Efficacy and tolerability of flupirtine in subacute/ chronic musculoskeletal pain - results of a patient level, pooled re-analysis of randomized, double-blind, controlled trials.

INTRODUCTION: Flupirtine, a nonopioid analgesic without antipyretic or antiphlogistic properties, constitutes a unique class within the group of WHO-I analgesics. First approved in Germany on a national level in 1989, this selective neuronal potassium channel opener evolved rapidly into one of the most preferred analgesics for the treatment of musculoskeletal pain in some European countries. However, its use outside Europe was limited due to a discrepancy between the empirical application of the drug and supporting evidence. As a consequence, the German Pain Society commissioned an independent research institute to perform a pooled re-analysis of all available data from randomized controlled trials (including some trial not yet published). METHODS: A retrospective pooled analysis of the individual patient data from 8 randomized controlled Phase III - IV clinical trials was carried out which included patients with sub-acute and chronic musculoskeletal pain. The efficacy and tolerability of flupirtine at dosages of 100 - 400 mg/d were compared to placebo and/or active comparators. Data were pooled by treatment and by subject. The primary endpoint was the average change in pain intensity for the overall maintenance period. RESULTS: A total of 1,046 patients was evaluated for efficacy and 1,095 patients for safety. Based on 3,337 pain assessments, treatment with flupirtine and active comparators resulted in significant reductions in pain intensity compared to baseline beginning from Day 4 (flupirtine) and Day 5 (comparators) and continuing up to the end of the study period as well as during the overall maintenance period (all p < 0.001). Flupirtine prooved to be non-inferior to the active comparators (p < 0.001) but showed a superior tolerability profile with a significantly lower number of patients reporting treatment emergent adverse events (28.6 vs. 39.1%, p < 0.001) and a significantly lower percentage of patients who prematurely discontinued study medication due to these adverse events (7.1 vs. 11.7%, p = 0.013). LIMITATIONS: The limitations in the study were confined to those inherent in the retrospective and pooled analysis design. CONCLUSION: On the basis of this pooled analysis of individual data from 8 controlled clinical trials involving patients suffering from sub-acute/chronic musculoskeletal pain, the efficacy of flupirtine was superior to placebo across its effective and approved dosage range. Flupirtine was at least as active as the active comparators and showed a superior tolerability profile with a significantly lower treatment discontinuation rate.

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

[Flupirtine in acute and chronic pain associated with muscle tenseness. Results of a postmarket surveillance study]. / Flupirtin bei muskuloskelettalen Schmerzen. Ergebnisse einer Anwendungsbeobachtung.

BACKGROUND: Flupirtine with its specific mode of action as Selective Neuronal Potassium Channel Opener (SNEPCO) shows analgesic, muscle tone normalizing properties and iprotects from chronification. By means of an open multicentre drug monitoring study new data should be accumulated in terms of efficacy and patient's tolerance of flupirtine upon treatment of acute and chronic pain associated with muscle tenseness. RESULTS: Regarding acute and chronic pain, significant reduction of pain intensity, pain upon pressure and muscular tenseness could be proved. Simultaneously, decrease of sleep disorders due to pain and strong reduction of restrictions in daily life caused by pain improved distinctly patient's quality of life. Efficacy and tolerance has mainly been rated as good and very good respectively by physicians and patients, the number of undesired drug reactions being under 1%. CONCLUSION: Data of this study confirm the analgesic and muscle tone normalizing efficacy of flupirtine upon treatment of acute and chronic pain associated with muscle tenseness and show, that flupirtine has to be considered as a substance of first choice for the treatment of these disorders.

Cost effectiveness of intrathecal therapy for pain.

Successful management of chronic cancer and nonmalignant pain remains a challenge to clinicians, and cost effectiveness is an important consideration for clinical decision making. Although the oral route was previously considered the optimal method of chronic opioid administration, emerging evidence demonstrates a therapeutic advantage to intrathecal opioid delivery compared to alternative modalities. Intrathecal drug delivery uses an implantable drug infusion system to deliver very low doses of opioids and other analgesics directly into the intrathecal space. Although the initial costs of surgical implantation of an intrathecal pump appear to be substantial, maintenance costs of intrathecal drug delivery over time are significantly lower than other routes of administration, including oral and intravenous drug delivery. Cost analyses of alternate routes of opioid administration indicate that intrathecal delivery is the most cost-effective route of opioid administration for patients who require long-term management of cancer (≥ 3-6 months) or nonmalignant pain (≥ 11-22 months).