Background: Pregabalin has demonstrated efficacy in reducing pain associated with FMS in previous trials of up to 14 weeks’ duration. Though pain is the cardinal symptom of fibromyalgia syndrome (FMS), patients typically report a variety of associated symptoms, including fatigue and sleep disturbance.
Objectives: This trial was designed to evaluate the durability of patients’ response over time to pregabalin for relief of FMS-associated pain and commonly associated symptoms, including fatigue and sleep disturbance.
Methods: Patients who met 1990 ACR criteria for FMS were eligible for enrollment in this multiphase, double-blind, placebo-controlled randomized discontinuation trial. The trial included a 1-week screening period, a 6-week open-label (OL) period (during which patients’ optimal dosages of pregabalin 300, 450, or 600 mg/d were established), and a 26-week double-blind (DB) period. Patients who completed the 6-week OL period and who had a ≥50% reduction in mean pain VAS score from OL baseline and a Patient Global Impression of Change (PGIC) rating of at least “much improved” were eligible for randomization to pregabalin (optimized OL dosage of 300, 450, or 600 mg/d) or placebo. Primary endpoint of the 26-week DB period was time to loss of therapeutic response (LTR), defined as <30% reduction (from OL baseline) in pain VAS score during 2 consecutive visits or subjective worsening of fibromyalgia (eg, patient needs alternative therapy). The Multidimensional Assessment of Fatigue (MAF) and the Medical Outcomes Study (MOS)-Sleep Scale were included as secondary endpoints to evaluate time to LTR for associated fatigue and sleep disturbance. All analyses evaluated all dosages of pregabalin as a single group versus placebo.
Results: 1051 patients entered the OL treatment period, of which 663 completed, and 566 met DB inclusion criteria and were randomized. 279 patients were assigned to pregabalin and 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. Nearly twice as many placebo patients had LTR by end of DB (174; 61%) compared with pregabalin patients (90; 32%, P<.0001). Worsening of fatigue (as measured by the MAF) occurred by Day 27 in half the placebo group compared with by Day 119 for pregabalin (P<.0001). Half of placebo patients showed worsening in the Overall Sleep Problems Index of the MOS-Sleep Scale by Day 14 vs by Day 42 for pregabalin (P<.0001). The most common adverse events (AEs) during OL were dizziness (36%) and somnolence (22%). During DB treatment, the most common AEs exceeding placebo were sinusitis (pregabalin, 5% vs placebo, 3%) and arthralgia and anxiety (5% vs 2%).

Conclusion: Pregabalin demonstrated a durable therapeutic effect for relief of pain, fatigue, and sleep disturbance associated with FMS in patients who received pregabalin treatment for as long as 32 weeks.