Fibromyalgia (FM)

EFFICACY IN FM
LYRICA (pregabalin) provided sustained FM pain relief in a 6-month pivotal trial1,2
6 month FM trial chart
Modified baseline observation carried forward (mBOCF) analysis of intent-to-treat population.
*Measured by the VAS score.
Measured by the PGIC scale.
In a pivotal study, more than half of LYRICA patients experienced sustained FM pain relief for 6 months vs one-third of patients on placebo1,2
LYRICA 300 mg/day, 450 mg/day, and 600 mg/day divided BID; 450 mg/day is the maximum recommended dose for FM patients.
Less pain and increased function may go hand-in-hand for patients with FM. In the same study, LYRICA improved patients’ ability to function significantly longer vs placebo (P=.0028), as measured by FIQ (secondary endpoint)
ǁImproved function based on time to LTR as measured by FIQ.
FIQ=Fibromyalgia Impact Questionnaire; LTR=loss of therapeutic response; PGIC=Patient Global Impression of Change; VAS=Visual Analog Scale.
Study description
Adapted from Crofford et al. Pain. 20081; Pfizer data on file.2
Results from a pivotal, multicenter, double-blind, placebo-controlled, randomized discontinuation trial conducted in 4 phases: baseline (1 week), open-label (6 weeks), double-blind (26 weeks), and follow-up (1 week). Patients were required to meet 1990 American College of Rheumatology criteria for FM (widespread pain for ≥3 months and pain in ≥11 of 18 tender points) and have scored their pain over the previous week as ≥40 mm on the 0-100 mm pain visual analog scale (VAS) at screening and baseline visits. Patients with conditions that could confound assessment of FM symptoms, with severe depression or other severe psychiatric or severe medical conditions, or who had previously participated in a LYRICA clinical trial, were excluded.
During the open-label phase, LYRICA was titrated to 300 mg/day, 450 mg/day, or 600 mg/day, divided BID, to optimize dose based on FM pain control and tolerability. There was no evidence that the 600 mg/day dose conferred additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended for FM. Patients were not permitted to use other FM treatments or agents that treat pain. Acetaminophen was allowed as a rescue medication (≤4 g/day).
Of the 1051 patients who were assigned to the open-label treatment phase, 663 (63%) completed the open-label phase; of those 663 patients, 566 (85%) were considered responders (defined as having a ≥50% reduction in pain VAS and a Patient Global Impression of Change [PGIC] score of “much improved” or “very much improved") and were randomized to the 6-month, double-blind treatment phase at their optimal fixed dosages, established during the open-label treatment phase.
The primary efficacy measure was time to loss of therapeutic response (LTR), defined as <30% reduction in pain VAS score compared with open-label baseline, worsening of symptoms necessitating a different treatment, or withdrawal from the study due to adverse reactions. Regardless of whether patients had primary LTR, all randomized patients were evaluated for secondary efficacy measures, including time to worsening of PGIC and Fibromyalgia Impact Questionnaire (FIQ) scores. The FIQ is a 20-item, validated, self-assessment tool used to measure the impact of symptoms and their changes from the previous week. The FIQ measures effects of pain, disturbed mood, and function, with scores between 0 and 100; higher scores indicate greater impairment.
LYRICA provided powerful relief from FM pain2,3
powerful FM trial chart
In a 14-week pivotal trial, patients who were titrated to 300 mg/day or 450 mg/day experienced significant FM pain relief vs patients on placebo.
LYRICA was administered in doses divided BID.
Less pain and increased function may go hand-in-hand for patients with FM. In the same trial, LYRICA 450 mg/day significantly improved some patients' ability to function vs placebo (P<.005), as measured by FIQ (secondary endpoint)2‡
LYRICA 300 mg/day did not demonstrate significant improvement in FIQ scores (P=.1078).
FIQ=Fibromyalgia Impact Questionnaire.
Study description
Adapted from Arnold et al. J Pain. 20083; Pfizer data on file.2
Results from a 14-week, randomized, double-blind, multiple-dose, placebo-controlled, multicenter study of 745 patients that evaluated the efficacy and safety of LYRICA in the treatment of FM. Patients were required to meet 1990 American College of Rheumatology criteria for FM and have scored their pain as ≥40 mm on the 0-100 mm pain visual analog scale at screening and baseline visits. Following a 1-week run-in phase that excluded patients with a high placebo response (≥30% decrease on the pain visual analog scale [VAS]), patients were randomized to receive LYRICA 300 mg/day, 450 mg/day, 600 mg/day, divided BID, or placebo. There was no evidence that the 600 mg/day dose conferred additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended for FM. Patients were not permitted to use other FM treatments or agents that treat pain. Acetaminophen ≤4 g/day was allowed as a rescue medication.
The primary outcome variable was the comparison of endpoint mean pain scores, derived from daily diary ratings of pain intensity (0 to 10 scale). Endpoint mean pain score was based on modified baseline observation carried forward (mBOCF). The mBOCF analysis censors patients who discontinue for adverse reactions (baseline score is carried forward) but includes the last observation carried forward (LOCF) for patients who discontinue for other reasons.
Change in Fibromyalgia Impact Questionnaire (FIQ) scores was a secondary efficacy measure. The FIQ is a 20-item, validated, self-assessment tool used to measure the impact of symptoms and their changes from the previous week. The FIQ measures effects of pain, disturbed mood, and function, with scores between 0 and 100; higher scores indicate greater impairment.
DOSING IN FIBROMYALGIA
Consider your next steps for LYRICA titration, based on efficacy and tolerability
dosing FM chart
Dosage may be increased to 300 mg/day based on efficacy and tolerability within 1 week
Patients may be titrated to 450 mg/day if they are not experiencing sufficient benefit with 300 mg/day
When discontinuing LYRICA, taper gradually over a minimum of 1 week
Adjust the LYRICA daily dose based on renal function
For adult patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment
Supplementary dosage following hemodialysis
  • Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg
  • Patients on the 25-50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg
  • Patients on the 50-75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg
  • Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg
The use of LYRICA in pediatric patients with compromised renal function has not been studied.
*Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.
Supplementary dose is a single additional dose.
SAFETY IN FIBROMYALGIA
In controlled trials in adults with FM,
Adverse reactions were generally mild to moderate2
safety in FM chart
safety in FM chart
safety in FM chart
In controlled FM trials
5.6% discontinuation rate for LYRICA vs <1% for placebo
  • Occurred within 1 to 3 days
  • Median duration: 17 days
  • Dizziness resolved by study end for 62% of patients
  • In some patients, dizziness persisted throughout the course of treatment
safety in FM chart
safety in FM chart
safety in FM chart
In controlled FM trials
3.4% discontinuation rate for LYRICA vs <1% for placebo
  • Occurred within 2 to 4 days
  • Median duration: 34 days
  • Somnolence resolved by study end for 44% of patients
  • In some patients, somnolence persisted throughout the course of treatment
safety in FM chart
safety in FM chart
safety in FM chart
In controlled FM trials of up to 14 weeks
1% discontinuation rate for LYRICA vs 0% for placebo
  • Mean weight gain: LYRICA 3.7 lb vs placebo 1.5 lb
  • Although weight gain was not associated with clinically important changes in blood pressure in these studies, the long-term cardiovascular effects of LYRICA-associated weight gain are unknown
In controlled LYRICA trials of up to 14 weeks:
  • Weight gain ≥7% of baseline body weight: LYRICA 9% vs placebo 2%
safety in FM chart
safety in FM chart
safety in FM chart
safety in FM chart
In controlled LYRICA trials
<1% of LYRICA patients discontinued due to peripheral edema vs <1% for placebo
  • Peripheral edema had no apparent association with:
    • Cardiovascular complications (eg, hypertension or congestive heart failure)
    • Laboratory changes in renal or hepatic function
These data are from short-term trials of patients without clinically significant heart or peripheral vascular disease. LYRICA should be used with caution in patients with congestive heart failure with New York Heart Association Class III and Class IV cardiac status.
safety in FM chart
safety in FM chart
LYRICA was administered in doses divided BID.
*Includes studied 600 mg/day dosage; 450 mg/day is the maximum recommended dose for patients with FM.
In these controlled FM trials2:
  • In all LYRICA-treated patients, dizziness (38% vs placebo 9%) and somnolence (20% vs placebo 4%) were the most frequent adverse reactions
In a post hoc analysis of the same controlled FM trials, at Week 12:
  • Onset or worsening of dizziness for LYRICA 300 mg/day was 27%; LYRICA 450 mg/day was 38%; placebo was 7%
  • Onset or worsening of somnolence for LYRICA 300 mg/day was 16%; LYRICA 450 mg/day was 17%; placebo was 3%
  • Onset or worsening of weight gain for LYRICA 300 mg/day was 2%; LYRICA 450 mg/day was 2%; placebo was <1%
Clinical Background
clinical background
With the Co-Pay Savings Card, eligible patients may pay as little as $4 per Rx for branded LYRICA.
 
See terms and conditions below for full eligibility requirements.
*Includes patients who received any study dose of LYRICA in placebo-controlled studies of fibromyalgia, painful diabetic peripheral neuropathy, postherpetic neuralgia, and neuropathic pain associated with spinal cord injury, as well as open-label extensions of those studies.
References: 1. Crofford LJ, Mease PJ, Simpson SL, et al. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008;136(3):419-431. 2. Data on file. Pfizer Inc., New York, NY. 3. Arnold LM, Russell IJ, Diri EW, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain. 2008;9(9):792-805.