- Email: [email protected]
NSAIDs and acetaminophen
Abstracts (817) Botulinum toxin type A for failed back syndrome K. Edwards, M. Dreyer; Neurological Research Center, Bennington, VT Chronic low back pain (LBP) is usually a debilitating syndrome with musculoskeletal and neuropathic pain features. Prior studies have shown that botulinum toxin type A (BTX-A) is efficacious for LBP. We retrospectively reviewed charts of 17 consecutive patients who were referred for chronic LBP, who had prior lumbar surgery and who were treated with BTX-A injections given bilaterally in the lumbar paravertebral muscles. Pain ratings included the Visual Analogue Scale (VAS), the Short Form McGill Pain Questionnaire (SFMPQ)and Present Pain Intensity (PPI) before injection and at a mean of 6 weeks post-injection. Adverse events were assessed. Nine patients received 100 to 200 units of BTX-A (only one patient received 100) and 8 patients received between 300 and 400 units BTX-A (only one patient received 400). The mean dose of BTX-A was 250 units. Most patients received BTX-A via a 26-gauge, 50 mm or 37 mm EMG guided injection to ensure intramuscular injection in these post-operative patients. Results of BTX-A treatment were pretreatment VAS mean of 79 and post-treatment mean of 62 (p⫽0.008). Pre-treatment SFMPQ mean was 24; post-treatment SFMPQ mean was 16 (p⫽0.007). Pre-treatment PPI mean was 3.4; post-treatment PPI mean was 2.5 (p⫽0.01). Side effects were limited to transient injection site discomfort. No patients developed weakness. A sub-analysis of patients receiving 300 units BTX-A compared to patients receiving 200 units BTX showed greater efficacy at 300 units. BTX-A appears to be effective in a high percentage of patients with significant, long-term LBP who have failed surgery and multiple other modalities of treatment. No significant side effects occured in any of our patients.
63
D13 - NSAIDs and Acetaminophen (819) Comparison of acetaminophen and naproxen for the management of mild-to-moderate osteoarthritis pain of the hip or knee J. Zinsenheim, G. Benson, J. Schweinle, A. Temple, S. Silber, D. Bowen; McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA This study was designed to assess the safety of acetaminophen (APAP) and naproxen (NAP) for the long-term treatment of osteoarthritis (OA) of the hip or knee. Measures of changes in pain, joint stiffness, and physical function were obtained, and results of these measures from the first 6 study months are presented in this preliminary report. This was a multicenter, randomized, double-blind, parallel-group, comparative study of subjects 40 to 75 years of age with mild-to-moderate OA pain of the hip or knee. After a pain medication washout period and subsequent flare, subjects received 4000 mg/d APAP (n⫽276) or 750 mg/d NAP (n⫽275). The primary efficacy variable was change from baseline in the WOMAC pain subscale at endpoint (last measure carried forward) for all subjects who took GT/ET one dose of study medication and had GT/ET one post- baseline evaluation. There were no significant differences in demographic characteristics between APAP and NAP subjects. At endpoint, mean changes from baseline for the APAP and NAP groups were respectively: –21.6 (1.82)* and –21.9 (1.74) (P⫽0.8847) for the WOMAC subscale for pain; –20.6 (1.96) and –21.0 (1.86) (P⫽0.8529) for stiffness; and –18.9 (1.83) and –20.1 (1.76) (P⫽0.5842) for physical function. Analyses of means at 1, 3, and 6 months also showed no differences between APAP and NAP. Safety assessments were performed for subjects who took GT/ET one dose of active medication. The only serious drug-related adverse event was a severe gastrointestinal hemorrhage with severe anemia in a NAP-treated subject. Additional safety analyses are currently underway. APAP and NAP produced similar reductions in pain, stiffness, and physical function associated with mild-to-moderate OA of the hip or knee. Thus, APAP and NAP appear to be of equal benefit in reducing these signs and symptoms of OA. *Least square means (standard error).
(818) Zonisamide as adjunct medication in the symptomatic treatment of idiopathic painful neuropathy
(820) Efficacy of Rofecoxib 50 mg in patients with moderate or severe pain: A meta-analysis of 13 clinical trials
Z. Sahenk, B. McCracken, J. Kissel; Ohio State University, Department of Neurology, Columbus, OH Idiopathic painful neuropathy (IPN) treated with monotherapy generally results in 30-40% reduction in pain. While using a combination of drugs with different mechanisms of action is a logical strategy, supporting data are lacking. The aim was to evaluate efficacy and tolerability of zonisamide as add-on medication in patients with IPN who failed gabapentin monotherapy. The study was conducted over 13 weeks as an open-label add-on trial with a slow titration schedule, and included 4 clinic and 6 telephone visits. Subjects completed the Beck Depression Inventory and McGill Short Form Pain Questionnaire (MSFPQ) at each clinic visit with a 10-cm visual analogue scale (VAS), rating pain intensity. Eleven pain items in MSFPQ referring to physical or sensory modifiers were analyzed. Total score of 11 pain items at baseline and final visit were compared. Scores for individual pain items, the mean VAS from the last 3 visit scores were compared to baseline using the paired t test. Twenty-one patients with IPN were screened; 19 were enrolled. Seven completed the study; 2 dropped due to allergic reaction, 3 due to drowsiness, 6 due to lack of efficacy and 1 was lost to follow-up. Those patients who completed the study remained on a steady dose of gabapentin (1200-3200 mg/day). Zonisamide significantly improved the total score of 11 pain items at final visit and at mean VAS value. Significant improvements in hot-burning (p⬍0.012), cramping (p⬍ 0.016) and shooting (p⬍0.006) pain occurred when the mean VAS values were compared to baseline. Only hot-burning pain was significantly reduced at final visit (p⬍0.004). Other pain modalities did not show statistical improvement. VAS for pain was improved from the baseline value of 70.62⫹10.62 to the mean VAS value of 50.51⫹10.37 (n⫽7, p⬍0.028). Zonisamide as adjunct therapy improves many neuropathic pain components and VAS in some patients with IPN.
D. Mehlisch, P. Desjardins, D. Krupa, A. Polis, R. Petruschke, G. Geba, D. Chang Merck & Co., Inc., West Point, PA This meta-analysis was performed to determine if rofecoxib provided differential analgesic efficacy among patients with moderate (MOD) or severe (SEV) pain in a validated acute pain model. Meta-analysis was performed on individual patient data from 13 similarly designed, randomized, double-blind, placebo-controlled studies involving patients experiencing MOD or SEV pain after surgical extraction of at least 2 third molars. Patients were stratified by baseline pain of MOD or SEV. 1329 patients treated with rofecoxib 50 mg (MOD:N⫽894; SEV:N⫽435) and 570 patients treated with placebo (MOD:N⫽393; SEV:N⫽177) were analyzed. Overall analgesic effect was measured by total pain relief over 8 hours (TOPAR8). Patient global assessment at 24 hours was analyzed to determine responders (excellent, very good, good) from non-responders (poor, fair). Time to onset of analgesia based on time to confirmed perceptible pain relief was also measured. TOPAR8 scores were similar between MOD and SEV groups with rofecoxib 50 mg (17.5 and 17.4, respectively). Rofecoxib provided greater pain relief on TOPAR8 than placebo in both MOD and SEV groups (P⬍0.001) of similar magnitude of difference from placebo (12.9 and 13.2, respectively). For patient global assessment, a similar proportion of MOD and SEV patients rated their response to rofecoxib 50 mg as good, very good, or excellent (73.2% and 72.6%, respectively). Time to confirmed perceptible pain relief with rofecoxib was similar for MOD and SEV patients (33 minutes and 36 minutes, respectively); the same percentage of patients in each group achieved confirmed perceptible pain relief (76.8%). This meta-analysis of over 1300 patients with acute pain demonstrates that differences in baseline pain severity do not affect analgesic response to rofecoxib 50 mg. Rofecoxib 50 mg may be used for management of both moderate and severe pain with similar rapid onset of action and analgesic efficacy.
63
D13 - NSAIDs and Acetaminophen (819) Comparison of acetaminophen and naproxen for the management of mild-to-moderate osteoarthritis pain of the hip or knee J. Zinsenheim, G. Benson, J. Schweinle, A. Temple, S. Silber, D. Bowen; McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA This study was designed to assess the safety of acetaminophen (APAP) and naproxen (NAP) for the long-term treatment of osteoarthritis (OA) of the hip or knee. Measures of changes in pain, joint stiffness, and physical function were obtained, and results of these measures from the first 6 study months are presented in this preliminary report. This was a multicenter, randomized, double-blind, parallel-group, comparative study of subjects 40 to 75 years of age with mild-to-moderate OA pain of the hip or knee. After a pain medication washout period and subsequent flare, subjects received 4000 mg/d APAP (n⫽276) or 750 mg/d NAP (n⫽275). The primary efficacy variable was change from baseline in the WOMAC pain subscale at endpoint (last measure carried forward) for all subjects who took GT/ET one dose of study medication and had GT/ET one post- baseline evaluation. There were no significant differences in demographic characteristics between APAP and NAP subjects. At endpoint, mean changes from baseline for the APAP and NAP groups were respectively: –21.6 (1.82)* and –21.9 (1.74) (P⫽0.8847) for the WOMAC subscale for pain; –20.6 (1.96) and –21.0 (1.86) (P⫽0.8529) for stiffness; and –18.9 (1.83) and –20.1 (1.76) (P⫽0.5842) for physical function. Analyses of means at 1, 3, and 6 months also showed no differences between APAP and NAP. Safety assessments were performed for subjects who took GT/ET one dose of active medication. The only serious drug-related adverse event was a severe gastrointestinal hemorrhage with severe anemia in a NAP-treated subject. Additional safety analyses are currently underway. APAP and NAP produced similar reductions in pain, stiffness, and physical function associated with mild-to-moderate OA of the hip or knee. Thus, APAP and NAP appear to be of equal benefit in reducing these signs and symptoms of OA. *Least square means (standard error).
(818) Zonisamide as adjunct medication in the symptomatic treatment of idiopathic painful neuropathy
(820) Efficacy of Rofecoxib 50 mg in patients with moderate or severe pain: A meta-analysis of 13 clinical trials
Z. Sahenk, B. McCracken, J. Kissel; Ohio State University, Department of Neurology, Columbus, OH Idiopathic painful neuropathy (IPN) treated with monotherapy generally results in 30-40% reduction in pain. While using a combination of drugs with different mechanisms of action is a logical strategy, supporting data are lacking. The aim was to evaluate efficacy and tolerability of zonisamide as add-on medication in patients with IPN who failed gabapentin monotherapy. The study was conducted over 13 weeks as an open-label add-on trial with a slow titration schedule, and included 4 clinic and 6 telephone visits. Subjects completed the Beck Depression Inventory and McGill Short Form Pain Questionnaire (MSFPQ) at each clinic visit with a 10-cm visual analogue scale (VAS), rating pain intensity. Eleven pain items in MSFPQ referring to physical or sensory modifiers were analyzed. Total score of 11 pain items at baseline and final visit were compared. Scores for individual pain items, the mean VAS from the last 3 visit scores were compared to baseline using the paired t test. Twenty-one patients with IPN were screened; 19 were enrolled. Seven completed the study; 2 dropped due to allergic reaction, 3 due to drowsiness, 6 due to lack of efficacy and 1 was lost to follow-up. Those patients who completed the study remained on a steady dose of gabapentin (1200-3200 mg/day). Zonisamide significantly improved the total score of 11 pain items at final visit and at mean VAS value. Significant improvements in hot-burning (p⬍0.012), cramping (p⬍ 0.016) and shooting (p⬍0.006) pain occurred when the mean VAS values were compared to baseline. Only hot-burning pain was significantly reduced at final visit (p⬍0.004). Other pain modalities did not show statistical improvement. VAS for pain was improved from the baseline value of 70.62⫹10.62 to the mean VAS value of 50.51⫹10.37 (n⫽7, p⬍0.028). Zonisamide as adjunct therapy improves many neuropathic pain components and VAS in some patients with IPN.
D. Mehlisch, P. Desjardins, D. Krupa, A. Polis, R. Petruschke, G. Geba, D. Chang Merck & Co., Inc., West Point, PA This meta-analysis was performed to determine if rofecoxib provided differential analgesic efficacy among patients with moderate (MOD) or severe (SEV) pain in a validated acute pain model. Meta-analysis was performed on individual patient data from 13 similarly designed, randomized, double-blind, placebo-controlled studies involving patients experiencing MOD or SEV pain after surgical extraction of at least 2 third molars. Patients were stratified by baseline pain of MOD or SEV. 1329 patients treated with rofecoxib 50 mg (MOD:N⫽894; SEV:N⫽435) and 570 patients treated with placebo (MOD:N⫽393; SEV:N⫽177) were analyzed. Overall analgesic effect was measured by total pain relief over 8 hours (TOPAR8). Patient global assessment at 24 hours was analyzed to determine responders (excellent, very good, good) from non-responders (poor, fair). Time to onset of analgesia based on time to confirmed perceptible pain relief was also measured. TOPAR8 scores were similar between MOD and SEV groups with rofecoxib 50 mg (17.5 and 17.4, respectively). Rofecoxib provided greater pain relief on TOPAR8 than placebo in both MOD and SEV groups (P⬍0.001) of similar magnitude of difference from placebo (12.9 and 13.2, respectively). For patient global assessment, a similar proportion of MOD and SEV patients rated their response to rofecoxib 50 mg as good, very good, or excellent (73.2% and 72.6%, respectively). Time to confirmed perceptible pain relief with rofecoxib was similar for MOD and SEV patients (33 minutes and 36 minutes, respectively); the same percentage of patients in each group achieved confirmed perceptible pain relief (76.8%). This meta-analysis of over 1300 patients with acute pain demonstrates that differences in baseline pain severity do not affect analgesic response to rofecoxib 50 mg. Rofecoxib 50 mg may be used for management of both moderate and severe pain with similar rapid onset of action and analgesic efficacy.