Average Daily Pain Intensity Score Research Articles

Rescue Analgesic Medication Use by Patients Treated with Triamcinolone Acetonide Extended-Release for Knee Osteoarthritis Pain: Pooled Analysis of Three Phase 2/3 Randomized Clinical Trials.

IntroductionIn clinical trials for knee osteoarthritis (OAK), rescue medication is commonly provided to manage uncontrolled index-knee pain. The impact of treatment on rescue medication utilization provides important information on the robustness of analgesic effect. In randomized controlled OAK trials (NCT01487161, NCT02116972, NCT02357459), intra-articular (IA) triamcinolone acetonide extended-release (TA-ER) demonstrated substantial, prolonged analgesia versus saline-placebo and TA crystalline solution (TAcs) as assessed by patient-reported pain scales. This pooled analysis assessed the impact of TA-ER on rescue medication use.MethodsPatients (N = 798) with OAK (American College of Rheumatology criteria; Kellgren–Lawrence grade 2/3) and baseline average daily pain intensity score ≥ 5 to ≤ 9 (0–10 numeric rating scale) received a single IA injection of TA-ER (N = 324), saline-placebo (N = 262), or TAcs (N = 212). Acetaminophen/paracetamol tablets were provided to treat uncontrolled pain (knee or otherwise). Rescue medication consumption was monitored through a daily diary; pill counts were confirmed at the clinical site. Differences in rescue medication use were measured by least-squares mean (LSM) differences, number of rescue medication tablets used per day, and in area under the effect (AUE) curves of rescue medication tablets used per week.ResultsThe overall number of rescue medication tablets used per day through week 24 was significantly less (p ≤ 0.05) for TA-ER versus saline-placebo (LSM difference, − 0.43) and TAcs (− 0.24). Rescue medication use was significantly (p ≤ 0.05) lower following TA-ER versus saline-placebo across weeks 1–12 (AUEweeks1–12; LSM difference, − 24.5) and weeks 1–24 (AUEweeks1–24; − 51.6) and versus TAcs across weeks 1–12 (AUEweeks1–12; − 21.1).ConclusionsIn patients with painful OAK, reduced rescue medication use may be a potential benefit of TA-ER and further supports its analgesic efficacy. Additional research is needed to assess whether TA-ER impacts the use of other common oral analgesics (nonsteroidal anti-inflammatory drugs, opioids) for patients with OAK.FundingFlexion Therapeutics, Inc., Burlington, MA, USA.Plain Language SummaryPlain language summary available for this article.

PMS41 - Cost Effectiveness Analysis of Intra-Articular Triamcinolone Acetonide Extended-Release Injectable Suspension (TA-ER) Versus Triamcinolone Acetonide Crystalline Suspension For Symptomatic Knee Osteoarthritis

To assess the cost-effectiveness of a single intra-articular (IA) injection of the recently-approved triamcinolone acetonide extended-release injectable suspension (TA-ER, formerly known as FX006) compared with conventional, commonly-used triamcinolone crystalline suspension (TAcs), in patients with symptomatic knee osteoarthritis (OA). We used a 3-state Markov model (TreeAge Software Inc., USA) to compare TA-ER (Flexion Therapeutics Inc., USA) with TAcs over 12 weeks. Analyses utilized patient-level data from three trials (NCT01487161, NCT02116972, NCT02357459). Participants with Kellgren-Lawrence Grade 2-3 knee OA and baseline Average Daily Pain-intensity scores of ≥5 to ≤9 were randomized to receive TA-ER 32 mg or TAcs 40 mg. Health Utilities Index Mark 3 (HUI-3) scores and Outcome Measures in Rheumatology (OMERACT)-OA Research Society International (OARSI)-defined “Strict” responder rates from previous pooled analyses were used to define utility scores and transition probabilities within the Markov model, respectively. Utility gained throughout the study was defined for responders versus non-responders and measured by area under the utility curve, expressed as quality-adjusted life years (QALYs). Costs included drug cost, physician assessment and injection fees, and conventional care. One-way sensitivity analysis used ±15% for continued response rates and QALYs gained per responder; all others were varied ±20%. Probabilistic sensitivity analyses and Monte Carlo simulations were also performed. The average utility gain for patients treated with TA-ER was 0.0281 QALYs over 12 weeks; cost/QALY was $4,570 and $1,515 for TA-ER and TAcs, respectively. The incremental cost-effectiveness ratio (ICER) of TA-ER was $19,883/QALY gained, sensitive to QALYs gained per responder and response rates in either TA-ER or TAcs groups. In Monte Carlo simulations, when willingness-to-pay threshold was set at $50,000/QALY, TA-ER was a cost-effective strategy in 63% of simulations. Compared with TAcs over a 3-month period, the $19,883/QALY ICER of TA-ER remained within the $50,000/QALY willingness-to-pay threshold to adopt a new treatment.

Fulranumab in patients with interstitial cystitis/bladder pain syndrome: observations from a randomized, double-blind, placebo-controlled study

BackgroundThis study was designed to evaluate the efficacy and safety of fulranumab, a fully human monoclonal antibody directed against nerve growth factor (NGF), for pain relief in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).MethodsIn this multicenter, double-blind study, adults with IC/BPS (i.e., interstitial cystitis symptom index [ICSI] total score ≥8) accompanied by chronic, moderate-to-severe pain were randomized to fulranumab 9 mg or matching placebo, administered subcutaneously at weeks 1, 5, and 9. The primary efficacy endpoint was change from baseline to study endpoint (week 12 or at withdrawal) in average daily pain intensity score. Key secondary endpoints included change from baseline to study endpoint in worst pain intensity score, ICSI total score, Pelvic Pain and Urgency/Frequency total score, Patient Perception of Bladder Condition score, and global response assessment.ResultsThis study was terminated prematurely based on concern that this class may be associated with rapidly progressing osteoarthritis or osteonecrosis. Thirty-one patients (of the targeted 70 patients) were randomized, 17 to placebo and 14 to fulranumab, with 15 and 10 patients, respectively, receiving all 3 doses of double-blind treatment. In ANOVA analyses, there was no statistically significant difference between treatment groups for the primary endpoint (LS mean difference [95% CI] vs. placebo, −0.2 [−1.52, 1.10]) or any of the secondary endpoints. Fulranumab was well tolerated, with no patient discontinuing due to an adverse event or experiencing a joint-related serious adverse event over a 26-week follow-up period. No events related to the neurologic or motor systems were reported.ConclusionsEfficacy was not demonstrated in the present study with the single dose tested and a limited sample size, leading to lack of statistical power. These findings do not exclude the possibility that fulranumab would provide clinical benefit in a larger study and/or specific populations (phenotypes) in this difficult to treat pain condition.Trial registrationNCT01060254, registered January 29, 2010.

Gastroretentive Gabapentin (G-GR) Formulation Reduces Intensity of Pain Associated With Postherpetic Neuralgia (PHN)

To evaluate the safety and efficacy of a once-daily gastroretentive formulation of gabapentin (G-GR; 1800 mg). This was an 11-week, double-blind, randomized, placebo-controlled Phase 3 clinical trial in patients with postherpetic neuralgia. Patients underwent a 2-week dose titration, 8 weeks of stable dosing, and 1 week of dose tapering. The primary endpoint was the change in average daily pain intensity score from Baseline to Week 10 using Baseline Observation Carried Forward (BOCF) imputation. Four-hundred and fifty-two patients (mean age 65.6 y, BMI 29 Kg/m) were randomized. Baseline average daily pain intensity score during the week prior to randomization was 6.6 and 6.5 for the G-GR and placebo treatment groups, respectively. Three hundred and seventy-seven patients completed the study (84% G-GR, 83% placebo). G-GR significantly reduced BOCF change in average daily pain intensity compared with placebo (-2.1 vs. -1.6; G-GR vs. placebo, P=0.013). Compared with placebo, more G-GR-treated patients reported "much" or "very much" improvement (patient global impression of change, 43% vs. 34%; P<0.0434), and G-GR reduced sleep interference (-2.3 vs. -1.59; P<0.0001), although neither endpoint was considered statistically significant based on a stringent hierarchical statistical paradigm. Other secondary endpoints showed similar trends. The most common adverse events were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%). Once-daily G-GR 1800 mg was effective and well tolerated for the relief of pain in patients with postherpetic neuralgia.

Gabapentin for once-daily treatment of post-herpetic neuralgia: a review

Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α2-δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%), dizziness (23.9%), and ataxia (7.1%). Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on the patient global impression of change. An analysis comparing the efficacy and safety profiles in the aging population (≥65 years) with those younger than 65 years showed that Gralise is effective and well tolerated in both age groups.

Efficacy and Safety of Etodolac-Paracetamol Fixed Dose Combination in Patients With Knee Osteoarthritis Flare-up: A Randomized, Double-blind Comparative Evaluation

To evaluate the efficacy and safety of etodolac-paracetamol combination in comparison with etodolac alone in patients with knee osteoarthritis (OA) flare-up. In this double-blind, double-dummy, randomized, comparative, multicentric, parallel group study, 220 patients of either sex in the age range of 40 to 70 years with an OA flare-up were randomized either to etodolac (300 mg)-paracetamol (500 mg) combination or etodolac (300 mg) alone twice a day for 10 days. Efficacy outcomes were an average daily pain intensity score on 11-point visual analog scale, Western Ontario and McMaster score (WOMAC), and Lequesne Severity Index; total pain relief score at 30 minutes, 1, 2, and 4 hours after first-dose administration; OA flare-up symptoms resolution; patient's and investigator's overall assessment of study treatments. Etodolac-paracetamol was significantly superior to etodolac alone in reducing pain intensity (P<0.001), achieving pain relief (P<0.05) during the first 4 hours after the study dose administration, and resolution of the clinical signs and symptoms of OA flare-up such as morning stiffness, swelling/inflammation, and erythema. The combination showed significantly greater improvement in WOMAC scores and Lequesne Severity Index (P<0.001) than in etodolac monotherapy. Peak pain intensity difference over a period of 10 days was also significantly (P<0.001) higher in combination-treated patients compared with monotherapy-treated patients. The combination had significantly better patient's and investigator's global efficacy assessment (P=0.001). Both treatments were well tolerated and safe in patients with OA flare-up. For the treatment of painful OA flare-ups, the etodolac-paracetamol combination can offer improved clinical outcomes by targeting multiple pain pathways. The results of the current study show that etodolac-paracetamol is more effective in the treatment of OA flare-up than etodolac alone.

A Randomized, Double-Blind, Placebo-Controlled Trial of a Selective COX-2 Inhibitor, GW406381, in Patients With Postherpetic Neuralgia

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy and safety of GW406381, an investigational selective cyclooxygenase (COX)-2 inhibitor with both peripheral and central actions, in 209 patients with postherpetic neuralgia (PHN). Patients were randomly assigned to GW406381 25 mg or 50 mg or placebo treatments for 3 weeks. The primary efficacy outcome measure was the change in average daily pain intensity score from baseline to the last week of treatment. Both doses of GW406381 produced greater reduction in pain score than placebo, but the treatment difference did not reach statistical significance. It was possible that the 3-week duration was too short, as there was a tendency for increasing separation from placebo over time that did not appear to reach maximum effect by the end of the study for either GW406381 treatment group. Overall, GW406381 was well tolerated in this elderly population. To our knowledge, this is the first report of a randomized, controlled clinical trial of a selective or nonselective COX inhibitor in neuropathic pain. The results of this study were inconclusive regarding the clinical relevance of the role of COX-2 in modulation of the symptoms of PHN.

PR_107: A Randomized, Open-Label Study Comparing the Efficacy and Safety of a 5% Lidocaine Patch With 200mg/d of Celecoxib in Patients With Chronic Axial Low Back Pain

Objective: To compare the efficacy and safety of a 5% lidocaine patch with that of 200mg/d celecoxib in treating chronic axial low back pain (LBP). Design: Multicenter, open-label, parallel-group randomized, active-controlled, pilot study. Setting: Office-based practice. Participants: Adult patients (n=122) with LBP with or without radiation who had average daily pain intensity scores of ≥5 for at least 3 of the 5 days prior to baseline visit (measured by question 5 of the Brief Pain Index [BPI]).

Transdermal fentanyl in the management of children with chronic severe pain

The current study was conducted to assess the safety and tolerability of a transdermal fentanyl delivery system for the relief of chronic pain in a pediatric population, and also to validate titration recommendations and conversion to transdermal fentanyl from oral opioid therapy. This 15-day (with 3-month extension), single-arm, open-label trial was conducted at 66 sites in 10 countries. A total of 199 pediatric patients (ages 2-16 years) with both malignant and nonmalignant conditions who were receiving oral or parenteral opioids for moderate to severe chronic pain were enrolled. Transdermal fentanyl doses were titrated upward according to the rescue medication consumed during the previous application period. Degree of pain was assessed by patients and parents/guardians using visual and numeric scales. Level of play and quality of life were assessed using the Play Performance Scale (PPS) and the Child Health Questionnaire (CHQ). Adverse events were monitored on Days 1-15. Hypoventilation and sedation were monitored every 4 hours during the first 72 hours of the study. A total of 173 patients completed the primary treatment period and 130 entered the extension phase. The average daily pain intensity scores were reported to have decreased by Day 16 and improvements in the mean PPS scores were observed to the end of the extension period. The CHQ scores demonstrated improvements in 11 of 12 domains after Month 1 of the extension period. Transdermal fentanyl was found to be a safe and well tolerated alternative to oral opioid treatment for children ages 2-16 years who were previously exposed to opioid therapy.

A randomized, open-label study comparing the efficacy and safety of lidocaine patch 5% with celecoxib 200 mg in patients with pain from osteoarthritis of the knee

Animal models of osteoarthritis (OA) pain suggest that upregulation of sodium (Na) channel expression in primary afferent neurons induced by joint inflammation may result in OA pain and hyperalgesia. Because the lidocaine patch 5% acts by blocking abnormally functioning Na channels and decreasing ectopic nociceptive pain signal transmission, it may produce an analgesic response when applied to arthritic joints. Therefore, the lidocaine patch 5% may provide a useful non-systemic treatment option for OA. The objective of this randomized, open-label, activecontrol, parallel-group study was to compare the efficacy of the lidocaine patch 5% with that of celecoxib 200 mg in treating pain from OA of the knee. After a 14-day washout period during which all analgesic medications were discontinued, 200 patients with unilateral or bilateral OA of the knee with an average daily pain intensity score 5 on a scale of 0 to 10 for 3 of 5 consecutive days and an OA severity score of 7 on a scale of 0 to 24 prior to the baseline visit were randomized to 12 weeks’ treatment with the lidocaine patch 5% (n 100) or celecoxib 200 mg (n 100). Patients receiving the lidocaine patch 5% applied 1 1/3 patches on each affected knee every 24 hours. Efficacy measures included the Western Ontario and McMaster Universities OA Index, the Brief Pain Index, the Pain Quality Assessment Scale, and global assessments of change in OA pain and treatment satisfaction. Quality-of-life evaluations included the Beck Depression Inventory and sleep quality. Assessments of safety included adverse events, skin assessments (lidocaine group only), laboratory tests, vital signs, and physical examination. Data from the study will be presented at the meeting. This study is funded by Endo Pharmaceuticals, Inc.

Poster 95: A 5% lidocaine patch significantly improves pain intensity and pain relief in the treatment of low back pain

Objective: To assess the effectiveness of a 5% lidocaine patch (Lidoderm), a targeted peripheral analgesic, in acute and chronic low back pain (CLBP) after 2 weeks of daily treatment. Design: Open-label, nonrandomized, 2-week, multicenter trial. Setting: Clinic. Participants: Men and women aged ≥18 years with nonradicular acute and subacute (<3mo: group 1; n=21), short-term chronic (3–12mo: group 2; n=33), and long-term (>12mo: group 3; n=77) CLBP, an average daily pain intensity score >4 (scale range, 0–10) within 24 hours prior to screening, and normal neurologic examination and clinical laboratory tests. Intervention: Patients applied up to 4 lidocaine patches every 24 hours to the area of maximal peripheral pain for 2 weeks and were maintained on their current analgesic regimen without dosage adjustment. Main Outcome Measures: Brief Pain Inventory (BPI) and Beck Depression Inventory (BDI). Results: In groups 1 and 3, patients treated with the lidocaine patch experienced statistically significant improvements in pain intensity ( P<.001) and pain relief ( P<.0001) as measured by the BPI. In group 2, significant improvements were observed for worst pain ( P<.001), and average pain and pain right now ( P<.05). Groups 1, 2, and 3 experienced statistically significant reductions in the BPI composite score for pain interference with quality of life scores ( P<.0001) and BDI score ( P<.01, P<.0001, P<.0001, respectively). There were no serious systemic adverse events or drug-drug interactions related to the lidocaine patch. Conclusions: Findings of this 2-week, open-label study suggest that the 5% lidocaine patch was well tolerated and effective in lowering pain intensity, improving pain relief, and lowering pain interference in patients with LBP. Further controlled trials are warranted.