L. M. Arnold¹, I. J. Russell², R. W. Duan³, H. Florian⁴, J. P. Young, Jr³, S. Martin⁵, G. Haig⁴, J. Barrett^6
1Women's Health Research Program, Dept of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, ²Clinical Research Center, University of Texas Health Science Center, San Antonio, ³Associate Director, ⁴Director, ⁵Outcomes Research, Pfizer Global R&D, Ann Arbor, ⁶Medical Director, Pfizer Global Pharmaceuticals, New York, United States

Background: Recent double-blind, randomized controlled trials (RCTs) have demonstrated that pregabalin is efficacious and well tolerated as treatment of pain and other symptoms associated with fibromyalgia syndrome (FMS).
Objectives: To provide additional insight into the efficacy of monotherapy with pregabalin (dosed twice daily) as treatment of FMS pain and associated symptoms.
Methods: The 2 trials employed a similar double-blind, placebo-controlled, parallel-group design. Patients meeting 1990 ACR criteria for FMS (widespread pain for at least 3 months and pain in at least 11 of 18 tender points) with pain VAS score of at least 40 mm (0-100–mm scale) and mean pain score of at least 4 (0-10 numeric rating scale) at randomization were eligible for randomization to pregabalin 300, 450, or 600 mg/d (twice daily) or placebo for 13 or 14 weeks (1- or 2-week dosage-escalation period followed by 12 weeks of fixed-dosage treatment). Primary efficacy parameter was endpoint mean pain score.
Results: 1493 patients were randomized: 368 to pregabalin 300 mg/d, 373 to 450 mg/d, 378 to 600 mg/d, and 374 to placebo. 91% were white, 94% were women, mean age was 49 years, median FMS duration was 9.7years, and baseline mean pain score was 6.9. Pregabalin significantly improved pain scores; differences from placebo in mean change from baseline to endpoint in pain score were: 300 mg/d, -0.55 (P=.0003); 450 mg/d, -0.71; 600 mg/d, -0.82 (each P<.0001). A dose response was evident, with treatment effect sizes increasing almost linearly from 300 to 450 to 600 mg/d. Pregabalin 450 and 600 mg/d were associated with significant improvements in total FIQ score: mean differences from placebo at endpoint were: 450 mg/d, -3.43 (P=.0116); 600 mg/d -3.05 (P=.0243). Mean treatment difference for 300 mg/d was -2.47 (P=.0707). A significantly greater proportion of patients treated with pregabalin reported clinically meaningful improvement on the PGIC (“much improved” or “very much improved”): 38% of 300 mg/d (P=.0002), 44% of 450 mg/d (P<.0001), and 45% of 600 mg/d patients (P<.0001) vs 29% of placebo patients. Pregabalin was generally well tolerated, and most adverse events (AEs) were mild to moderate in severity and tended to resolve with continued treatment. The most common treatment-emergent AEs among pregabalin-treated patients were dizziness (300 mg/d, 31%; 450 mg/d, 41%; 600 mg/d, 45%; placebo, 8%), somnolence (18%; 22%; 25%; 5%), and weight gain (11%; 11%; 14%; 2%). Among pregabalin patients, 18%, 22%, and 29% of those treated with 300, 450, and 600 mg/d discontinued because of AEs compared with 11% of placebo patients.

Conclusion: In this pooled analysis of almost 1500 patients with FMS, monotherapy treatment with pregabalin 300, 450, and 600 mg/d (twice daily) was associated with robust efficacy for the relief of pain associated with FMS. Pregabalin treatment was also associated with significant improvement in total FIQ score (450 and 600 mg/d) and in patients’ self ratings of their global improvement on the PGIC (all dosages).