title: Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin.
abstract: This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and 40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1-3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4-6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had 50% decrease in pain VAS and a self-rating of "much" or "very much" improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient's optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P<.0001). Kaplan-Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain.
authors.affiliation: University of Kentucky, Internal Medicine, Room J-503 Kentucky Clinic, 740 S. Limestone Street, Lexington, KY 40536-0284, USA Seattle Rheumatology Associates, Seattle, WA, USA Pfizer Global Research & Development, Ann Arbor, MI, USA MMS Holdings Inc., Canton, MI, USA.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Susan L
authors.initials: SL
authors.lastname: Simpson
authors.forename: James P
authors.initials: JP
authors.lastname: Young
authors.forename: Susan A
authors.initials: SA
authors.lastname: Martin
authors.forename: George M
authors.initials: GM
authors.lastname: Haig
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000700:Analgesics / Q000008:administration & dosage; D002985:Clinical Protocols; D002986:Clinical Trials as Topic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015990:Placebo Effect; D000069583:Pregabalin; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid