New Drug Update 2009-2010 - LAFP

Observed cases 2.12 (95% CI, 1.33 to 3.38) c 2.32 (95% CI, 1.44 to 3.73) d
Fibromyalgia pain treatment
BOCF 1.5 (95% CI, 1.05 to 2.13) b 1.68 (95% CI, 1.18 to 2.38) c
LOCF 1.56 (95% CI, 1.11 to 2.19) c 1.9 (95% CI, 1.36 to 2.65) d
Observed cases 1.86 (95% CI, 1.27 to 2.73) d 2.49 (95% CI, 1.69 to 3.66) d
a CI = confidence interval; b P < 0.05 vs placebo.; c P ≤ 0.01 vs placebo.; d P ≤ 0.001 vs placebo.
Milnacipran was also assessed in a randomized, double-blind, placebo-controlled study enrolling 888
patients with fibromyalgia. The majority of patients were women (95.6%) and white (93.6%), with a mean
age of about 49 years and a mean duration of fibromyalgia of 5.6 years. Patients received placebo (223
patients), milnacipran 100 mg/day (224 patients), or milnacipran 200 mg/day (441 patients) for 27 weeks.
Patients were required to discontinue all centrally acting fibromyalgia therapies, including
antidepressants, sedative-hypnotics, muscle relaxants, and centrally acting analgesics, as well as
transcutaneous electrical nerve stimulation, biofeedback, tender and trigger point injections, acupuncture,
and anesthetic or narcotic patches. All analgesics were prohibited except acetaminophen, aspirin, stable
doses of NSAIDs, and limited doses of rescue hydrocodone. The primary efficacy end point for the
“treatment of fibromyalgia” was a composite defining responders as patients with at least 30% pain
improvement as assessed by the change from baseline in 24-hour morning recall pain collected from
daily e-diary scores, a rating of “very much improved” or “much improved” on the PGIC, and an at least 6-
point improvement from baseline in physical function (SF-36 Physical Component Summary score). The
primary end point measure for “treatment of pain of fibromyalgia” was a composite defining responders as
patients achieving at least 30% improvement in pain in 24-hour morning recall pain and rating themselves
as “very much improved” or “much improved” on the PGIC scale. Missing data were analyzed using
BOCF for the week-15 evaluation. At the week-27 assessment, BOCF was utilized for patients
prematurely discontinuing the study before week 15, and LOCF was used for patients who completed
week 15 but discontinued prior to week 27. Results for patients completing the study and those with
partial data are summarized in Table 4. Overall, in the modified intent-to-treat analysis, composite
responses were not consistently achieved in more milnacipran-treated patients at 3 months or at 6
months. Improvements were observed with milnacipran on the secondary end points of morning recall
pain scores (P = 0.01), real-time pain scores (P = 0.01), weekly recall pain scores (P = 0.018), PGIC (P <
0.001), multidimensional Fatigue Inventory total score (P = 0.016), the Multiple Ability Selfreport
Questionnaire (MASQ) cognition total score (P = 0.025), and multiple domains of the SF-36.
Improvements were not observed in sleep quality or quantity. Among subjects completing the study, the
composite pain response rate was 27.2% for placebo, 45.2% for milnacipran 100 mg/day, and 45.4% for
milnacipran 200 mg/day; however, dropout rates were 35% in the placebo group, 43% in the 100 mg/day
group, and 46% in the 200 mg/day group (J Rheumatol. 2009;36(2):398-409).
A randomized, blinded extension to this study enrolled 449 patients who were either maintained on
milnacipran 200 mg/day (209 patients) or re-randomized from placebo or milnacipran 100 mg/day to
milnacipran 100 mg/day (48 patients) or 200 mg/day (192 patients) for an additional 6 months of therapy.
Among patients re-randomized from placebo to milnacipran 200 mg/day, pain scores improved 47%
(mean pain score declined from 53.9 to 39.4). Among those continuing milnacipran, VAS pain scores
remained consistent (42 mm at week 27, 39.2 mm at week 38, 39.5 mm at week 44, and 38.6 mm at
week 52) and improvements on the PGIC and pain, stiffness, tiredness, and depressed mood times of the
Fibromyalgia Impact Questionnaire (FIQ) were maintained over 12 months. Sixty-seven percent of
patients completed the extension study (Arthritis Rheum. 2008;58(9)(suppl):S383).
Table 4. Composite Response Rates With Milnacipran in Patients With Fibromyalgia
Parameter Placebo (n =
223)
Milnacipran 100 mg/day (n =
224)
Milnacipran 200 mg/day (n =
441)
Fibromyalgia treatment (>/=30% pain decrease, a reduction in PGIC and SF 36)
Week 15
BOCF 12.1% 19.6% (P = 0.028) 19.3% (P = 0.017)
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