New Drug Update 2009-2010 - LAFP

Observed
cases
17.3% 32.8% (P = 0.003) 32.8% (P < 0.001)
Week 27
BOCF/LOCF 13% 18.3% (P = 0.245) 18.1% (P = 0.105)
Observed
cases
19.4% 33.3% (P = 0.056) 31.9% (P = 0.017)
Fibromyalgia pain treatment (>/= 30% reduction in pain scores)
Week 15
BOCF 19.3% 27.2% (P = 0.056) 26.8% (P = 0.032)
Observed
cases
27.2% 45.2% (P = 0.003) 45.4% (P < 0.001)
Week 27
BOCF/LOCF 18.4% 25.9% (P = 0.072) 25.6% (P = 0.034)
Observed
cases
27.9% 43.8% (P = 0.021) 45.2% (P = 0.001)
Another randomized, double-blind, phase 3 study that assessed milnacipran 200 mg/day compared with
placebo in 884 patients with fibromyalgia was reported in a meeting abstract. The majority of patients
were women (94.3%), with a mean age of 48.8 years. Patients received placebo (449 patients) or
milnacipran 200 mg/day (435 patients) for 12 weeks. The primary end point, fibromyalgia composite
response, was defined as patients with at least 30% improvement in 24-hour recall pain and a rating of
“very much improved” or “much improved” on the PGIC scale. Overall impact on symptomatology was
assessed with the FIQ total score. Milnacipran exhibited greater improvement relative to placebo in the
composite response (P = 0.0003; results not provided) and in the FIQ total score (P = 0.015). Greater
improvement with milnacipran than placebo was also observed for secondary end points, including
weekly pain on e-diary, Brief Pain Inventory (BPI), SF-36 Mental and Physical components,
Multidimensional Fatigue Inventory total score, FIQ physical function subscale score, and the MASQ
cognition total score (Eur Neuropsychopharmacol. 2008;18(suppl 4):S574-S575).
Milnacipran was also evaluated in a randomized, double-blind, dose-escalation study enrolling 125
patients with fibromyalgia. Mean age was 46.2 to 48 years; 96% to 98% of patients in each treatment
group were women, and 79% to 89% were white. The mean duration of fibromyalgia ranged from 3.8 to
4.3 years, and most patients had used multiple nondrug treatment modalities (eg, acupuncture,
antiepileptics, chiropractic, diet, exercise, hot-cold packs, massage, physical therapy). Patients were
assigned to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months using a3:3:2
ratio. All previous antidepressants, centrally acting muscle relaxants, hypnotics, and opioids and their
derivations had to be discontinued over a period of 1 to 4 weeks. Stable doses of NSAIDs, aspirin, and
acetaminophen were allowed during the study. Following a 2-week baseline observation period, patients
were randomized to therapy with placebo (28 patients), milnacipran 25 mg once daily (46 patients), or
milnacipran 12.5 mg twice daily (51 patients). If doses were tolerated, dose escalation was completed
weekly to 50, 100, and then 200 mg once daily, or 25, 50, and then 100 mg twice daily over a 4-week
period. Patients were then continued at a stable dose for an additional 8 weeks. There was no difference
in the rate of discontinuation of drug therapy (30.4% with milnacipran once daily, 27.5% with milnacipran
twice daily, and 25% with placebo). Dose escalation to the target dose of 200 mg was achieved in 92% of
patients assigned twice-daily administration and 81% of those assigned once-daily administration. The
mean daily dose of milnacipran was 174 mg in the once-daily group and 191 mg in the twice-daily group.
The primary end point was the change in pain recorded on e-diary during the final 2 weeks of the trial
compared with the average pain scores during the 2-week baseline period. All analysis was intent-to-treat
with LOCF. Improvements in pain, global well-being, and fatigue were observed in both active-treatment
groups; however, twice-daily administration was associated with more improvements compared with
placebo. Pain scores are summarized in Table 5. Response was defined as a 30% or 50% reduction in
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