Introduction
Methods
Overview
Eligibility criteria
Study design
Outcome measures
Primary efficacy outcomes
Secondary efficacy outcomes
Health outcomes
Safety outcomes
Statistical analyses
Results
Patient disposition and characteristics
Placebo (n = 195) | Duloxetine (n = 191) |
p Value | |
---|---|---|---|
Age, yr | 49.5 ± 11.7 | 47.8 ± 12.0 | 0.1373a
|
Females | 164 (84.1) | 157 (82.2) | 0.6837 |
Weight, kg | 56.28 ± 10.47 | 58.00 ± 11.23 | 0.1219a
|
Height, cm | 159.61 ± 7.76 | 159.41 ± 7.40 | 0.7922 |
Major depressive disorder diagnosis | 7 (3.6) | 8 (4.2) | 0.7980 |
Duration of fibromyalgia, yr | 5.7 ± 6.6 | 5.5 ± 5.9 | 0.6968 |
Number of tender points | 15.5 ± 2.3 | 15.4 ± 2.3 | 0.8740 |
BPI average pain score (0–10) | 6.13 ± 1.35 | 6.05 ± 1.29 | 0.5456 |
FIQ total score (0–100) | 56.82 ± 16.14 | 55.95 ± 16.25 | 0.5950 |
BDI-II total score (0–63) | 14.89 ± 9.62 | 15.34 ± 9.73 | 0.6533 |
Efficacy and health outcomes
Variable | Placebo (n = 195) | Duloxetine (n = 191) | Difference (95 % CI) |
p Value | ||
---|---|---|---|---|---|---|
Baseline | Change | Baseline | Change | |||
BPI average pain score | ||||||
MMRM | 6.13 ± 1.35 | −1.58 ± 0.23 | 6.05 ± 1.29 | −1.90 ± 0.23 | −0.32 (−0.70, 0.06) | 0.0988 |
LOCF | 6.13 ± 1.35 | −1.22 ± 0.26 | 6.05 ± 1.29 | −1.60 ± 0.26 | −0.38 (−0.74, −0.02) | 0.0408a
|
BOCF | 6.13 ± 1.35 | −0.92 ± 0.25 | 6.05 ± 1.29 | −1.38 ± 0.25 | −0.45 (−0.81, −0.10) | 0.0132a
|
WOCF | 6.13 ± 1.35 | −0.88 ± 0.26 | 6.05 ± 1.29 | −1.35 ± 0.26 | −0.47 (−0.84, −0.10) | 0.0132a
|
BPI other pain | ||||||
Worst | 7.44 ± 1.40 | −1.35 ± 0.26 | 7.36 ± 1.28 | −1.91 ± 0.26 | −0.56 (−0.99, −0.12) | 0.0126a
|
Least | 4.46 ± 1.81 | −1.23 ± 0.22 | 4.68 ± 1.70 | −1.72 ± 0.22 | −0.49 (−0.87, −0.12) | 0.0092a
|
Right now | 5.90 ± 1.69 | −1.20 ± 0.26 | 5.99 ± 1.52 | −1.77 ± 0.26 | −0.57 (−1.00, −0.15) | 0.0083a
|
Patient diary | ||||||
Average pain | 5.98 ± 1.39 | −1.48 ± 0.18 | 5.79 ± 1.35 | −1.82 ± 0.18 | −0.33 (−0.70, 0.03) | 0.0755 |
Worst pain | 7.23 ± 1.28 | −1.34 ± 0.19 | 7.05 ± 1.24 | −1.81 ± 0.19 | −0.47 (−0.88, −0.06) | 0.0232a
|
BPI interference scores | ||||||
General activities | 5.82 ± 2.31 | −1.76 ± 0.32 | 5.82 ± 2.14 | −2.22 ± 0.31 | −0.46 (−0.98, 0.06) | 0.0807 |
Mood | 5.33 ± 2.53 | −1.42 ± 0.33 | 5.65 ± 2.40 | −2.17 ± 0.32 | −0.75 (−1.29, −0.22) | 0.0057a
|
Walking ability | 4.08 ± 2.85 | −1.29 ± 0.30 | 4.29 ± 2.73 | −1.67 ± 0.29 | −0.38 (−0.84, 0.09) | 0.1114 |
Normal work | 5.50 ± 2.46 | −1.76 ± 0.32 | 5.61 ± 2.42 | −2.18 ± 0.31 | −0.42 (−0.94, 0.09) | 0.1081 |
Relationships with people | 3.54 ± 2.97 | −0.53 ± 0.30 | 3.90 ± 2.89 | −1.09 ± 0.30 | −0.55 (−1.04, −0.07) | 0.0264a
|
Sleep | 5.22 ± 2.91 | −1.57 ± 0.36 | 5.30 ± 2.81 | −1.82 ± 0.35 | −0.24 (−0.81, 0.32) | 0.3959 |
Enjoyment of life | 5.13 ± 2.75 | −1.24 ± 0.32 | 5.12 ± 2.65 | −1.90 ± 0.31 | −0.66 (−1.18, −0.15) | 0.0119a
|
Average of all 7 items | 4.95 ± 2.09 | −1.44 ± 0.27 | 5.10 ± 2.07 | −1.95 ± 0.27 | −0.52 (−0.96, −0.07) | 0.0222a
|
FIQ | ||||||
Physical functioning | 3.85 ± 2.32 | −0.37 ± 0.26 | 3.36 ± 2.35 | −0.84 ± 0.25 | −0.47 (−0.86, −0.09) | 0.0160a
|
Feeling good | 7.11 ± 2.73 | −0.79 ± 0.41 | 7.17 ± 2.72 | −1.59 ± 0.40 | −0.80 (−1.39, −0.21) | 0.0082a
|
Missing work | 2.44 ± 2.79 | −0.48 ± 0.28 | 2.33 ± 3.09 | −0.97 ± 0.27 | −0.49 (−0.93, −0.06) | 0.0270a
|
Housework | 5.86 ± 2.39 | −1.69 ± 0.36 | 5.86 ± 2.45 | −2.14 ± 0.35 | −0.45 (−0.97, 0.08) | 0.0932 |
Pain | 7.01 ± 1.67 | −1.76 ± 0.35 | 6.83 ± 1.52 | −2.37 ± 0.34 | −0.62 (−1.11, −0.12) | 0.0148a
|
Fatigue | 7.27 ± 2.08 | −1.45 ± 0.35 | 7.08 ± 1.97 | −1.96 ± 0.34 | −0.52 (−1.03, 0.00) | 0.0479a
|
Morning tiredness | 6.81 ± 2.41 | −1.68 ± 0.39 | 6.86 ± 2.40 | −1.80 ± 0.37 | −0.13 (−0.69, 0.44) | 0.6618 |
Stiffness | 6.26 ± 2.56 | −1.59 ± 0.35 | 6.20 ± 2.57 | −2.10 ± 0.34 | −0.51 (−1.03, 0.02) | 0.0577 |
Anxiety | 5.43 ± 2.67 | −1.18 ± 0.36 | 5.33 ± 2.59 | −1.86 ± 0.35 | −0.68 (−1.20, −0.15) | 0.0114a
|
Depression | 4.79 ± 2.71 | −0.96 ± 0.35 | 4.91 ± 2.76 | −1.62 ± 0.34 | −0.66 (−1.18, −0.14) | 0.0129a
|
Total score | 56.82 ± 16.14 | −13.05 ± 2.65 | 55.95 ± 16.25 | −18.41 ± 2.57 | −5.35 (−9.26, −1.45) | 0.0073a
|
SF-36 | ||||||
Physical functioning | 62.51 ± 19.82 | 3.04 ± 2.15 | 63.72 ± 18.75 | 7.40 ± 2.13 | 4.36 (1.35, 7.37) | 0.0046a
|
Physical role limitations | 49.13 ± 25.60 | 0.44 ± 2.98 | 49.25 ± 25.57 | 8.20 ± 2.96 | 7.76 (3.57, 11.94) | 0.0003a
|
Bodily pain | 36.60 ± 11.71 | 5.28 ± 2.08 | 36.53 ± 12.40 | 10.95 ± 2.07 | 5.67 (2.76, 8.59) | 0.0002a
|
General health perceptions | 38.76 ± 14.77 | 3.31 ± 1.94 | 39.37 ± 17.67 | 6.55 ± 1.92 | 3.25 (0.53, 5.96) | 0.0192a
|
Vitality | 31.96 ± 18.80 | 3.35 ± 2.53 | 32.43 ± 21.03 | 10.05 ± 2.51 | 6.70 (3.15, 10.25) | 0.0002a
|
Social functioning | 55.71 ± 26.54 | 3.28 ± 3.06 | 55.76 ± 27.53 | 10.32 ± 3.04 | 7.04 (2.74, 11.34) | 0.0014a
|
Emotional role limitations | 61.24 ± 26.80 | −3.63 ± 3.36 | 60.34 ± 29.16 | 5.50 ± 3.35 | 9.12 (4.41, 13.83) | 0.0002a
|
Mental health | 56.10 ± 19.84 | −2.00 ± 2.52 | 55.50 ± 18.85 | 5.91 ± 2.51 | 7.91 (4.39, 11.43) | <0.0001a
|
CGI-Ib
| – | 3.27 ± 0.16 | – | 2.83 ± 0.15 | −0.44 (−0.71, −0.18) | 0.0012a
|
PGI-Ib
| – | 3.32 ± 0.16 | – | 2.83 ± 0.16 | −0.49 (−0.76, −0.22) | 0.0003a
|
BDI-II score (0–63) | 14.89 ± 9.62 | −1.19 ± 0.85 | 15.34 ± 9.73 | −4.09 ± 0.84 | −2.90 (−4.37, −1.44) | 0.0001a
|
ACR 2010 | ||||||
WPI (0–19) | 12.08 ± 3.57 | −1.06 ± 0.60 | 12.14 ± 3.58 | −2.34 ± 0.58 | −1.28 (−2.12, −0.44) | 0.0029a
|
SS (0–12) | 6.59 ± 1.88 | −1.00 ± 0.28 | 6.60 ± 1.82 | −1.37 ± 0.27 | −0.36 (−0.79, 0.06) | 0.0906 |
Total (0–31) | 18.67 ± 4.53 | −2.24 ± 0.77 | 18.74 ± 4.36 | −3.88 ± 0.74 | −1.64 (−2.74, −0.54) | 0.0037a
|
Week | Direct effect | Indirect effect |
---|---|---|
Week 2a
| 84.3 | 15.7 |
Week 4a
| 83.8 | 16.2 |
Week 6a
| 63.1 | 36.9 |
Week 10a
| 43.2 | 56.8 |
Week 14a
| 41.6 | 58.4 |
Endpointb
| 28.3 | 71.7 |
Safety and tolerability
Placebo (n = 196) | Duloxetine (n = 194) |
p Valuea
| |
---|---|---|---|
AEs | 123 (62.8) | 148 (76.3) | 0.0042b
|
ADRs | 70 (35.7) | 125 (64.4) | <0.0001b
|
Serious AEs | 1 (0.5) | 1 (0.5) | 1.000 |
Serious ADRs | 0 (0.0) | 1 (0.5) | 0.4974 |
Discontinuations due to AEs | 15 (7.7) | 14 (7.2) | 1.000 |
Discontinuations due to ADRs | 10 (5.1) | 14 (7.2) | 0.4077 |
AEs by preferred term | |||
Somnolence | 21 (10.7) | 51 (26.3) | <0.0001b
|
Nausea | 9 (4.6) | 42 (21.6) | <0.0001b
|
Constipation | 8 (4.1) | 29 (14.9) | 0.0002b
|
Nasopharyngitis | 29 (14.8) | 26 (13.4) | 0.7715 |
Dry mouth | 7 (3.6) | 14 (7.2) | 0.1218 |
Decreased appetite | 1 (0.5) | 13 (6.7) | 0.0008b
|
Dizziness | 2 (1.0) | 11 (5.7) | 0.0112b
|
Headache | 6 (3.1) | 9 (4.6) | 0.4437 |
Fatigue | 6 (3.1) | 9 (4.6) | 0.4437 |
Diarrhea | 7 (3.6) | 8 (4.1) | 0.7990 |