Pain severity and healthcare resource utilization in patients with osteoarthritis in the United States.

OBJECTIVE: To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity. METHODS: Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0-3), moderate (4-6), and severe (7-10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed. RESULTS: Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6; p < 0.0001). Pain severity was associated with an increased number of physician-reported and patient-reported overall healthcare provider visits (HCPs; both p < 0.001). As pain increased, patients reported an increased need for mobility aids, accessibility modifications to homes, and help with daily activities due to functional disability. The number of imaging tests used to diagnose OA was similar across pain severity but varied when used for monitoring (X-rays: p < 0.0001; computerized tomography scans: p < 0.0447). Hospitalization rates for OA were low but were significantly associated with pain severity (mild: 4.9%; severe: 11.5%). Emergency department visits were infrequent but increasing pain severity was associated with more prior and planned surgeries. CONCLUSION: Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU.

A Randomized, Crossover, Pharmacokinetic and Adhesion Performance Study of a Lidocaine Topical System 1.8% During Physical Activity and Heat Treatment in Healthy Subjects.

PURPOSE: This study compares the pharmacokinetic (PK) profile, adhesion, and safety of lidocaine topical system 1.8%, a novel lidocaine topical system approved to treat postherpetic neuralgia, under conditions of heat and exercise vs normal conditions. MATERIALS AND METHODS: This open-label, 3-period, 3-treatment crossover study randomized 12 healthy adults to receive three lidocaine topical systems 1.8% during each of three treatment periods, with 7-day washouts between treatments. The product was applied to the mid-lower back and was removed after 12 hours. During Treatment A, subjects exercised on a bicycle for 30 minutes at 0, 2.5, 5.5, and 8.5 hours. During Treatment B, heat (temperature set at 36.7-40.3°C) was applied at 0 and 8.5 hours. Treatment C was normal conditions. The PK profile of each subject under exercise and heat conditions was compared to normal conditions. Skin irritation, adhesion, and adverse events were assessed. RESULTS: Twelve subjects completed the study. Exposure to external heat resulted in increased peak plasma concentration of lidocaine with a mean Cmax of 160.3±100.1 ng/mL vs 97.6±36.9 ng/mL under normal conditions, with no effect on the extent of exposure (AUC). Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in absorption were observed under exercise conditions with a mean Cmax of 90.5±25.4 ng/mL and no effect on the extent (AUC) of lidocaine exposure was observed relative to normal conditions. No systems detached during the study. Adverse events were mild, with none leading to discontinuation. CONCLUSION: Transient heat exposure resulted in increased lidocaine plasma concentrations compared to normal conditions, whereas exercise had no effect. The effects of heat appear to be immediate, reversible, and below systemic therapeutic threshold in antiarrhythmic treatment (1000-1500 ng/mL), and well below the safe systemic threshold of 5000 ng/mL. Lidocaine topical system 1.8% remained adhered to the skin and was well tolerated under all conditions. ClinicalTrials.gov: NCT04150536.

A Randomized, Open-Label, Bioequivalence Study of Lidocaine Topical System 1.8% and Lidocaine Patch 5% in Healthy Subjects.

PURPOSE: This study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies. PATIENTS AND METHODS: Two Phase 1, single-center, open-label, randomized PK studies were performed in healthy adults. In Study 1, 56 subjects received a single intravenous bolus of 0.7 mg/kg of lidocaine as a lead-in to allow for the accurate determination of apparent dose of both products. After a 7-day washout period, subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours followed by another 7-day washout period, after which subjects crossed over to receive the other treatment for 12 hours. In Study 2, 54 subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours. After a 7-day washout period, subjects crossed over to receive the other treatment. Adhesion and skin irritation assessments were performed after application of the products in Study 2. In both studies, serial blood samples were collected to measure the plasma concentration of lidocaine after product application. Safety assessments and adverse events were monitored in both studies. RESULTS: The comparative PK analysis demonstrated that the two products, despite their difference in drug load and strength, are bioequivalent. Both products were well tolerated. In Study 2, dermal response scores (skin tolerability after removal) were similar between lidocaine topical system 1.8% and lidocaine patch 5%, with a mean irritation score per patch <1 (barely perceptible erythema), which is not considered to be clinically significant. CONCLUSION: Bioequivalence was demonstrated between lidocaine topical system 1.8% and lidocaine patch 5%. A comparison of the single-time adhesion scores at 12 hours in Study 2 favored lidocaine topical system 1.8% over lidocaine patch 5%. Both products were well tolerated as a single application in healthy adult human subjects. CLINICALTRIALSGOV: NCT04144192, NCT04149938.

Utility of lidocaine as a topical analgesic and improvements in patch delivery systems.

Interest in and use of topical analgesics has been increasing, presumably due to their potential utility for relief of acute and chronic pain. Topically applied agents with analgesic properties can target peripheral nociceptive pathways while minimizing absorption into the plasma that leads to potential systemic adverse effects.Clinical trials have found 5% lidocaine patches to be effective and well tolerated for the treatment of post-herpetic neuralgia (PHN) with a minimal risk of toxicity or drug-drug interactions. With this patch formulation, the penetration of lidocaine into the skin produces an analgesic effect without producing a complete sensory block. Use of topical lidocaine is supported by clinical practice guidelines, including first-line treatment by the American Academy of Neurology (guidelines retired 2018), the European Federation of Neurological Societies and second-line by the Canadian Pain Society.FDA approved 5% lidocaine patches in 1999, and a 1.8% topical lidocaine system in 2018 - both indicated for the treatment of pain secondary to PHN. The 1.8% system offers a more efficient delivery of lidocaine that is bioequivalent to 5% lidocaine patches, but with a 19-fold decrease in drug load (i.e., 36 mg versus 700 mg) as well as superior adhesion that allows the patch to maintain contact with the skin during the 12-h administration period.Although topical lidocaine formulations have advanced over time and play an important role in the treatment of PHN, a variety of other conditions that respond to topical lidocaine have been reported in the literature including PHN, lower back pain, carpal tunnel syndrome, diabetic peripheral neuropathy, and osteoarthritis joint pain. Other neuropathic or nociceptive pain syndromes may respond to topical lidocaine in select cases and warrant further study. Clinicians should consider local anesthetics and other topical agents as part of their multimodal treatments of acute and chronic pain.