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Authors and affiliations: L. J. Crofford, S. Simpson, J. P. Young, Jr., G. Haig, U. Sharma. University of Kentucky, Lexington, Kentucky (Crofford); Pfizer Global R&D, Ann Arbor, Michigan (Simpson, Young, Haig); MMS Holding Inc, Canton, Michigan (Sharma).

Purpose: Fibromyalgia Syndrome (FMS) affects approximately 2% to 5% of the U.S. population, and there is no FDA-approved treatment. Pregabalin is approved in the U.S. for the treatment of painful diabetic peripheral neuropathy and postherpetic neuralgia, and has demonstrated efficacy versus placebo (PBO) as monotherapy for FMS. The current study was designed to evaluate the durability of pregabalin's efficacy for relieving pain associated with FMS.

Methods: This PBO-controlled, double-blind (DB) trial consisted of a screening phase, during which patients washed out of prohibited medications; an open-label (OL) phase of 6 weeks, during which each patient's pregabalin dosage was adjusted to optimize pain control and tolerability (300, 450, or 600 mg/day); and a DB phase of 26 weeks, in which responding patients were randomized either to continue their pregabalin dosage or to PBO.

Patients who had =50% reduction in mean Pain VAS score from OL baseline and scored “much improved” or “very much improved” on the Patient Global Impression of Change (PGIC) at 2 of the final 3 visits in OL were eligible for randomization into the DB phase. The primary endpoint of the double-blind phase was time to loss of therapeutic response (LTR), defined as <30% reduction in VAS pain score (from OL baseline) during 2 consecutive visits or subjective worsening of Fibromyalgia symptoms.

Results: Of the 1,051 patients who entered the OL phase, 93% were female, and 88% were white, with a mean age of 50 years, median duration of FMS of 7.8 years, and baseline mean pain VAS score of 78 (out of 100). A total of 663 patients completed OL, and 566 were randomized to DB; 279 received pregabalin (at the optimal dosage established during OL), and 287 received PBO.

During the DB phase, time to LTR was significantly longer for patients treated with pregabalin compared with those receiving PBO (p<0.001). Based on Kaplan-Meier estimates of time-to-event comparing PBO patients with all pregabalin patients, 25% of PBO-treated patients lost therapeutic response by Day 7 compared with Day 34 for pregabalin-treated patients.

By the end of DB treatment, nearly twice as many PBO patients (174; 61%) had lost therapeutic response compared with pregabalin-treated patients (90; 32%). The most common adverse effects considered treatment related during OL were dizziness (36%) and somnolence (22%). In DB, the most common adverse effects that exceeded placebo were sinusitis (5% pregabalin, 3% PBO) and arthralgia and anxiety (5% pregabalin, 2% PBO).

Most adverse effects were mild or moderate in intensity. There were two deaths; neither was considered treatment related.

Conclusions: Pregabalin demonstrated durability of pain relief associated with FMS by significantly delaying time to loss of therapeutic response versus placebo.