Pregabalin, typically used to treat nerve pain or seizures, appears to offer extended pain relief for those with fibromyalgia, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

Fibromyalgia is an often misunderstood syndrome that causes widespread chronic muscle pain and tenderness in 2 percent of the U.S. population, most commonly women. In addition to pain, fibromyalgia is often associated with fatigue, sleep disturbances and memory problems. Unfortunately, to date, no FDA-approved treatment has been available for this syndrome.

Researchers enrolled 1,051 participants in a six-week program of 300, 450 or 600 mg daily doses of pregabalin to optimize pain control and medication tolerance. On average, the population was 93% female, 88% white, had endured fibromyalgia for over seven years and measured their pain severity as 78 on a 100 point scale.

At the end of the 6-week program, 663 participants (63%) cited over 50% reduction in pain, and being "much" or "very much improved." Of these, 566 were randomized into a 26-week double-blind study to receive either pregabalin at the optimal dosage established during the 6 weeks prior or placebo. The primary goal of this six-month study, one of the longest control studies conducted to date, was to determine how long their therapeutic responses lasted.

One-fourth of placebo-treated patients saw worsening by day 7 as compared to day 34 for those on medication. By the end of the double-blind treatment, nearly twice (61%) as many placebo patients had lost response as compared to 32% of the patients on medication. The most common side effects of pregabalin were dizziness, somnolence, sinusitis, joint pain and anxiety. One death occurred each in the placebo and treatment arms of the trial, but neither was treatment-related.

"Fibromyalgia is a common and often debilitating pain syndrome," explains Leslie J. Crofford, MD, Gloria W. Singletary Professor of Rheumatology & Women's Health, University of Kentucky, Lexington, Kentucky, and an investigator in the study. "The results of this six-month study indicate pregabalin has a significant benefit in terms of longer-term pain relief for these patients."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Presentation Number: L44

A Six-month, Double-blind, Placebo-controlled, Durability of Effect Study of Pregabalin for Pain Associated With Fibromyalgia

L. J. Crofford1, S. Simpson2, J. P. Young, Jr2, G. Haig2, U. Sharma3. 1University of Kentucky, Lexington, KY; 2Pfizer Global R&D, Ann Arbor, MI; 3MMS Holding Inc, Canton, MI

Purpose: Fibromyalgia syndrome (FMS) affects approximately 2-5% of the US population, and there is no FDA-approved treatment. Pregabalin is approved in the US 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 1051 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 AEs considered treatment related during OL were dizziness (36%) and somnolence (22%). In DB, the most common AEs that exceeded placebo were sinusitis (5% pregabalin, 3% PBO) and arthralgia and anxiety (5% pregabalin, 2% PBO). Most AEs were mild or moderate in intensity. There were two deaths; neither were considered treatment related.

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

Disclosure Block: L.J. Crofford, Pfizer, Wyeth, 2; Pfizer, Wyeth, Orphan, Allergan, Merck, 5; S. Simpson, Pfizer Inc, 1; Pfizer Inc, 3; J.P. Young, Pfizer Inc, 1; Pfizer Inc, 3; G. Haig, Pfizer Inc, 1; Pfizer Inc, 3; U. Sharma, Pfizer Inc, 1; Pfizer Inc, 5.

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