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A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese fibromyalgia patients.

Murakami M, Osada K, Mizuno H, Ochiai T, Alev L, Nishioka K - Arthritis Res. Ther. (2015)

Bottom Line: Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses.Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL.Duloxetine treatment was safe and well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan. murakami.masato@nihon-u.ac.jp.

ABSTRACT

Introduction: Fibromyalgia is characterized by widespread pain and is often accompanied by accessory symptoms. There are limited treatment options for this condition in Japan. Therefore, we conducted a phase III study to assess the efficacy and safety of duloxetine in Japanese patients with fibromyalgia.

Methods: This randomized, double-blind, placebo-controlled, parallel-group trial was conducted in Japan. Outpatients who met the American College of Rheumatology 1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain score was ≥4 were randomized to duloxetine 60 mg or placebo once daily for 14 weeks. The primary efficacy measure was the change in the BPI average pain score from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and last observation carried forward (LOCF) analysis of covariance were used to evaluate the primary efficacy measure.

Results: Overall, 393 patients were randomized to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM analysis revealed no significant difference between duloxetine and placebo regarding the change in BPI average pain scores at week 14. Based on LOCF analysis, a statistically significant improvement in the change in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo. Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses. The treatment was generally well tolerated. Somnolence, nausea, and constipation were the most common treatment-emergent adverse events in the duloxetine group. The discontinuation rates due to treatment-emergent adverse events were similar in both groups.

Conclusions: Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was safe and well tolerated. These results suggest that duloxetine treatment could be associated with improvements in pain relief and QoL in Japanese patients with fibromyalgia.

Trial registration: ClinicalTrials.gov Identifier: NCT01552057 . Registered 9 March 2012.

No MeSH data available.


Related in: MedlinePlus

Changes in Brief Pain Inventory average, worst, least, and right now pain scores from baseline. Values are means at each time point. *p < 0.05 vs. placebo. Dashed lines, placebo; black solid lines, duloxetine. LOCF last observation carried forward; LS least squares
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Fig3: Changes in Brief Pain Inventory average, worst, least, and right now pain scores from baseline. Values are means at each time point. *p < 0.05 vs. placebo. Dashed lines, placebo; black solid lines, duloxetine. LOCF last observation carried forward; LS least squares

Mentions: Although there was no statistically significant difference between the duloxetine and placebo groups in the reduction of the BPI average pain score at week 14 (p = 0.0988) in the MMRM analysis, a statistically significant improvement in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo when we used the LOCF ANCOVA approach (Table 2, Fig. 3). The post hoc BOCF and WOCF analyses also showed that the change in average pain score was significantly greater in the duloxetine group (both p = 0.0132) than in the placebo group (Table 2). Analyses of the proportion of responders with pain reduction ≥30 % (p = 0.0130) or ≥50 % (p = 0.0318) and the sustained response rate (p = 0.0139) in the BPI average pain score indicated that the reduction in pain was significantly greater in the duloxetine group than in the placebo group (Fig. 4).Table 2


A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese fibromyalgia patients.

Murakami M, Osada K, Mizuno H, Ochiai T, Alev L, Nishioka K - Arthritis Res. Ther. (2015)

Changes in Brief Pain Inventory average, worst, least, and right now pain scores from baseline. Values are means at each time point. *p < 0.05 vs. placebo. Dashed lines, placebo; black solid lines, duloxetine. LOCF last observation carried forward; LS least squares
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4546310&req=5

Fig3: Changes in Brief Pain Inventory average, worst, least, and right now pain scores from baseline. Values are means at each time point. *p < 0.05 vs. placebo. Dashed lines, placebo; black solid lines, duloxetine. LOCF last observation carried forward; LS least squares
Mentions: Although there was no statistically significant difference between the duloxetine and placebo groups in the reduction of the BPI average pain score at week 14 (p = 0.0988) in the MMRM analysis, a statistically significant improvement in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo when we used the LOCF ANCOVA approach (Table 2, Fig. 3). The post hoc BOCF and WOCF analyses also showed that the change in average pain score was significantly greater in the duloxetine group (both p = 0.0132) than in the placebo group (Table 2). Analyses of the proportion of responders with pain reduction ≥30 % (p = 0.0130) or ≥50 % (p = 0.0318) and the sustained response rate (p = 0.0139) in the BPI average pain score indicated that the reduction in pain was significantly greater in the duloxetine group than in the placebo group (Fig. 4).Table 2

Bottom Line: Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses.Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL.Duloxetine treatment was safe and well tolerated.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan. murakami.masato@nihon-u.ac.jp.

ABSTRACT

Introduction: Fibromyalgia is characterized by widespread pain and is often accompanied by accessory symptoms. There are limited treatment options for this condition in Japan. Therefore, we conducted a phase III study to assess the efficacy and safety of duloxetine in Japanese patients with fibromyalgia.

Methods: This randomized, double-blind, placebo-controlled, parallel-group trial was conducted in Japan. Outpatients who met the American College of Rheumatology 1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain score was ≥4 were randomized to duloxetine 60 mg or placebo once daily for 14 weeks. The primary efficacy measure was the change in the BPI average pain score from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and last observation carried forward (LOCF) analysis of covariance were used to evaluate the primary efficacy measure.

Results: Overall, 393 patients were randomized to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM analysis revealed no significant difference between duloxetine and placebo regarding the change in BPI average pain scores at week 14. Based on LOCF analysis, a statistically significant improvement in the change in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo. Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses. The treatment was generally well tolerated. Somnolence, nausea, and constipation were the most common treatment-emergent adverse events in the duloxetine group. The discontinuation rates due to treatment-emergent adverse events were similar in both groups.

Conclusions: Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was safe and well tolerated. These results suggest that duloxetine treatment could be associated with improvements in pain relief and QoL in Japanese patients with fibromyalgia.

Trial registration: ClinicalTrials.gov Identifier: NCT01552057 . Registered 9 March 2012.

No MeSH data available.


Related in: MedlinePlus