (1) nonspecific low back pain (about 85% of patients), which is not attributable to a recognisable pathology, (2) specific low back pain or serious spinal pathology ('red flag' conditions such as tumour, infection or fracture), or (3) radicular pain. Diagnostic procedures should focus on identification of 'red flags' and exclusion of specific diseases.^[6]

Acute episodes of low back pain lasting <3 months (90% of cases) are usually benign and self-limiting (90% of people recover within 6 weeks), although 2-7% of subjects develop chronic pain.^[7,8,9] Furthermore, acute low back pain has a high recurrence rate with symptoms recurring, to a lesser degree, in 50-80% of people within a year. However, a population-based cohort study indicated that most new episodes and >80% of cases of recurrent low back pain are mild and not disabling.^[10]

Many reviews and assessment or treatment guidelines are available to help the primary-care doctor manage acute low back pain.^[6,11] The aims of treatment of acute low back pain are to relieve pain, improve functional ability and prevent recurrence and chronicity. Current recommendations include: adequate information and reassurance; advice to stay active and continue normal activities; analgesia, if necessary; and consideration of spinal manipulation for patients who are failing to return to normal activities. Bed rest, back-specific exercises, epidural corticosteroids and traction are strongly discouraged.^[11] Randomized, controlled trials in the primary-care setting have demonstrated that selected information and advice for patients with acute low back pain can have a positive effect on a patient's beliefs and clinical outcomes.^[12,13] Recommendations for the prescription of medications are generally consistent across different guidelines. Prescription of NSAIDs is one of the main pharmacological options for symptomatic relief in the early management of low back pain.^[6,11] Parenteral administration may be preferable, especially in severe cases, because of the more rapid onset of action.^[14]

Dexketoprofen is an NSAID with analgesic, anti-inflammatory and antipyretic actions belonging to the 2-arylpropionic acid family.^[15] Dexketoprofen is the S(+) enantiomer of the racemic compound ketoprofen and acts on both isoenzymes of cyclo-oxygenase (COX).^{[16,17,18,19]} As with other arylpropionic acid derivatives, it has been shown that the levorotatory enantiomer (- or R) does not contribute to the efficacy of the racemic drug, but may have an influence on the safety profile of dexketoprofen.^[15] Dexketoprofen has been developed as the tromethamine salt (dexketoprofen trometamol), a formulation with high water solubility.

Dexketoprofen is available orally as standard immediate-release tablets of 12.5 and 25mg in several European countries and in many countries not in the EU. The pharmacokinetics of oral and parenteral dexketoprofen have been widely studied.^[20,21,22] The analgesic efficacy of dexketoprofen administered orally has also been demonstrated in several studies.^{[23,24,25,26,27,28,29]} These studies were conducted in different mild to moderate acute and chronic painful conditions, such as dental pain, musculoskeletal pain, dysmenorrhoea and cancer pain. The results of these studies showed that dexketoprofen has good analgesic and safety profiles, comparable to those of other NSAIDs. Moreover, there is a strong suggestion of a faster onset of analgesic effect with dexketoprofen in comparison with some of its comparators, such as ibuprofen and ketoprofen.^[23,24,26]

Based on the efficacy and safety evidence for the oral formulation, a solution for parenteral (intra-venous and intramuscular) administration of dexketoprofen has been developed and recently marketed for managing different painful conditions of moderate to severe intensity, such as postoperative pain, musculoskeletal pain and renal colic. Administration of dexketoprofen by the parenteral route has demonstrated good analgesic and safety profiles in both renal colic^[30,31] and postoperative pain.^[32,33,34] The aim of this study was to evaluate the efficacy and tolerability of dexketoprofen administered intramuscularly in patients with acute low back pain, after single and repeated doses, in comparison with diclofenac, a reference therapy commonly used in this indication.^[14,35,36]

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