Efficacy of long-term milnacipran treatment in patients meeting different thresholds of clinically relevant pain relief: subgroup analysis of a randomized, double-blind, placebo-controlled withdrawal study

Figures & data

Figure 1 Overview of milnacipran studies.

Abbreviations: DB, double-blind; MLN, milnacipran; OL, open-label.

Figure 2 Distribution of pain response at randomization in patients who received milnacipran ≥100 mg/day during the prior long-term, open-label study.

Table 1 Mean scores prior to milnacipran exposure and at study randomizationa

	≥50% pain reduction (protocol-defined responders)		≥30% to 50% pain reduction (nonresponder subgroup)		<30% pain reduction (nonresponder subgroup)
	Placebo (n=50)	Milnacipran (n=100)	Placebo (n=18)	Milnacipran (n=43)	Placebo (n=36)	Milnacipran (n=74)
VAS pain, mean (SD)
Pre-milnacipranb	66.2 (14.7)	65.4 (13.0)	68.8 (14.6)	65.9 (12.4)	64.7 (14.6)	64.0 (15.4)
Randomization	19.3 (11.6)	16.6 (9.6)	41.6 (12.2)	38.7 (8.7)	59.1 (15.4)	62.0 (14.0)
FIQR, mean (SD)
Pre-milnacipranc	NA	NA	NA	NA	NA	NA
Randomization	21.4 (15.8)	19.5 (11.9)	31.4 (15.8)	35.4 (15.8)	43.0 (17.9)	43.9 (18.4)
SF-36 PCS, mean (SD)
Pre-milnacipranb	32.6 (7.7)	35.1 (8.1)	33.3 (8.0)	32.0 (6.7)	33.7 (7.5)	32.7 (7.8)
Randomization	41.3 (10.2)	41.6 (8.4)	36.4 (8.4)	34.6 (8.4)	35.9 (7.6)	32.2 (8.9)
BDI, mean (SD)
Pre-milnacipranb	9.5 (6.6)	9.7 (6.8)	11.8 (12.1)	9.4 (6.4)	12.1 (7.9)	10.5 (8.2)
Randomization	4.8 (5.6)	3.1 (4.2)	4.8 (5.6)	6.3 (5.6)	9.6 (8.5)	8.0 (6.5)

Notes:

a Table describes the effects of long-term, open-label, milnacipran treatment in patients who were subsequently randomized to discontinue treatment (placebo) or continue treatment (milnacipran) in the current study

b baseline value from lead-in study prior to first milnacipran exposure, with post-hoc analysis conducted for all groups (ie, including the protocol-defined responders)

c as FIQR was not assessed in previous lead-in milnacipran studies, no pre-milnacipran baseline value is available.

Abbreviations: BDI, Beck Depression Inventory; FIQR, Fibromyalgia Impact Questionnaire-Revised; NA, not applicable; SD, standard deviation; SF-36 PCS, 36-Item Short-Form Health Survey Physical Component Summary; VAS, visual analog scale.

Figure 3 Mean changes from pre-milnacipran exposure in VAS pain scores.

Notes: The group with ≥50% pain reduction at randomization represents the protocol-defined responder population of the randomized withdrawal study; *P<0.05 versus milnacipran; **P<0.01; ***P<0.001.
Abbreviations: MLN, milnacipran; VAS, visual analog scale.

Table 2 Mean changes from randomization to end of the 12-week withdrawal period

Mean change (SD)	≥50% pain reduction (protocol-defined responders)			≥30% to <50% pain reduction (nonresponder subgroup)			<30% pain reduction (nonresponder subgroup)
	Placebo (n=50)	Milnacipran (n=100)	Difference	Placebo (n=18)	Milnacipran (n=43)	Difference	Placebo (n=36)	Milnacipran (n=74)	Difference
VAS pain	17.7 (24.2)	8.3 (18.7)	9.4b	8.5 (16.8)	−0.5 (18.4)	9.0a	−1.1 (13.7)	−5.3 (18.6)	4.2
FIQR total	12.0 (18.1)	4.8 (12.7)	7.2c	3.7 (14.8)	1.9 (14.0)	1.8	6.9 (13.4)	−2.8 (12.2)	9.7c
SF-36 PCS	−4.5 (6.3)	−2.1 (7.1)	−2.4b	−0.2 (10.7)	−0.7 (6.1)	0.5	−2.5 (6.6)	0.5 (5.8)	−3.0
BDI total	0.4 (3.3)	0.3 (3.0)	0.1	0.8 (3.3)	−0.2 (2.6)	1.0	0.3 (4.9)	−1.6 (4.8)	1.9

Notes:

a P<0.05 for treatment difference (placebo–milnacipran) within the subgroup

b P<0.01

c P<0.001.

Abbreviations: BDI, Beck Depression Inventory; FIQR, Fibromyalgia Impact Questionnaire-Revised; SD, standard deviation; SF-36 PCS, 36-Item Short-Form Health Survey Physical Component Summary; VAS, visual analog scale.

Figure 4 Mean change from randomization in Fibromyalgia Impact Questionnaire-Revised total scores in (A) ≥30% to <50% pain reduction subgroup and (B) <30% pain reduction subgroup.

Notes: *P<0.05 versus milnacipran; **P<0.01; ***P<0.001.