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.

Lidocaine medicated plaster, an additional potential treatment option for localized post-surgical neuropathic pain: efficacy and safety results of a randomized, placebo-controlled trial.

OBJECTIVE: To assess the efficacy and safety of lidocaine 700 mg medicated plaster (lidocaine plaster) compared to placebo in patients with moderate to severe chronic post-surgical neuropathic pain (PSNP). METHODS: Patients (n = 363) with a diagnosis of PSNP for a minimum of 3 months to 36 months were randomized (1:1) to lidocaine plaster or placebo for a 12 week double-blind treatment period. Randomization was stratified as "plaster-only" (no concomitant medication for PSNP) or as "add-on" (stable systemic medication for PSNP). The primary efficacy endpoint was the change from baseline in 24 hour average pain intensity at Week 12, assessed by 11 point numerical rating scale (NRS). The trial was registered in ClinicalTrials.gov (NCT01752322) and EudraCT (2012-000347-28). RESULTS: Treatment with lidocaine or placebo plaster led to a clinically relevant reduction in average pain intensity. Pain reduction (least squares mean [LS mean] standard error [SE], [95% confidence interval, CI]) with lidocaine plaster (-1.70 [0.16], [-2.03, -1.38]) was numerically higher than with placebo (-1.47 [0.16], [-1.78, -1.15]) but the difference was not statistically significant (-0.23 [0.23], [-0.69, 0.22]). Pre-specified exploratory subgroup analyses showed the largest differentiation between lidocaine and placebo in patients without concomitant pain medication, and in patients with more than 1 year between surgery and enrollment. Many secondary outcomes showed a numerically larger improvement in favor of lidocaine. The most commonly reported adverse events were administration site reactions linked to topical administration. CONCLUSIONS: A clinically relevant pain reduction was observed with lidocaine plaster in patients with PSNP. The safety and tolerability profile is consistent with current knowledge.

Treatment of postherpetic neuralgia with 5% lidocaine medicated plaster in elderly patients - subgroup analyses from three European clinical trials.

OBJECTIVE: To investigate short- and long-term effectiveness and safety of the 5% lidocaine medicated plaster in the treatment of postherpetic neuralgia (PHN) in elderly patients (≥70 years of age). METHODS: Data from three European clinical trials was compared after stratification according to age (<70 years and ≥70 years). Length of study phase investigated was 4 weeks for study 1, 8 weeks for study 2, and up to 12 months for study 3. Effectiveness outcome measures were pain intensity, pain relief, allodynia severity, Clinical Global Impression of Change, and Patient Global Impression of Change. Safety was assessed by adverse event documentation. RESULTS: Mean average pain intensity improved in the elderly by -2.1 (SD 2.1) vs. -2.5 (SD 2.0) for <70 year old patients after 4 weeks, by -1.4 (SD 1.8) vs. -1.7 (SD 1.3) after 8 weeks, and by -1.5 (SD 1.9) vs. -2.7 (SD 2.2) after 12 months. Most patients presented with allodynia (>85% of elderly, >78% of younger patients) which was described by >51% as painful or extremely painful. Allodynia severity was markedly reduced in both groups during all three trials. Drug-related adverse events occurred in <20% of elderly and <15% of <70 year old patients and were mainly skin related. CONCLUSIONS: The 5% lidocaine medicated plaster provided pain relief and marked reductions in allodynia severity in elderly PHN patients with an excellent safety profile under short- and long-term treatment supporting the addition of the plaster to the treatment armamentarium for this age group. STUDY LIMITATIONS: All analyzed study phases were open-label and lacking a placebo control group.

Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia.

OBJECTIVE: Prospective evaluation of the long-term efficacy and safety of the 5% lidocaine medicated plaster in patients with post-herpetic neuralgia (PHN). RESEARCH DESIGN AND METHODS: Patients with persisting pain for ≥3 months after acute herpes zoster and a baseline pain intensity of at least 4 on an 11-point numerical rating scale (NRS 0-10) were treated with 5% lidocaine medicated plasters for up to 5 years and monitored in regular intervals. Efficacy parameters are presented for the first 4 years and include patients' recall of pain relief (6-point verbal rating scale (VRS), clinical global impression of change (CGIC), patients' global impression of change PGIC), and the global evaluations of study medication. Safety parameters (clinical examination, skin evaluation, laboratory) and adverse events (AEs) were assessed at regular visits. CLINICAL TRIAL REGISTRATION: KF10004/02. RESULTS: A total of 102 patients continuing from a 1 year main study period were included in an extension phase of up to 3 years. Ten patients (9.8%) dropped out due to lack of efficacy and 9 patients (8.8%) due to treatment-related AEs; 56 patients (54.9%) left the study for non-treatment-related reasons. Twenty-seven patients (26.4%) were still under treatment after a total treatment period of 4 years. On average, a pain relief of at least 4.3 (between moderate and a lot) was achieved throughout the study. At all visits the CGIC and the PGIC were much or very much improved in about 80% of patients. At the final visit, study medication was rated at least to be good by 91% of physicians and 89% of patients. Drug-related adverse events (DRAEs) were reported in 19 of 102 patients, mainly mild to moderate localized skin reactions. There were no hints for a reduced analgesic effect or an increase of DRAEs with long-term treatment. CONCLUSIONS: This study demonstrates that long-term treatment of ≥12 months with the 5% lidocaine medicated plaster is effective and well tolerated in PHN patients. These findings support the recommendations to use the 5% lidocaine medicated plaster as baseline therapy for localized neuropathic pain after herpes zoster infection (PHN).

The incidence and outcome of severe brain trauma - Design and first results of an epidemiological study in an urban area.

Epidemiological data on the incidence, the prehospital and hospital care and the outcome of traumatic brain injury in Germany are scarce. It is therefore difficult to estimate the importance of this injury with respect to magnitude as well as effectiveness and efficiency of therapeutic concepts. We therefore planned a study that was supposed to provide population based epidemiological data in the field of severe brain trauma from the site of the accident until discharge from hospital. All 90.000 prehospital emergencies that were cared for by emergency physicians in Cologne from January 1990 until December 1996 were screened for identification of severe brain trauma. Their clinical course was reviewed using standard records and patients were included if they had their accident within the city of Cologne and fullfilled the final inclusion criteria of GCS /=3. 650 eligible patients were identified of whom 530 had complete datasets (follow-up 80 %). Univariate statistical analysis was performed for all relevant variables. The main study endpoints were incidence and outcome of severe brain trauma. The annual incidence of severe brain trauma in Cologne (1 mio. inhabitants) was 93. The average age was 39 years and 71 % of the patients were male. The average prehospital GCS was 6.8, the average prehospital Trauma Score was 8.3 points. 49 % of the study population suffered from multiple injuries. The overall mortality rate was 46,6 %. 60 % of deaths occurred within the prehospital setting. The incidence of severe brain trauma in Cologne in this study was significantly lower compared to what could be expected from the litera-ture. The overall mortality was high, especially the high prehospital death rate is striking.