A targeted literature review of the burden of illness for spine-related neuropathic pain in Japan.

BACKGROUND: Neuropathic pain (NeP) is pain provoked by damage or disease in the nervous system and about one in three Japanese patients with spinal disorders are highly likely to have NeP. The humanistic and economic burden of illness (BOI) of spine-related NeP represents unmet medical needs that should be addressed. The purpose of this targeted literature review was to synthesize the available evidence on the BOI of spine-related NeP in Japanese patients. METHODS: PubMed and ICHUSHI were searched for relevant studies published between January 2010 and December 2020, in English or Japanese. The population included patients with one or more of prespecified spinal disorders and NeP, and outcomes of interest were data related to humanistic or economic burden. RESULTS: Out of 32 studies that assessed the BOI of spine-related disorders in Japan, only six specifically assessed spine-related NeP. Among these studies, five different validated questionnaires were used to measure humanistic burden. Spine-related NeP was consistently shown to be related with a poorer health-related quality of life and higher levels of anxiety and depression compared to the general population as well as patients with nociceptive pain. No articles directly evaluating economic burden were identified in this search, so an exploratory analysis was conducted. Reduction in work productivity by people experiencing spine-related NeP in the whole of Japan were estimated to total JPY 172,266,780,480 per year. CONCLUSIONS: The humanistic burden of spine-related NeP on Japanese patients is considerable, not only physically but also mentally. Exploratory analysis of the economic burden illustrates the possibility of substantial societal costs associated with NeP. In order to better understand the depth of BOI and the unmet medical need caused by spine-related NeP, further studies on real-world outcomes are recommended.

A large-scale database study for the prescription status of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, in Japan.

BACKGROUND: A new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, was first approved for treating peripheral neuropathic pain in Japan in 2019. This is the first report on the prescription status of mirogabalin using a large-scale prescription database. RESEARCH DESIGN AND METHODS: The authors analyzed the prescription data of 12,924 patients prescribed mirogabalin between 1 June and 31 August 2020. The endpoints were the number of patients prescribed, prescription days, prescription doses, dose changes, co-prescription patterns, medication possession ratio (MPR), and treatment discontinuation rates (TDRs). RESULTS: Mirogabalin was newly prescribed to 7,914 patients in the 3-month study period. Most patients were prescribed mirogabalin at about 10 mg/day during the study period, and 30.9% of patients were prescribed ≥ 20 mg/day on Day 90 after the first prescription. The most frequently prescribed concomitant drug was celecoxib. The MPR (80 to 110%) was 86.2%, indicating good treatment adherence. The cumulative TDRs during ≤ 7 Days, Days 31-60, and 61-90 were 14.0%, 70.0%, and 77.9%, respectively. CONCLUSIONS: Mirogabalin was prescribed to a considerable number of patients. These results may be useful for optimizing mirogabalin use for patients with peripheral neuropathic pain in daily clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000042592.

A review of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, for the treatment of peripheral neuropathic pain.

INTRODUCTION: Neuropathic pain (NeP) is a chronic and refractory condition in many patients, and its treatment is a challenge for physicians. A new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, has a high specific binding affinity for the α2δ subunit, with a slower dissociation rate for α2δ-1 than α2δ-2 compared to that of pregabalin. Mirogabalin was shown to be effective in NeP animal models, with a margin of safety between central nervous system side effects and the analgesic effect of the dose. It exerted a favorable analgesic effect, was well tolerated in patients with peripheral NeP (P-NeP), and was first approved in Japan in 2019 and subsequently in Korea and Taiwan in 2020. AREAS COVERED: The purpose of this article is to review the pharmacological characteristics, pharmacokinetics, and efficacy and safety of mirogabalin for NeP based on the results of non-clinical and clinical studies. EXPERT OPINION: Although there are several first-line therapies for NeP, insufficient efficacy and adverse drug reactions of NeP drugs often cause patient dissatisfaction. Mirogabalin was effective and well tolerated with a step-wise dose increase in clinical studies on P-NeP patients. Thus, mirogabalin is expected to be a useful treatment option for patients with P-NeP.

A Cross-Sectional Web Survey of Satisfaction with Treatment for Pain in Participants with Suspected Diabetic Peripheral Neuropathic Pain in Both Feet.

INTRODUCTION: Diabetic peripheral neuropathic pain (DPNP), a symptom of diabetic polyneuropathy (DPN), is underdiagnosed in people with diabetes. To date, no studies have determined the relationship between diagnosis of DPN and satisfaction with treatment for pain. Additionally, the factors that influence satisfaction with treatment for pain remain unknown. This questionnaire study was conducted to understand satisfaction with treatment for pain among participants with diabetes who experienced bilateral pain or numbness in their feet. METHODS: This cross-sectional, observational, web-based questionnaire study for participants with diabetes and suspected DPNP was conducted in Japan. Potential respondents were registered in the INTAGE Disease Panel or the Rakuten Insight Disease Panel. The primary endpoint was the number and percentage of participants who were satisfied with their DPNP treatment. Secondary endpoints included participant opinions regarding treatment-related efficacy, side effects, and economic burden, and factors affecting satisfaction with treatment. RESULTS: The questionnaire was accessed by 7565 potential participants; 777 met the eligibility criteria (final analysis set). Satisfaction with treatment for bilateral foot pain was low (satisfied, 27.9%; neither satisfied nor unsatisfied, 42.2%; unsatisfied, 23.4%; very unsatisfied, 6.4%). Participants were somewhat more satisfied with treatment side effects than with treatment efficacy and economic burden. Satisfaction with treatment mainly differed by improvement in actions in daily life, improvement in quality of life, and communication with doctors. The diagnostic testing rate for DPN was low, and diagnosis was more common in participants who complained of symptoms of pain and numbness (any visit) versus those who did not. CONCLUSION: Participants with diabetes who experience bilateral foot pain or numbness reported a low level of satisfaction with treatment for pain.

People with diabetes may develop diabetic polyneuropathy and experience diabetic peripheral neuropathic pain, which is often felt as pain or numbness below the knee. This study aimed to learn whether participants with diabetes who had pain or numbness in both feet were satisfied with the pain treatment they received. Factors affecting satisfaction with treatment were also evaluated. Potential participants with diabetes identified from two commercial databases (INTAGE Disease Panel or Rakuten Insight Disease Panel) of patients with various diseases living in Japan were asked to respond to our web survey. Besides satisfaction with treatment for pain, participants were asked about how well their treatment was working, treatment side effects, how treatment affected them financially, and what factors affected their satisfaction with treatment. The main finding was that only 27.9% of participants were satisfied with their treatment for foot pain and numbness. Generally, participants were more satisfied with treatment side effects than they were with how well the treatment worked, and how treatment affected them financially. Participants were more satisfied if they had an improved ability to perform everyday activities or experienced an improvement in quality of life with treatment. Participants were also more satisfied if they communicated well with their physician. The rate of diagnostic tests was low; however, participants were more likely to receive a diagnostic test when they complained of pain or numbness than when they did not. On the basis of these findings, we think improvements in the treatment of foot pain or numbness in those with diabetes are needed.

A Cross-sectional Survey of Patients with Suspected Diabetic Peripheral Neuropathic Pain in Japan.

Objective The burden of diabetic peripheral neuropathic pain (DPNP) is poorly understood. The present study reported on the current status of DPNP in Japan, to improve our understanding of this condition among healthcare providers and inform future clinical research on its prevalence, diagnosis, and management. Methods A cross-sectional, observational study (UMIN000037023) was conducted via a web-based survey. The primary endpoints were the frequency of patients with bilateral foot symptoms, consulting a doctor, understanding DPNP, and reporting problems in daily life, as well as the treatment awareness of patients. Patients Adults ≥20 years old who were registered in the Rakuten Insight Disease Panel and receiving anti-diabetic therapy in Japan were included. Results Bilateral foot pain symptoms were reported by 1,768/7,754 (22.8%) respondents, most commonly intense numbness (13.0%). Of those with symptoms, 55.3% consulted a doctor; the most common reason for not seeking consultation was feeling that symptoms were insufficiently severe to bother their doctor (89.4%). Nearly 60% reported understanding the causes of their symptoms, with diabetes-associated neurologic deficits (58.8%) most commonly identified. About one-quarter reported daily life problems, including an inability to walk for long periods (58.3%) and feeling anxious (58.1%). Treatment awareness was reported by 18.2%; oral medications were commonly recognized (64.6%). Conclusion In Japan, 22.8% of patients with diabetes have bilateral foot pain symptoms; some experience problems in their daily life without understanding the causes of their symptoms. This supports the importance of actions to increase awareness and minimize DPNP-associated impairment of daily life in patients with diabetes.

Cross-sectional study of patient satisfaction with oral analgesics in patients with chronic pain in Japan.

BACKGROUND: Chronic pain is often difficult to treat, and many patients are not satisfied with analgesic treatment. The authors assessed patient satisfaction with oral analgesics in patients with chronic pain in Japan. RESEARCH DESIGN AND METHODS: This was an observational cross-sectional study conducted in dispensing pharmacies. A patient satisfaction questionnaire survey was conducted in 781 patients prescribed one nonsteroidal anti-inflammatory drug (NSAID) or neuropathic pain (NeP) drug for at least 90 consecutive days. The primary endpoint was patient satisfaction with analgesics. The secondary endpoints were pain relief, activity of daily living (ADL) improvement and doctor-patient communication. RESULTS: The proportions of patients who answered 'satisfied if anything' or better for patient satisfaction in the NSAID and NeP drug groups were 70.0% and 65.2%, respectively, whereas those of patients who answered 'satisfied' were 43.3% and 29.4%, respectively. The proportions of patients with improved pain relief, ADL improvement, and good doctor-patient communication were numerically higher than those of patients who answered 'satisfied if anything' or better. CONCLUSIONS: Approximately two-thirds of the patients were satisfied with current analgesics. Patient satisfaction with oral analgesics could be influenced by multiple factors. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000036456.

Muraminomicins, novel ester derivatives: in vitro and in vivo antistaphylococcal activity.

Novel muraminomicin derivatives with antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) were synthesized by esterification of the hydroxy group on the diazepanone ring of muraminomicin Z1. Compound 1b (DS14450354) possessed a diheptoxybenzyl-ß-Alanyl-ß-Alanyl group and exhibited minimum inhibitory concentrations (MICs) against MRSA comparable to those against methicillin-susceptible S. aureus (MSSA). The MICs that inhibited 50 and 90% of the strains were 1 and 2 µg/mL, respectively. Compound 1a (DS60182922) possessed an aminoethylbenzoyldodecylglycyl moiety and showed bactericidal activity against MSSA Smith. The bactericidal activity of 1a against MRSA 10925 was comparatively lower, whilst 1b exhibited dose-dependent bactericidal activity against MRSA 10925. The mutation frequency of 1b was lower than that of 1a. An amino acid substitution (F226I) was observed in MraY mutants isolated from culture plates containing 1a or 1b. Subcutaneous 1a and 1b administration showed good therapeutic efficacy in murine systemic infection models with MSSA Smith and MRSA 10925, comparable to that of vancomycin, suggesting that the novel muraminomicin derivatives may be effective therapeutic agents against MRSA that warrant further investigation. A scheme for the formulation of the key ester intermediate, requiring no HPLC preparation, was also established.

Recent prescription status of oral analgesics in Japan in real-world clinical settings: retrospective study using a large-scale prescription database.

Background: Information on prescriptions of oral analgesics for the treatment of pain is beneficial. However, there have been few reports on the prescription status of oral analgesics from a nation-wide, large-scale prescription database in Japan. Research design and methods: The authors analyzed the prescription data of 2,042,302 patients prescribed oral analgesics in 2017. The numbers/proportions of patients prescribed oral analgesics, adherence with approved doses, co-prescription patterns, dose changes, drug adherence, and treatment-discontinuation rates were evaluated. Results: Loxoprofen was prescribed to 32.5% of the patients, followed by celecoxib, prescribed to 16.0% of patients. Acetaminophen and pregabalin were prescribed to 10.5% and 9.4% of patients, respectively. Many analgesics were prescribed at lower doses than the approved doses. The most frequently used concomitant medication was pregabalin. For duloxetine and pregabalin, high proportions of patients were prescribed these drugs for > 90 days. Conclusions: Loxoprofen was the most prescribed of the non-steroidal anti-inflammatory drugs in Japan. The information obtained provides an overview of prescribed oral analgesics in Japan and could be useful for potential research into prescribed oral analgesics in the future.

Total Synthesis of Pleofugin A, a Potent Inositol Phosphorylceramide Synthase Inhibitor.

X-ray analysis and total synthesis of 1 unambiguously confirmed pleofingin A's absolute configuration. The total synthesis was achieved by convergent assembly of three fragments (12, 14, and 18). This synthetic approach provides access to derivatives of 1 to search for antifungal agents that will be more effective in clinical use.