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 prospective, randomized, controlled, double-blind, multi-center study to evaluate the efficacy and safety of a blue light device for the treatment of chronic back pain.

Introduction: Chronic back pain is one of the most prevalent conditions and has a large socio-economic impact. The lack of routine use of non-pharmacological options and issues associated with pharmacological treatments underscore high unmet needs in the treatment of back pain. Although blue light phototherapy has proven efficacy in dermatology, limited information is available about its use in back pain. Methods: In this proof-of-concept, randomized controlled trial, a pain relief patch (PRP) delivered blue light at the site of back pain for 30 min during five treatment sessions. The comparator device delivered green light for 5 s but was worn for 30 min. A follow-up visit took place after the last treatment. The primary objective was to demonstrate the superiority of treatment by PRP, compared to the control device, in reducing pain intensity at the end of the treatment period. The post-treatment visual analog scale (VAS) pain intensity score for each group was calculated across the five treatment sessions and compared to the baseline. Secondary objectives included the disability score (Roland-Morris Disability Questionnaire) and safety. Results: The full analysis set included 171 patients. A statistically significant reduction in pain intensity occurred after the use of PRP (p < 0.02), but the study did not meet its primary objective of a superiority trial aimed at demonstrating a 0.6 cm difference in favor of PRP on the VAS scale. There was no significant change in the disability scores. Subgroup analyses were performed to identify the treatment response by patient characteristics such as pain intensity at baseline and skin type. As expected, safety data showed erythema and skin discoloration in the PRP group but not in the control group. Discussion/conclusion: This trial had multiple limitations that need to be addressed in future research. Although the primary objective was not achieved, this proof-of-concept study provides important efficacy and safety data in relation to the use of blue light in the treatment of chronic back pain and key insights that may support further research on similar devices. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01528332.

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.

Painful diabetic peripheral neuropathy: real-world comparison between topical treatment with lidocaine 700 mg medicated plaster and oral treatments.

INTRODUCTION: Painful diabetic peripheral neuropathy (PDPN), a common complication of diabetes mellitus, is challenging to treat. Efficacy and tolerability of the topical lidocaine 700 mg medicated plaster (LMP) and well-established first-line oral medications (OM) were compared in refractory PDPN patients. RESEARCH DESIGN AND METHODS: This is a subgroup analysis of a non-interventional, retrospective 24-week cohort study using anonymized routine medical care data from the German Pain eRegistry. Propensity score matching provided 732 datasets per treatment group. Primary effectiveness endpoint was the absolute change in average 24-hour Pain Intensity Index (0-100 mm) from baseline after 4, 12 and 24 weeks of treatment and over the entire treatment period. RESULTS: The majority of this multimorbid and polymedicated study population of patients with PDPN had suffered pain for more than a year and presented with a high pain burden despite a median of seven previous analgesic medications. LMP treatment resulted in significant reductions in pain intensity and improvements in daily functioning already after 4 treatment weeks. Effectiveness was maintained over the treatment period even when concomitant analgesics were reduced or discontinued and quality of life improved. Mean change in the primary effectiveness parameter over the 24-week treatment period was -30.2 mm (SE 0.38) and -17.0 mm (SE 0.51) in the LMP and OM groups, respectively. Improvements in all effectiveness parameters were significantly greater under LMP than under OM treatment (p<0.001). Significantly fewer patients under LMP than OM experienced drug-related adverse events (DRAEs; 9.6% vs 61.6%, p<0.001) and discontinued treatment due to DRAEs (4.4% vs 35.8%, p<0.001). CONCLUSIONS: LMP was effective and well tolerated in routine clinical care of patients with PDPN. The more favorable benefit/risk profile and greater reduction in intake of concomitant analgesics compared with OM suggest LMP as a useful treatment option for PDPN. TRIAL REGISTRATION NUMBER: EUPAS 32826.

Postsurgical neuropathic pain: lidocaine 700 mg medicated plaster or oral treatments in clinical practice.

Aim: To compare the effectiveness and tolerability of the lidocaine 700 mg medicated plaster (LMP) and oral first-line medications (OM) for the treatment of postsurgical neuropathic pain (PSNP) in routine clinical practice. Patients & methods: Data from a noninterventional, retrospective 24-week cohort study in patients with localized peripheral NP refractory to at least one recommended OM using anonymized German Pain eRegistry data were retrieved. A subgroup analysis was conducted on 531 datasets of PSNP patients. Results: Pain relief, improvements in pain-related impairments of daily living and quality of life, and tolerability were significantly greater under LMP than under OM (p < 0.001 for all parameters). Conclusion: These real-world data show the effectiveness and good tolerability of LMP for PSNP treatment in routine clinical practice.

Surgical procedures may lead to chronic postsurgical neuropathic pain often described as burning or shooting pain. This pain can be treated with medications that are swallowed (oral) or applied to the skin (topical). Our study compared the effectiveness and tolerability of the topical lidocaine 700 mg medicated plaster with oral medications in 531 anonymized patient data sets from a German pain registry. Patients on the lidocaine 700 mg medicated plaster had significantly better pain relief, significantly lower impact of pain on activities of daily life and quality of life and tolerated their treatment significantly better than those on oral medications. The lidocaine 700 mg medicated plaster can be considered as an alternative effective and well-tolerated treatment option for postsurgical neuropathic pain in routine clinical practice.

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.

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.

Severe chronic low back pain: patient journey from onset of symptoms to strong opioid treatments in Europe.

Aim: We report the first patient roadmap in severe chronic low back pain (cLBP) in Europe, assessing the views of cLBP patients and general practitioners (GPs) who treat cLBP with regard to current cLBP management. Methodology: Patient journey mapping was conducted in four European countries to assess the views of cLBP patients (n = 20) and GPs (n = 40). Results: Four broad phases of cLBP, subdivided into eight individual steps, were identified as part of the patient journey, showing a disconnect between patients' and physicians' treatment goals, and expectations regarding pain relief levels for some patients. Conclusion: Improved communication, with greater involvement of patients in multimodal management decisions, might benefit the GP-patient relationship and overall outcomes for cLBP patients.

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.

Rapid acting fentanyl formulations in breakthrough pain in cancer. Drug selection by means of the System of Objectified Judgement Analysis.

Drug selection of rapid acting fentanyl formulations in the treatment of breakthrough pain in patients with cancer is performed by the System of Objectified Judgement Analysis method. All seven available formulations were included in the analysis. The following selection criteria were used: number of available strengths, variability in the rate of absorption, interactions, clinical efficacy, side effects, ease of administration and documentation. No direct double-blind comparative studies between two or more formulations were identified and the clinical documentation of all formulations is limited. The most distinguishing criterion was ease of use. This led to slightly higher scores for Abstral, Instanyl and PecFent than for the other formulations. The pros and cons of each formulation should be discussed with the patient, and the most suitable formulation selected for each individual patient.