Presentation: Pregabalin Therapy for Durability of Meaningful Relief of Fibromyalgia (2007)

1522 Pregabalin Therapy for Durability of Meaningful Relief of Fibromyalgia

Objectives:
The purpose of the trial (FREEDOM) was to evaluate pregabalin (300-600mg/d) for durability of effect in reducing pain associated with Fibromyalgia (FM).
Methods:
This randomized, placebo-controlled, double-blind study consisted of a 1-week screening phase; a 6-week open-label phase (individualized pregabalin dosage optimization to 300, 450, or 600 mg/d); and a 26-week double-blind phase. Patients who had ≥50% 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 FM. Fibromyalgia Impact Questionnaire (FIQ), Multidimensional Assessment of Fatigue (MAF), and Medical Outcomes Study (MOS) Sleep Scale (all scored 0-100) from open-label baseline were also assessed.
Results
1051 patients entered open-label: 93% were female, 88% were white; mean age=50 years, FMS median duration=7.8 years, and baseline mean pain VAS score=78 mm. 663 patients completed open-label; 566 were randomized: 279 to pregabalin, 287 to placebo. Time to LTR for pain was significantly longer for pregabalin vs placebo (P<.0001): based on Kaplan-Meier estimates of time-to-event, 25% of placebo patients had LTR by Day 7, compared with LTR by Day 34 for pregabalin patients. Time to LTR, by dose, was significantly longer for pregabalin patients compared to placebo (300mg/d, 122 vs 4 days; 450mg/d, 25 vs 7 days, and 600mg/d, 26 vs 7 days). Significant improvement was demonstrated for the FIQ in terms of delayed worsening for the total score (14 vs 19 days) and all subscales, including “physical impairment”, “work missed”, “do job”, and “anxiety and depression” (all P<.0001). Time to worsening was significantly delayed for pregabalin-treated subjects compared to placebo for MAF (27 vs 119 days, P<.0001). For MOS-Sleep significant benefit in delayed time to worsening was shown in 4/5 domains (“sleep disturbance”, “awake short of breath”, “sleep adequacy”, “Sleep Problems Index” [all P<.0001], and “somnolence”, P=.0003). 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%).
Conclusions
Pregabalin significantly delayed time to LTR. Pregabalin was effective for relief of pain and improvement of functional status and fatigue associated with FM as demonstrated by the FIQ, MAF, and MOS Sleep. Pregabalin was safe and generally well-tolerated in patients with fibromyalgia.
The trials reported here were funded by Pfizer Inc.

  S. Simpson, Pfizer Employee, 3; J.P. Young, Pfizer Employee, 3; G. Haig, Pfizer Employee, 3; J. Barrett, Pfizer Employee, 3.