Efficacy and tolerability of the antispasmodic, pridinol, in patients with muscle-pain - results of primepain, a retrospective analysis of open-label real-world data provided by the German pain E-registry.

OBJECTIVE: To evaluate efficacy and tolerability of the nonbenzodiazepine antispasmodic pridinol (PRI), as an add-on treatment in patients with muscle-related pain (MRP). METHODS: Exploratory retrospective analysis of depersonalized routine data provided by the German Pain e-Registry (GPeR) focusing on pain intensity, pain-related disabilities in daily life, wellbeing, and drug-related adverse events (DRAEs).Primary endpoint based on a global response composite of (a) a clinically relevant analgesic response (relative improvement ≥50% and/or absolute improvement ≥ the minimal clinical important difference) for pain intensity and disability in combination with (b) an improvement in wellbeing (all at end of treatment vs. baseline), and (c) lack of any DRAEs. RESULTS: Between 1 January 2018 and 31 December 2020, the GPeR collected information on 121,803 pain patients of whom 1133 (0.9%; 54.5% female, mean ± SD age: 53.9 ± 11.8 years) received add-on PRI for the treatment of (mostly acute) MRP originating predominantly in the (lower) back (43.2%), lower limb (26.4%), or should/neck (21.1%). Average daily dose was 7.8 ± 1.8 (median 9, range 1.5-13.5) mg, duration of treatment 12.0 ± 10.2 (median 7, range 3-63) days. In total, 666 patients (58.8%) reported a complete, 395 (34.9%) a partial, and 72 (6.4%) patients no response - either because of lack of efficacy (n = 2, 0.2%) or DRAEs (n = 70, 6.2%). In response to PRI, 41.7% of patients documented a reduction of at least one other pain medication and 30.8% even the complete cessation of any other pharmacological pain treatments. CONCLUSION: Based on this real-world data of the German Pain e-Registry, add-on treatment with PRI in patients with acute MRP under real-world conditions in daily life was well tolerated and associated with an improvement of pain intensity, pain-related disabilities, and overall wellbeing.

Muscle pain is one of the most common pain problems worldwide.In the majority of cases, muscle pain is temporary, transient, and benign in nature. However, people affected may still experience severe pain and significant pain-related disabilities in daily life activities that may require temporary drug treatment ­ also to be able to undertake the non-drug treatment measures necessary to prevent recurrence.Current treatment recommendations for muscle pain are largely "non-specific" and limited to symptomatic pain-relieving measures (e.g. NSAIDs), whereas muscle relaxants are currently not recommended (primarily due to insufficient efficacy data from controlled clinical trials) but are nevertheless frequently prescribed.In our analysis of depersonalized data from the German Pain e-Registry, the add-on treatment with pridinol proved to be effective and well tolerated in patients with muscle pain who have so far responded only insufficiently to recommended analgesic and adjuvant therapiesThe available real-world evidence data on efficacy and tolerability of PRI show a beneficial and clinically relevant activity, but confirmation by active or placebo-controlled clinical studies is still lacking.

Efficacy and safety/tolerability of pridinol: a meta-analysis of double-blind, randomized, placebo-controlled trials in adult patients with muscle pain.

OBJECTIVE: To evaluate analgesic efficacy and safety/tolerability of the nonbenzodiazepine antispasmodic pridinol (PRI) in patients with muscle-related pain. METHODS: Systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) according to PRISMA guidelines and Cochrane recommendations. Data sources included Google Scholar, Embase, PubMed, ClinicalTrials.gov, EU Clinical Trials Registry, Chinese Clinical Trial Registry, UMIN Clinical Trials Registry, and product manufacturer archives from inception to 31 January 2022. Eligibility criteria for study selection were randomized, placebo-controlled trials with PRI in adults (≥18 years) with muscle-related pain. Data extraction, synthesis, and analysis carried out by two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Categorial global response rates (number of patients) based on clinical judgement of study physicians (as primary efficacy endpoint), and response on pain at rest, pain at movement, stiffness, tenderness, and movement restriction (as secondary efficacy endpoints), as well as the number of patients with drug-related adverse events (DRAEs) were meta-analytically evaluated using the Review Manager Software version 5.4.1. RESULTS: In total, 38 records were identified, but only two placebo-controlled studies (with 342 patients with mild to moderate acute muscle pain [55.3% female, age 50.6 ± 16.6 years], of whom 173 received PRI and 169 placebo, each as monotherapy) proved to be suitable for quantitative and qualitative analysis. Treatment with PRI was (irrespective of its mode of administration as oral tablet or intramuscular injection) associated with a significantly higher global response rate compared to placebo (74.0 vs. 49.7%; OR 2.86, 95%-CI: 1.82-4.51; p < .00001; Cohen´s h: 0.506, NNT: 4.1; Chi2 for heterogeneity 1.41 (p = .24], I2  = 29%), and significantly higher response rates were also found for all secondary efficacy endpoints. The safety of PRI was comparable to that of placebo: DRAEs were only seen in one of the two studies and reported for 13 vs. 10 patients (OR: 0.76 95%-CI: 0.32-18.1; p = .54, NNH: 62.6), and related discontinuations were reported for four vs. one patient (2.3 vs. 0.6%; p = .231). CONCLUSIONS: The results from this meta-analysis as based on two placebo-controlled studies in adult patients with mild to moderate acute muscle pain demonstrate that a 3-week monotherapy with PRI showed a comparable safety profile, but significantly better analgesic effects and improvements of related impairments such as stiffness, tenderness, and movement restrictions compared with placebo - irrespective of its mode of administration.

Muscle pain is one of the most common pain problems worldwide.In the majority of cases, muscle pain is temporary, transient, and benign in nature. However, people affected may still experience severe pain and significant pain-related disabilities in daily life activities that may require temporary drug treatment ­ also in order to be able to undertake the non-drug treatment measures necessary to prevent recurrence.Current treatment recommendations for muscle pain are largely ´non-specific´ and limited to symptomatic pain-relieving measures (e.g. non-steroidal anti-inflammatories), while muscle relaxants ­ such as pridinol (PRI), which has been reapproved in Germany in 2017 and first time approved in the United Kingdom, Spain, and Poland in 2020 ­ are currently not recommended (primarily due to insufficient efficacy data from controlled clinical trials) but nevertheless frequently prescribed.Due to our systematic literature research of double-blind randomized and placebo-controlled trials, a 3-week monotherapy with PRI vs. placebo proved to be comparably tolerated, but significantly more effective in patients with muscle pain ­ irrespective of the mode of administration (oral or as intramuscular injection).These outcomes confirm already available real-world evidence on the beneficial efficacy and tolerability of PRI in daily practice. However, more recent RCTs or numerically larger comparative real-world evidence analyses are needed to evaluate the efficacy of PRI in comparison to currently recommended first-line therapies for patients with muscle pain.

Localized peripheral neuropathic pain: topical treatment with lidocaine 700 mg medicated plaster in routine clinical practice.

Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700 mg medicated plaster (LMP) in localized peripheral neuropathic pain (l-PNP) treatment compared with first-line oral medications (OM). Patients & methods: This was a noninterventional, retrospective 6-month cohort study in patients refractory to at least one recommended OM, using anonymized medical care data from the German Pain eRegistry. Treatment groups were matched by propensity scoring, considering seven predefined confounding factors. The primary effectiveness end point was the absolute change in average pain intensity index from baseline at weeks 4, 12 and 24 of treatment and over the treatment period. Results: A total of 3081 datasets were retained per treatment group. LMP provided superior pain reductions and significantly greater improvements in pain-related impairments of daily living and quality of life with significantly better tolerability (p < 0.001 for all parameters) than OM. Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP for l-PNP treatment under routine medical care.

Conditions such as shingles, diabetes and surgery may lead to chronic localized neuropathic pain. This pain is often described as burning or stabbing and can limit functioning in daily activities and diminish quality of life. Several oral and topical medications are available for neuropathic pain treatment. The current study compared the effectiveness and tolerability of lidocaine 700 mg medicated plaster applied directly at the painful skin area with oral medications. Anonymized patient data collected in a German pain registry were selected based on predefined criteria (3081 patient data sets per treatment). Lidocaine plaster treatment resulted in superior pain relief, significantly fewer restrictions in daily life activities and better quality of life than the oral medications evaluated and was significantly better tolerated. This study showed that lidocaine 700 mg medicated plaster is effective and well tolerated in the treatment of chronic localized neuropathic pain in routine medical practice.

Lidocaine 700 mg medicated plaster for postherpetic neuralgia: real-world data from the German Pain e-Registry.

Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700 mg medicated plaster (LMP) compared with oral systemic first-line medications (OSM) in postherpetic neuralgia treatment. Patients & methods: Retrospective cohort study in patients refractory to at least one recommended OSM (single drug or a combination of drugs) using anonymized routine medical care data from the German Pain e-Registry. A matched pair approach using propensity score matching was employed. Results: A total of 1711 data sets of postherpetic neuralgia patients were identified per treatment group. The majority (>60%) had experienced pain for more than a year and reported a high burden of pain and reduced quality of life. Six months of LMP treatment provided significantly greater pain reductions, improvements in pain-related impairments and quality of life than OSM treatment (p < 0.001 for all parameters). Drug-related adverse events and treatment discontinuation due to drug-related adverse events also occurred less frequently under LMP treatment (p < 0.001). Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP under routine medical care. The treatment was significantly more effective when compared with first-line oral systemic medications.

Lay abstract Postherpetic neuralgia is the most common complication of shingles. It is a chronic condition causing burning pain that persists long after the shingles rash disappears. There are several oral and topical medications available for pain treatment. Our study compared the effectiveness and tolerability of the topical lidocaine 700 mg medicated plaster with oral medications using anonymized patient data from German clinical practices collected in a pain registry (1711 patient data sets per treatment). Six months of treatment with the lidocaine plaster resulted in better pain relief, fewer restrictions in daily life activities, and better quality of life for the patients than the oral medications investigated. The lidocaine plaster was also significantly better tolerated. The lidocaine 700 mg medicated plaster is effective and well tolerated in routine medical practice.

Tapentadol prolonged release in patients with chronic low back pain: real-world data from the German Pain eRegistry.

Aim: Comparison of tapentadol prolonged release (PR) with other oral WHO-III PR opioid analgesics (morphine, oxycodone ± naloxone, hydromorphone) in routine medical care of chronic low back pain. Patients & methods: Noninterventional, retrospective 12-week study using anonymized clinical practice data from the German Pain eRegistry. Six effectiveness, tolerability, and safety criteria were aggregated in a primary composite end point (treatment responder). Propensity scoring matched 2331 datasets per treatment cohort. Results: All six single criteria showed significantly better outcomes for tapentadol PR (all parameters p < 0.001). There were significantly more treatment responders under tapentadol PR (65.7 vs 14.2%; p < 0.001). Conclusion: Tapentadol PR showed significantly better effectiveness and tolerability in severe chronic low back pain unsuccessfully treated with WHO-I/II analgesics compared with the other oral WHO-III PR opioids investigated.

Lay abstract Chronic low back pain is a common condition often resulting in impaired functioning in daily life and reduced quality of life and well-being of the patient. In case treatment with less potent pain medications is unsuccessful, opioid treatment might be required. Our study compared the effectiveness and tolerability of the prolonged release formulation of the atypical opioid tapentadol with other strong opioids commonly used for chronic pain treatment in Germany (morphine, hydromorphone, oxycodone ± naloxone). Anonymized patient data from German clinical practices collected in a pain registry were used (2331 comparable patients per treatment group). Patients receiving 12 weeks of tapentadol treatment experienced significantly greater pain relief, greater improvements in daily living activities, sleep, and quality of life compared with those receiving the other strong opioids investigated. Neuropathic pain components (pain features resembling nerve pain, often described as shooting, burning or stabbing pain) were reduced to a greater extent in the tapentadol treatment group. Tapentadol was also significantly better tolerated. This study showed that tapentadol is effective and well tolerated in chronic low back pain treatment in routine medical practice in patients still in considerable pain despite treatment with less potent pain medications.

Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials.

OBJECTIVE: Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges' g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2). RESULTS: Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of -0.40 (95% confidence interval [CI]: -.59 to -.21; FE, P < .0001) or -0.44 (95% CI: -.70 to -.19; RE, P = .0006). A SMD of -0.21 (95% CI: -.32 to -.10; FE) or -0.26 (95% CI: -.42 to -.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses. CONCLUSIONS: Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.

A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain.

The 20% prevalence of chronic pain in the general population is a major health concern given the often profound associated impairment of daily activities, employment status, and health-related quality of life in sufferers. Resource utilization associated with chronic pain represents an enormous burden for healthcare systems. Although analgesia based on the World Health Organization's pain ladder continues to be the mainstay of chronic pain management, aside from chronic cancer pain or end-of-life care, prolonged use of non-steroidal anti-inflammatory drugs or opioids to manage chronic pain is rarely sustainable. As the endocannabinoid system is known to control pain at peripheral, spinal, and supraspinal levels, interest in medical use of cannabis is growing. A proprietary blend of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as the principal cannabinoids is formulated as an oromucosal spray (USAN name: nabiximols) and standardized to ensure quality, consistency and stability. This review examines evidence for THC:CBD oromucosal spray (nabiximols) in the management of chronic pain conditions. Cumulative evidence from clinical trials and an exploratory analysis of the German Pain e-Registry suggests that add-on THC:CBD oromucosal spray (nabiximols) may have a role in managing chronic neuropathic pain, although further precise clinical trials are required to draw definitive conclusions.

[Real-life efficacy and tolerability of methocarbamol in patients suffering from refractory muscle-related low/back pain - Results of a health care research project based on data from the German pain practice registry]. / Wirksamkeit und Verträglichkeit von Methocarbamol bei muskulär bedingten subakuten Kreuz-/Rückenschmerzen : Ergebnisse eines Versorgungsforschungsprojektes unter Verwendung von Daten des DGS-PraxisRegister Schmerz.

BACKGROUND: Subacute, muscle-related low/back pain (L/BP) is known to be difficult to treat and frequently requires more specific causal-oriented treatments with agents improving the increased muscle tone. Currently, only methocarbamol is approved and available for the 1st-line treatment of patients with muscle-related L/BP in Germany - however, without sufficient data on longer lasting effects (> 1 week) in elsewhere refractory patients. METHOD: Noninterventional cohort study, based on anonymized routine data of the German pain practice registry; retrospective evaluation of patients with refractory L/BP, who first time received a treatment with methocarbamol between October 1st until December 31st, 2015, and who documented their response to treatment with the standardized and validated instruments of the German pain questionnaire over at least 4 weeks (n = 251 patients). RESULTS: During the 4-week evaluation period, patients reported a highly significant and clinically relevant improvement of pain intensity (from 53.0 ± 10.5 to 19.0 ± 10.0 mm VAS), pain-related disability in daily life (mPDI: from 42.1 ± 12.5 to 15.5 ± 10.8) and quality of life (QLIP: from 18.6 ± 6.3 to 34.0 ± 5.5; all changes p < 0.001 vs. baseline). Corresponding 50% response rates were 81.7 (n = 205), 68.5 (n = 172) und 91.6 (n = 230) %. In parallel, lumbar mobility (measured with the Schober's test) improved from 10.7 ± 0.7 to 14.7 ± 0.7 cm (p < 0,001). Overall, seven patients recorded eight minor treatment-related adverse events, which all resolved spontaneously during treatment without any specific countermeasures. CONCLUSION: Under the conditions of daily life, patients with elsewhere refractory L/BP reported a significant and clinically relevant improvement of pain intensity, pain-related disability and quality of life in response to a 4-week treatment with methocarbamol.

[Transmucosal fentanyl administration: sublingual, buccal, nasal - all the same? Treatment of breakthrough cancer pain]. / Transmukosale Applikation von Fentanyl: sublingual, buccal, nasal ­ egal?

BACKGROUND: Transient exacerbation of pain in cancer patients (breakthrough cancer pain, BTCP) despite adequately controlled background pain should be regarded as an independent disease and receive targeted treatment. The opioid of choice is fentanyl, a rapid onset and highly potent WHO category III analgesic. Fentanyl has a strong first pass effect when administered orally and resorbed enterally, however it is well suited for transmucosal administration, e.g. on the oral or nasal mucosa. Seven different preparations of rapid onset fentanyl for transmucosal administration via various administration pathways are currently available in Germany. SCIENTIFIC PROBLEM AND METHOD: The aim of this review article was to determine which patient can benefit most from which forms of administration. Since there are hardly any direct comparisons of administration forms among each other, meta-analyses and reviews were included in the assessment. RESULTS AND CONCLUSION: Tablets with an applicator (lozenge), sublingual and buccal tablets, as well as a buccal film are available for the oral transmucosal administration of fentanyl; there is an aqueous fentanyl nasal spray and a pectin-rich nasal spray for nasal transmucosal administration. The individual preparations differ considerably with regard to their pharmacological (e.g. bioavailability, cmax and tmax) and patient-relevant parameters (e.g. onset of action, potency and duration of effect). Fentanyl nasal spray is superior to the other forms of administration in terms of rapid onset of action and clinically relevant pain reduction and can thus be recommended as a treatment option for rapidly evolving and/or spontaneously occurring breakthrough cancer pain.

Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study.

OBJECTIVE: To demonstrate non-inferior/superior efficacy of flupirtine modified release (MR) compared with tramadol/placebo for the management of moderate to severe chronic low back pain (LBP). RESEARCH DESIGN: Randomized, double-blind, active-/placebo-controlled double-dummy multicenter study, performed in 31 German study centers. LBP patients (n = 363) with moderate pain intensity were randomized 1:1:1 to receive flupirtine MR 400 mg, tramadol extended release (ER) 200 mg, or matching placebo (each given OD in the evening) over 4 weeks. CLINICAL TRIAL REGISTRATION: EudraCT 2009-013268-38. MAIN OUTCOME MEASURES: Primary endpoint was change from baseline in the LBP intensity index (LBPIX; 11-point NRS) at week 4; last observation carried forward was used to impute missing scores. RESULTS: Least square (LS) mean ± SD LBPIX changes from baseline at week 4 were clinically significant for all three treatment groups of the intent-to-treat (ITT) and the per-protocol (PP) population (n = 326/276): placebo (n = 110/96): -1.81 ± 1.65/-1.77 ± 1.59; flupirtine MR (n = 109/95): -2.23 ± 1.73/-2.28 ± 1.68; and tramadol ER (n = 107/85): -1.92 ± 1.84/2.03 ± 1.83 (p < 0.001 for each). ITT/PP treatment effects for flupirtine MR were non-inferior when compared with tramadol ER and superior when compared with placebo (p = 0.003/0.033). Significantly more ITT patients treated with flupirtine MR (59.6/37.6 showed a ≥30/50% LBPIX relief in comparison to placebo (46.4/24.6%; p vs. flupirtine MR: 0.049/0.037). Treatment contrasts for tramadol failed to reach significance vs. placebo. Within the safety population (n = 355), flupirtine MR (n = 119) was associated with a significantly lower incidence of treatment emergent AEs (TEAEs; 21.0%) and TEAE-related study discontinuations (3.4%) than tramadol ER (n = 116; 34.5/12.0%; p = 0.039/0.017) and exhibited an overall safety/tolerability profile non-inferior to placebo (n = 120; 15.8/3.3%; p = ns for each). Major limitations of this study were the short treatment duration, the comparison of different drug classes and the lack of a titration phase. CONCLUSIONS: The analgesic efficacy of flupirtine MR 400 mg OD was comparable to that of tramadol ER 200 mg OD and superior to that of placebo.

Low-dose 7-day transdermal buprenorphine in daily clinical practice - perceptions of elderly patients with moderate non-malignant chronic pain.

OBJECTIVE: To assess patients' perceptions regarding the low-dose 7-day buprenorphine transdermal patch for treatment of moderate non-malignant chronic pain. METHODS: Patient-reported outcome data were collected in clinical practices in Germany in a prospective, multicenter, non-interventional observation using the German Pain Questionnaire/German Pain Diary. Questionnaires were completed by the patients without influence from the attending physician. Mean change in pain intensity (lowest, average, and highest pain intensity in the previous 24 h), changes in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), in impairments of daily activities (modified pain disability index, mPDI), in quality of life (quality of life impairment by pain inventory, QLIP), and in overall burden of pain over a 12-week treatment period were evaluated. RESULTS: Data of 891 patients were assessed (mean age 72.8 years). Buprenorphine starting doses were mainly 5 µg/h (67.1% of patients) and 10 µg/h (27.3%). At the end of week 12, the majority received either 5 µg/h (41%) or 10 µg/h (42.3%) buprenorphine. Mean average pain intensity was reduced by 5.1 points to 1.7 ± 1.3 from 6.8 ± 1.5 points at baseline (76% improvement). Amelioration was observed in HADS-A (59% from 7.8 ± 3.3 at baseline) and HADS-D (56% from 9.2 ± 3.1), in mPDI sum score (76%; from 31.1 ± 9.8), and in quality of life (165%; from 13.9 ± 10.1). Mean burden of pain continuously decreased. LIMITATIONS: All those inherent in open-label observations and pain studies using subjective and patient-reported outcome parameters (such as the lack of a control group). CONCLUSIONS: Our results indicate that the 7-day buprenorphine patch might be considered an effective treatment option for moderate non-malignant chronic pain management in daily clinical practice. The mostly elderly patient population of this patient survey experienced sustained pain relief and improvements in pain-related impairments of daily activities and quality of life, leading to a substantial reduction in overall burden of pain.

Patient perceptions associated with the 5% lidocaine medicated plaster in daily practice.

OBJECTIVE: To evaluate patients' perceptions of 5% lidocaine medicated plaster for treatment of chronic neuropathic pain in daily clinical practice. RESEARCH DESIGN AND METHODS: In a prospective, multicentre, non-interventional observation, patient-reported outcome data were collected in clinical practices in Germany using the German Pain Questionnaire for pre-treatment documentation and the German Pain Diary for documentation of weekly treatment-associated changes. Questionnaires were completed by the patients without input from their physicians. MAIN OUTCOME MEASURES: Mean changes over the 12-week treatment period in pain intensity, in impairments of daily activities (modified pain disability index, mPDI) and of quality of life (quality of life impairment by pain inventory, QLIP), in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), and in overall burden of pain. RESULTS: Data of 922 patients were evaluated. Mean average pain intensity over 24 h improved by 5.1 points (74%) from 6.9 ± 1.6 points at baseline. A 30% reduction in overall pain intensity was already observed within the first 2-3 weeks with continuous further reductions until end of observation. Marked improvements in anxiety and depression scores (40% and 52%, respectively), and in pain-related restrictions in daily life activities (66%) and quality of life (157%) were also noted. Burden of pain was reduced by 56.2 points (73%) from 77.5 points at baseline. Stratification by diagnosis showed a treatment effect of lidocaine plaster for all underlying conditions with highest treatment effects for diabetic polyneuropathy and postherpetic neuralgia. CONCLUSIONS: In a patient population where 46% of individuals already suffered from chronic to markedly chronic pain, patients perceive the 5% lidocaine medicated plaster as an efficacious topical treatment of chronic neuropathic pain in daily clinical practice. Strongest pain relief as well as associated improvements in pain-related restrictions were observed within the first five treatment weeks; however, beneficial effects continued until end of observation.

Sublingual fentanyl orally disintegrating tablet in daily practice: efficacy, safety and tolerability in patients with breakthrough cancer pain.

BACKGROUND AND OBJECTIVES: Breakthrough cancer pain (BTcP) affects more than half of patients with cancer pain and has severe detrimental impacts on quality of life (QoL). This study evaluated the efficacy, QoL impact and safety of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in a clinical setting. RESEARCH DESIGN AND METHODS: This was a prospective, multi-center phase IV study. Opioid-tolerant adult patients with BTcP received sublingual fentanyl ODT in the course of routine clinical practice, and completed questionnaires over a 28-day observation period. Efficacy was assessed using measures of maximum BTcP intensity and the times to first effect and maximum effect of sublingual fentanyl ODT. Changes in QoL were evaluated using the modified pain disability index (mPDI) and the hospital anxiety and depression scale (HADS). Adverse events were recorded throughout. RESULTS: Of 217 enrolled patients, 181 (83.4%) completed the observation period. During the study, 3163 episodes were treated with a mean dose of 401.4 µg per episode. The study recorded a significant improvement in maximum BTcP intensity with sublingual fentanyl ODT, compared with baseline (p < 0.0001). Patients reported experiencing the first effects of the study drug within 5 minutes of administration in 67.7% of episodes, and maximum effect within 30 minutes in 63.2% of episodes. mPDI and HADS scores significantly improved during the observation period (p < 0.0001). Sublingual fentanyl ODT was well-tolerated, with 12 patients (5.5%) experiencing ≥1 study drug-related adverse event. Study limitations include a modest size and duration, and the single-arm design. CONCLUSIONS: Under the conditions of a phase IV study, sublingual fentanyl ODT was effective and well-tolerated for the treatment of BTcP in opioid-tolerant cancer patients. Study treatment was associated with significant improvements in BTcP intensity and QoL scores, and patients reported rapid onset of action in the majority of episodes.

Dysport® for the treatment of myofascial back pain: Results from an open-label, Phase II, randomized, multicenter, dose-ranging study.

Background and purpose Botulinum toxin type A (BoNT-A) has antinociceptive and muscle-relaxant properties. The objectives of this study were to investigate the efficacy and safety of a single BoNT-A (Dysport®) treatment in myofascial back pain. Methods In this randomized, open-label, multicenter study, adults with myofascial lower back pain received Dysport® injections at four trigger points (60,80 or 120 units per injection point). Patients were followed for 12 weeks. The a priori primary endpoint was a pooled evaluation, at Week 6, of seven measures of efficacy, including pain intensity (patient diary), modified Pain Disability Index (PDI) score, use of interfering concomitant analgesics, and patient-rated global efficacy. Optional assessments of pressure thresholds and tissue compliance were conducted. Safety was also assessed. Results A total of 202 patients were randomized to treatment and 189 patients received a low (n = 57), medium (n = 57), or high (n = 75) total dose of Dysport® at 34 centers in Germany between October 2002 and October 2003. All treated patients were included in the safety population; 8 patients were excluded from the intention-to-treat population. Patients had moderate to severe pain at baseline. At baseline, 120 patients were receiving concomitant analgesic therapy; 6.7%, 74.2% and 19.2% were considered to cause mild, moderate and severe interference with pain measurements, respectively. There was no difference between doses for the a priori combined primary endpoint. Patient-reported pain intensity scores at rest and on movement decreased significantly after treatment for all groups combined (p < 0.0001 at all visits). At Week 6, reductions in pain intensity at rest were 29%, 19% and 26% for the low-, medium- and high-dose groups, respectively; reductions in pain intensity on movement were 27%, 18% and 26%, respectively. Overall, patients who reported pain intensity reductions at Week 6 were evident within 3 weeks of treatment and were maintained for the 12 weeks of the study. In the total population, significant decreases in mean PDI sum scores from baseline were observed from Week 3 and were maintained through to the end of treatment (Week 12); no differences between the dose groups were observed. Pressure thresholds and tissue compliance also increased during the study. Adverse events were generally as expected for BoNT-A; the majority were mild or moderate in severity. Conclusions Dysport® treatment was associated with reductions in myofascial back pain and was well tolerated. Nodose-response relationship was observed; treatment with Dysport® using a four-trigger-point injection protocol at 60 units per trigger point was associated with a clinically relevant and statistically significant improvement in pain and pain-related disability; there was no additional benefit from the higher doses. Implications Our findings are limited by the lack of a control group and further research is warranted to confirm the value of Dysport® for the treatment of myofascial back pain and confirm the optimum dosing in this indication.