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.

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.

Comparative Benefit-Risk Assessment for Lidocaine 700 mg Medicated Plaster and Pregabalin in Peripheral Neuropathic Pain Following a Structured Framework Approach.

INTRODUCTION: Peripheral neuropathic pain (PNP) is difficult to treat. Several oral drugs are recommended as first-line treatments. Nevertheless, many patients cannot obtain sufficient pain relief or do not tolerate systemically active treatments. Topical treatments, with a lower risk of systemic side effects such as lidocaine 700 mg medicated plaster, are also recommended in treatment guidelines. This analysis compares the benefit-risk balance of topical 700 mg lidocaine medicated plaster with the benefit-risk balance of oral pregabalin administration for the treatment of PNP following current recommendations on benefit-risk assessment (BRA) methodology. METHODS: The Benefit-Risk Action Team (BRAT) framework was used as structured approach. Selection of key benefits and risks was supported by a patient survey. Published randomized controlled clinical trials were the main source to identify data related to key benefits and risks. The outcome of randomized clinical trials was compared with real-world evidence (RWE) data for consistency. RESULTS: Identified key benefits were pain reduction and improvement in quality of life. Key risks identified were application site reactions, dizziness, confusion, weight gain, peripheral edema, and blurred vision. Overall, there was similarity in key benefits between the comparators; however, a clear advantage regarding key risks in favor of lidocaine 700 mg medicated plaster was observed. This observation was consistent across data from a direct comparison trial, randomized placebo-controlled trials, as well as data from RWE studies. The low number of randomized controlled trials for lidocaine 700 mg medicated plaster was the main limitation. CONCLUSION: Guided by the opinion of patients regarding key benefits and risks deemed important for treatments of peripheral neuropathic pain, our analysis showed that lidocaine 700 mg medicated plaster has a more favorable benefit-risk balance compared to pregabalin (300 and 600 mg daily).

Systematic review and network meta-analysis of the efficacy and safety of lidocaine 700 mg medicated plaster vs. pregabalin.

Objective: Neuropathic pain prevalence is estimated between 7% and 10% of the population. International guidelines recommend a variety of drugs at different therapy lines for pain relief. However, side effect profiles, for example, prompted the UK government recently to classify pregabalin and gabapentin as class C drugs. Lidocaine 700 mg medicated plaster (LMP) might be a safer alternative. A systematic review assessed how LMP and pregabalin compared in terms of efficacy and safety. The review focused on pain reduction, quality of life and adverse events in peripheral neuropathic pain (PNP) i.e. post-herpetic neuralgia, diabetic peripheral neuropathy, post-surgical/trauma, or other PNP conditions.Methods: Electronic databases were searched as well as a number of other sources up to November 2018. Sensitive strategies were used, with no restriction by language or publication status. Two independent reviewers screened records and extracted data with consensus determining final decisions. Risk of bias was assessed using the Cochrane Collaboration 2011 checklist for RCTs. Full network meta-analysis was conducted to compare LMP to pregabalin 300/600 mg in terms of pain reduction, quality of life, as well as serious adverse events and selected adverse events. Trials with enriched enrolment design were excluded.Results: Searches retrieved 7,104 records. In total 111 references pertaining to 43 RCTs were included for data extraction. Bayesian network meta-analysis of several pain outcomes showed no clear difference in efficacy between treatments However, LMP was clearly advantageous in terms of dizziness and any adverse event vs. pregabalin 600 mg/day and discontinuations vs. pregabalin 300 mg/day or 600 mg/day, as well as being associated with improved quality of life (albeit in this case based on weak evidence).Conclusions: LMP was found to be similar to pregabalin in reducing pain in all populations but had a better adverse events profile.

Cebranopadol, a Novel First-in-Class Analgesic Drug Candidate: First Experience With Cancer-Related Pain for up to 26 Weeks.

CONTEXT: Pain is one of the most prevalent symptoms associated with cancer. Strong opioids are commonly used in the analgesic management of the disease, but carry the risk of severe side effects. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. For cancer patients, frequently experiencing multimorbidities and often exposed to polypharmacy, cebranopadol is easy to handle given its once-daily dosing, the small tablet size that enables swallowing, and the option to flexibly titrate to an effective dose. OBJECTIVES: We assessed the safety and tolerability of prolonged treatment with oral cebranopadol for up to 26 weeks in patients suffering from chronic moderate-to-severe cancer-related pain. METHODS: This was a non-randomized, multi-site, open-label, single-arm clinical trial with patients who had completed a double-blind trial comparing morphine prolonged release with cebranopadol. In this extension trial, patients were treated with oral cebranopadol for up to 26 weeks. RESULTS: Cebranopadol was safe and well tolerated in patients with chronic moderate-to-severe pain related to cancer in the dose range tested (200-1000 µg once daily). The median and mean pain levels remained in the range of mild pain during the treatment period. CONCLUSION: Our data suggest that cebranopadol was safe and well tolerated when administered for up to 26 weeks in patients with chronic cancer-related pain who were previously treated with cebranopadol or morphine prolonged release.