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S24 (692) Differential changes in mu-opioid receptor (MOR) availability following acupuncture and sham acupuncture therapy in fibromyalgia (FM) patients R Harris, D Scott, R Gracely, D Clauw, J Zubieta; University of Michigan, Ann Arbor, MI Multiple lines of evidence implicate MORs in analgesia following placebo and acupuncture treatments. No study has examined the differential effects of these two interventions on binding of central MORs in chronic pain patients. We investigated the relationship between changes in MOR availability following acupuncture and sham acupuncture and subsequent changes in clinical pain. 18 female FM patients (ages 18-75) were randomized to receive either one acupuncture (n⫽9) or one sham acupuncture (n⫽9) treatment. Acupuncture treatment involved insertion of 9 sterile single-use acupuncture needles into the body whereas sham treatment did not involve skin penetration. Prior to and during treatment, all subjects underwent a 90 minute 11C-carfentanil positron emission tomography (PET) scan with needle insertion occurring at 40 minutes. Clinical pain was assessed pre- and post-treatment with the Gracely Box Scale (GBS). PET images were processed with Logan plot analysis resulting in maps of whole-brain MOR binding potential (BP). Correlations between changes in clinical pain and MOR BP were performed using SPSS v14.0. The acupuncture group displayed slightly greater reductions in clinical pain, but this was not statistically different between groups (mean difference pre-post⫹SD: acu⫽1.4⫹4.7; sham⫽0.3⫹2.8; p⫽0.54). Within the right inferior insula and right nucleus accumbens, MOR BP increased following acupuncture but not sham acupuncture (BP mean difference pre-post⫹SD: insula acu⫽0.36⫹0.30, sham⫽-0.07⫹0.25; p⫽0.04; accumbens acu⫽-0.45⫹0.52, sham⫽-0.05⫹16; p⫽0.04). Changes in clinical pain were positively correlated with changes MOR BP in the insula (r⫽0.70; p⫽0.04) and accumbens (r⫽0.76; p⫽0.02) in the acupuncture but not the sham group (insula r⫽-0.47; p⫽0.24; accumbens r⫽0.06; p⫽0.89). There are differential effects of acupuncture and sham acupuncture on MOR BP in chronic pain patients, and these effects are associated with acupuncture efficacy.
(693) Withdrawn
Abstracts (694) Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM) trial: A 6-month, double-blind, placebo-controlled trial of treatment with pregabalin L Crofford, S Simpson, J Young, G Haig, J Barrett; Pfizer Global Pharmaceuticals, New York, NY We report on a trial (FREEDOM) designed to evaluate pregabalin for durability of effect in reducing pain associated with FMS. This placebocontrolled, double-blind study consisted of a 1-week screening phase; a 6-week open-label phase (individualized dosage optimization to 300, 450, or 600 mg/d); and a 26-week double-blind phase. Patients who had ⱖ50% reduction in mean pain VAS score from open-label baseline and scored “much improved” or “very much improved” on the PGIC at 2 of the final 3 visits in open-label were eligible for randomization to placebo or their optimal dosage of pregabalin. The primary endpoint of the double-blind phase was time to loss of therapeutic response (LTR), defined as ⬍30% reduction in pain VAS score (from open-label baseline) during 2 consecutive visits or subjective worsening of FMS symptoms. 6 sensitivity analyses--using alternative definitions of LTR based on different assumptions about censored patients--were performed. 1051 patients entered open-label: 93% were female, 88% were white; mean age⫽50 years, FMS median duration⫽7.8 years, baseline mean pain VAS score⫽78 mm. 663 patients completed open-label; 566 were randomized: 279 to pregabalin, 287 to placebo. Time to LTR was significantly longer for pregabalin vs placebo (P⬍.0001): 25% of placebo patients had LTR by Day 7, compared with Day 34 for pregabalin patients. Nearly twice as many placebo patients (174; 61%) had LTR by end of doubleblind vs pregabalin patients (90; 32%). All 6 sensitivity analyses confirmed the robustness of these findings: in each analysis, time to LTR was significantly longer for pregabalin vs placebo (P⬍.0001). Dizziness (36%) and somnolence (22%) were the most common treatment-associated AEs during open-label. In double-blind, the most common AEs exceeding placebo were sinusitis (5% vs 3%), arthralgia and anxiety (5% vs 2%). Pregabalin significantly delayed time to LTR, demonstrating durability of maintaining pain reduction in patients with FMS.
(695) A 14-week, randomized, double-blind, placebo-controlled, monotherapy trial of pregabalin (BID) in patients with fibromyalgia syndrome (FMS) L Arnold, I Russell, W Duan, E Diri, J Young, S Martin, U Sharma, G Haig, T Griesing; Pfizer Global R & D, Ann Arbor, MI This double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of pregabalin for management of FMS. Patients meeting ACR criteria and who had mean baseline pain score ⱖ4 (on an 11-point NRS) and pain VAS score ⱖ40 mm (0-100 –mm scale) entered a 1-week, single-blind, placebo–run-in period. Those who had ⱖ30% reduction in VAS score during placebo run-in were discontinued. Other qualified patients were randomized to pregabalin 300, 450, or 600 mg/d (BID) or placebo for 14 weeks of treatment (2-week dosage escalation and 12week fixed-dosage). Primary efficacy parameters were endpoint mean pain score (NRS from daily pain diary), PGIC, and Fibromyalgia Impact Questionnaire (FIQ). 745 patients were randomized: 95% were female, mean age⫽50 years, median FMS duration⫽8 years, baseline mean pain score⫽6.7. 486 (65%) completed the trial. Pregabalin significantly improved pain: differences from placebo in mean change from baseline to endpoint in mean pain score were, 300 mg/d, 0.71 (P⫽.0009); 450 mg/d, -0.98, and 600 mg/d, -1.00 (each P⬍.0001). Significantly greater proportions of patients responded (ⱖ30% improvement) to pregabalin than placebo: 300, 42% (P⫽.0172); 450, 50% (P⫽.0002); 600 mg/d, 48% (P⫽.0006); placebo, 30%. Significant changes in mean pain score were evident as early as Week 1 and were sustained to endpoint. On the PGIC, there was statistically significant improvement for all pregabalin groups compared with placebo, with 68% of 300-, 78% of 450-, and 66% of 600-mg/d patients reporting at least minimal improvement vs 48% of placebo. On the FIQ, patients in the 450- and 600-mg/d groups showed statistically significant improvement vs placebo (treatment differences: 450 mg/d, -5.24, P⫽.0041; 600 mg/d, -5.34, P⫽.0034). The most common AEs were dizziness (all pregabalin, 35.8%; placebo, 7.6%) and somnolence (18.0%; 3.8%). Pregabalin, at all dosages, demonstrated rapid and sustained pain relief and at 450 and 600 mg/d demonstrated effective management of FMS.
(693) Withdrawn
Abstracts (694) Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM) trial: A 6-month, double-blind, placebo-controlled trial of treatment with pregabalin L Crofford, S Simpson, J Young, G Haig, J Barrett; Pfizer Global Pharmaceuticals, New York, NY We report on a trial (FREEDOM) designed to evaluate pregabalin for durability of effect in reducing pain associated with FMS. This placebocontrolled, double-blind study consisted of a 1-week screening phase; a 6-week open-label phase (individualized dosage optimization to 300, 450, or 600 mg/d); and a 26-week double-blind phase. Patients who had ⱖ50% reduction in mean pain VAS score from open-label baseline and scored “much improved” or “very much improved” on the PGIC at 2 of the final 3 visits in open-label were eligible for randomization to placebo or their optimal dosage of pregabalin. The primary endpoint of the double-blind phase was time to loss of therapeutic response (LTR), defined as ⬍30% reduction in pain VAS score (from open-label baseline) during 2 consecutive visits or subjective worsening of FMS symptoms. 6 sensitivity analyses--using alternative definitions of LTR based on different assumptions about censored patients--were performed. 1051 patients entered open-label: 93% were female, 88% were white; mean age⫽50 years, FMS median duration⫽7.8 years, baseline mean pain VAS score⫽78 mm. 663 patients completed open-label; 566 were randomized: 279 to pregabalin, 287 to placebo. Time to LTR was significantly longer for pregabalin vs placebo (P⬍.0001): 25% of placebo patients had LTR by Day 7, compared with Day 34 for pregabalin patients. Nearly twice as many placebo patients (174; 61%) had LTR by end of doubleblind vs pregabalin patients (90; 32%). All 6 sensitivity analyses confirmed the robustness of these findings: in each analysis, time to LTR was significantly longer for pregabalin vs placebo (P⬍.0001). Dizziness (36%) and somnolence (22%) were the most common treatment-associated AEs during open-label. In double-blind, the most common AEs exceeding placebo were sinusitis (5% vs 3%), arthralgia and anxiety (5% vs 2%). Pregabalin significantly delayed time to LTR, demonstrating durability of maintaining pain reduction in patients with FMS.
(695) A 14-week, randomized, double-blind, placebo-controlled, monotherapy trial of pregabalin (BID) in patients with fibromyalgia syndrome (FMS) L Arnold, I Russell, W Duan, E Diri, J Young, S Martin, U Sharma, G Haig, T Griesing; Pfizer Global R & D, Ann Arbor, MI This double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of pregabalin for management of FMS. Patients meeting ACR criteria and who had mean baseline pain score ⱖ4 (on an 11-point NRS) and pain VAS score ⱖ40 mm (0-100 –mm scale) entered a 1-week, single-blind, placebo–run-in period. Those who had ⱖ30% reduction in VAS score during placebo run-in were discontinued. Other qualified patients were randomized to pregabalin 300, 450, or 600 mg/d (BID) or placebo for 14 weeks of treatment (2-week dosage escalation and 12week fixed-dosage). Primary efficacy parameters were endpoint mean pain score (NRS from daily pain diary), PGIC, and Fibromyalgia Impact Questionnaire (FIQ). 745 patients were randomized: 95% were female, mean age⫽50 years, median FMS duration⫽8 years, baseline mean pain score⫽6.7. 486 (65%) completed the trial. Pregabalin significantly improved pain: differences from placebo in mean change from baseline to endpoint in mean pain score were, 300 mg/d, 0.71 (P⫽.0009); 450 mg/d, -0.98, and 600 mg/d, -1.00 (each P⬍.0001). Significantly greater proportions of patients responded (ⱖ30% improvement) to pregabalin than placebo: 300, 42% (P⫽.0172); 450, 50% (P⫽.0002); 600 mg/d, 48% (P⫽.0006); placebo, 30%. Significant changes in mean pain score were evident as early as Week 1 and were sustained to endpoint. On the PGIC, there was statistically significant improvement for all pregabalin groups compared with placebo, with 68% of 300-, 78% of 450-, and 66% of 600-mg/d patients reporting at least minimal improvement vs 48% of placebo. On the FIQ, patients in the 450- and 600-mg/d groups showed statistically significant improvement vs placebo (treatment differences: 450 mg/d, -5.24, P⫽.0041; 600 mg/d, -5.34, P⫽.0034). The most common AEs were dizziness (all pregabalin, 35.8%; placebo, 7.6%) and somnolence (18.0%; 3.8%). Pregabalin, at all dosages, demonstrated rapid and sustained pain relief and at 450 and 600 mg/d demonstrated effective management of FMS.