Background
Methods
Inclusion and exclusion criteria
Literature search
Data extraction
Outcome measure
Statistical analysis
Results
Literature search
Study | Treatment | n | Mean age (yrs) | Baseline WOMAC score (SD) | Change from baseline WOMAC score (SD) | Percentage women | Duration OA at baseline (yrs) | Flare required | Concomitant analgesic allowedd
| OA site |
---|---|---|---|---|---|---|---|---|---|---|
Abou-Raya et al. 2012 [49]b
| Duloxetine | 144 | 68.9 | 50.63 (9.56) | -12.40 (14.02) | 16 | 5.7 | No | Yes | Knee |
Placebo | 144 | 68.5 | 50.94 (9.47) | -3.96 (15.24) | 17 | 5.6 | ||||
Afilalo et al. 2010 [50]f
| Oxycodone 40–100 mg | 342 | 58.2 | -27.50 (21.75) | 59 | No | Not mentioned | Knee | ||
Study NCT00421928 | Placebo | 337 | 58.2 | -22.50 (21.00) | 59 | |||||
Baerwald et al. 2010 [51]b
| Naproxen 1000 mg | 156 | 62.26 | -22.54 (20.40) | 32.1 | Yes | No | Hip | ||
Placebo | 331 | 63.29 | -14.80 (22.27) | 37.2 | ||||||
Bensen et al. 1999 [52] | Celecoxib 200 mg | 202 | 63 | 53.13 (17.08) | -12.50 (18.06) | 72 | 9 | No | No | Knee |
Naproxen 1000 mg | 198 | 62 | 55.10 (14.58) | -12.40 (18.91) | 71 | 10 | ||||
Placebo | 203 | 62 | 53.85 (15.42) | -6.35 (16.18) | 75 | 11 | ||||
Bingham et al. 2007a [53] | Etoricoxib 30 mg | 231 | 62.1 | 65.40 (13.03) | -24.37 (21.37) | 66.2 | Yes | No | Hip/knee | |
Celecoxib 200 mg | 241 | 62.5 | 66.20 (13.24) | -22.21 (21.66)a
| 69.7 | |||||
Placebo | 127 | 62.8 | 64.67 (13.30) | -10.98 (22.14)a
| 65.4 | |||||
Bingham et al. 2007b [53] | Etoricoxib 30 mg | 244 | 61.9 | 67.23 (13.24) | -24.37 (22.19) | 69.7 | Yes | No | Hip/knee | |
Celecoxib 200 mg | 247 | 62.2 | 65.59 (14.59) | -23.19 (23.29)a
| 61.9 | |||||
Placebo | 117 | 60.9 | 64.98 (13.81) | -12.29 (22.63)a
| 65 | |||||
Boswell et al. 2008 [54] | Celecoxib 200 mg | 185 | 59.7 | 63.55 (14.70) | -23.46 (24.51)a
| 67 | 8.8 | No | No | Knee |
Placebo | 186 | 60.5 | 63.37 (13.68) | -18.46 (23.46)a
| 73 | 8 | ||||
Burch et al. 2007 [55]f
| Tramadol 200–300 mg | 432 | 62 | 34.96 (14.74)g
| 64 | Yes | No | Knee | ||
Study NCT00833794 | Placebo | 214 | 62 | 35.20 (15.13)g
| 62 | |||||
Chappell et al. 2011 [26]b
| Duloxetine 60–120 mg | 128 | 63.16 | 51.63 (10.45) | -20.50 (11.87) | 70 | 8.14 | No | Yes | Knee |
Study NCT00433290 | Placebo | 128 | 61.9 | 53.82 (9.04) | -16.25 (12.26) | 84 | 6.74 | |||
Chappell et al. 2009 [27]b
| Duloxetine 60–120 mg | 111 | 62.07 | 57.10 (12.15) | -24.01 (16.07) | 63.06 | 9.04 | No | Yes | Knee |
Study NCT00408421 | Placebo | 120 | 62.48 | 56.51 (11.12) | -16.81 (13.67) | 67.5 | 9.3 | |||
Clegg et al. 2006 [56]b, e
| Celecoxib 200 mg | 318 | 59.4 | 47.10 (13.36) | -17.95 (14.98) | 66.7 | 10.1 | No | Yes | Knee |
Placebo | 313 | 58.2 | 46.23 (13.49) | -14.58 (15.99) | 63.9 | 9.5 | ||||
DeLemos et al. 2011 [57] | Tramadol 200 mg | 199 | 62 | 61.13 (14.02) | -16.24 (24.22) | 62.3 | 8.5 | No | No | Hip/knee |
Tramadol 300 mg | 199 | 59.7 | 60.37 (15.93) | -22.10 (24.16) | 61.8 | 7.6 | ||||
Celecoxib 200 mg | 202 | 60 | 58.21 (15.26) | -25.60 (24.58) | 64.9 | 8 | ||||
Placebo | 200 | 58.9 | 59.95 (15.49) | -17.73 (24.28) | 68.5 | 7.8 | ||||
Essex et al. 2012 [58]c
| Celecoxib 200 mg | 296 | 60 | 56.15 (15.42) | -23.13 (19.71) | 64.9 | 7.2 | Yes | No | Knee |
Naproxen 1000 mg | 293 | 60.7 | 56.56 (15.73) | -23.54 (19.61) | 67.6 | 8.5 | ||||
Fishman et al. 2007 [59] | Tramadol 200 mg | 107 | 61 | 58.42 (13.99) | -24.39 (21.19)a
| 59.8 | No | Yes | Knee | |
Tramadol 300 mg | 105 | 60 | 63.74 (15.21) | -25.54 (44.61) | 65.7 | |||||
Placebo | 224 | 61 | 61.29 (14.16) | -18.82 (38.32) | 61.6 | |||||
Fleischmann et al. 2006 [60]b
| Celecoxib 200 mg | 444 | 61.3 | 50.94 (16.76) | -16.67 (18.95) | 67.1 | 6.7 | No | No | Knee |
Placebo | 231 | 61.5 | 48.65 (16.97) | -9.69 (16.82) | 66.2 | 6.6 | ||||
Fleischmann et al. 2001 [61]b
| Tramadol 200–400 mg | 63 | 62.52 | 41.60 (20.50)g
| 65.1 | 7.94 | Yes | No | Knee | |
Placebo | 66 | 62.45 | 50.40 (22.50)g
| 59.1 | 7.76 | |||||
Gana et al. 2006 [36] | Tramadol 200 mg | 201 | 59.1 | 63.77 (13.14) | -21.25 (23.92) | 63.7 | 7.7 | No | No | Hip/knee |
Tramadol 300 mg | 201 | 58.5 | 60.10 (14.73) | -20.27 (23.81) | 59.2 | 8 | ||||
Placebo | 205 | 56.4 | 61.82 (14.82) | -14.19 (23.45) | 68.8 | 7.7 | ||||
Hochberg et al. 2011a [62] | Celcoxib 200 mg | 242 | 33.2 | -5.56 (40.51)a, h
| 61.2 | Yes | Yes | Knee | ||
Placebo | 124 | 32.7 | 66.1 | |||||||
Hochberg et al. 2011b [62] | Celecoxib 200 mg | 244 | 33 | -4.36 (41.89)a, h
| 62.7 | Knee | ||||
Placebo | 122 | 33 | 63.1 | |||||||
Kivitz et al. 2002 [63] | Naproxen 1000 mg | 205 | 60.4 | 55.91 | -18.79 (19.78) | 63 | 9.4 | No | No | Knee |
Placebo | 205 | 60.3 | 55.72 | -14.04 (19.71) | 64 | 8.3 | ||||
Kivitz et al. 2001 [64] | Celecoxib 200 mg | 207 | 62 | 52.29 (16.73) | -10.10 (15.92) | 65 | 7.2 | Yes | No | Hip |
Naproxen 1000 mg | 207 | 64 | 51.88 (17.24) | -11.98 (16.07) | 66 | 7.3 | ||||
Placebo | 218 | 64 | 52.81 (15.60) | -4.38 (15.70) | 67 | 7.9 | ||||
Lehmann et al. 2005 [65]b
| Celecoxib 200 mg | 420 | 62.9 | 52.60 (14.93) | -15.31 (16.47) | 68.3 | 4.4 | Yes | yes | Knee |
Placebo | 424 | 61.7 | 51.77 (15.09) | -11.77 (19.03) | 71.9 | 3.9 | ||||
Leung et al. 2002 [66] | Etoricoxib 60 mg | 224 | 62.93 | 63.84 (13.89) | -22.19 (15.91) | 77.2 | 5.88 | Yes | No | Hip/knee |
Naproxen 1000 mg | 221 | 63.16 | 63.76 (13.36) | -21.91 (15.81) | 78.3 | 6.25 | ||||
Placebo | 56 | 64.09 | 68.11 (10.83) | -13.26 (15.17) | 82.1 | 6.3 | ||||
Markenson et al. 2005 [67]b, e
| Oxycodone 10–120 mg | 56 | 62 | 64.70 (15.71)a
| -14.93 (26.09) | 68 | No | Yes | Hip/knee/spine/other | |
Placebo | 51 | 64 | 63.80 (15.00) | -0.87 (19.72) | 78 | |||||
Puopolo et al. 2007 [68] | Etoricoxib 30 mg | 224 | 62.1 | 64.95 | -24.90 (23.14) | 77.7 | 6.6 | Yes | Yes | Hip/knee |
Ibuprofen 2400 mg | 213 | 62.3 | 63.18 | -21.73 (22.49) | 73.7 | 6.7 | ||||
Placebo | 111 | 64 | 64.56 | -14.43 (21.23) | 75.7 | 6.5 | ||||
Rauck et al. 2013 [69] | Hydromorphone 16 mg | 330 | 59.5 | -17.00 (19.98) | 64.2 | No | Yes | Hip/knee | ||
Placebo | 331 | 60 | -13.00 (20.01) | 63 | ||||||
Schnitzer et al. 2011 [70]b
| Celecoxib 200 mg | 419 | 61.7 | 54.90 (14.49) | -16.58 (15.24)a
| 61.3 | 3.7 | No | No | Hip |
Placebo | 416 | 61.4 | 54.58 (15.11) | -10.62 (13.83)a
| 60.6 | 3.8 | ||||
Schnitzer et al. 2011 [71]b
| Naproxen 1000 mg | 254 | 60 | -26.29 (18.71)a
| 70.5 | Yes | No | Knee | ||
Placebo | 257 | 60.15 | -16.04 (18.62)a
| 72.65 | ||||||
Schnitzer et al. 2010 [72]b
| Naproxen 1000 mg | 227 | 61.1 | 70.08 (12.98) | -33.33 (20.23)a
| 67.4 | Yes | No | Knee | |
Placebo | 221 | 61 | 69.85 (13.12) | -20.42 (20.17)a
| 71.9 | |||||
Sheldon et al. 2005 [73]b
| Celecoxib 200 mg | 393 | 60.2 | 54.79 (15.45) | -16.25 (19.08) | 63.1 | 6.7 | No | No | Knee |
Placebo | 382 | 60.8 | 55.31 (14.36) | -9.90 (17.01) | 61.3 | 7 | ||||
Sowers et al. 2005 [74]c
| Celecoxib 200 mg | 136 | 61.8 | 46.20 (22.16) | -16.30 (20.99) | 62 | No | No | Hip/knee | |
Naproxen 1000 mg | 128 | 63.6 | 51.40 (20.36) | -14.70 (21.50) | 60 | |||||
Tannenbaum et al. 2004 [75]b
| Celecoxib 200 mg | 481 | 64.1 | 50.73 (16.04) | -13.96 (16.46) | 69.2 | 5.3 | No | No | Knee |
Placebo | 243 | 64.6 | 51.25 (14.58) | -9.79 (16.77) | 67.1 | 4.3 | ||||
Vojtassak et al. 2011 [76] | Hydromorphone | 138 | 65 | 60.00 (10.11) | -17.75 (14.62) | 77 | No | Yes | Hip/knee | |
Placebo | 149 | 66 | 57.92 (10.36) | -17.69 (15.79) | 68 | |||||
Wiesenhutter et al. 2005 [77] | Etoricoxib 30 mg | 214 | 63.1 | 68.68 (16.64) | -24.52 (22.97) | 70.1 | 7.9 | Yes | No | Hip/Knee |
Ibuprofen 2400 mg | 210 | 61.3 | 68.13 (17.02) | -23.65 (23.13) | 70 | 8.2 | ||||
Placebo | 104 | 59.5 | 69.71 (16.52) | -14.20 (20.24) | 72.1 | 6.9 |
Treatment | Total n | Mean age (yrs) | Mean percentage women | Mean duration of OA (yrs) |
---|---|---|---|---|
Duloxetine | 383 | 65.00 | 73.25 | 7.48 |
Ibuprofen | 423 | 61.80 | 71.86 | 7.44 |
Naproxen | 1889 | 61.73 | 68.41 | 8.26a
|
Celecoxib | 4681 | 61.63 | 65.60 | 6.58a
|
Etoricoxib | 1137 | 62.41 | 72.12 | 6.78a
|
Tramadol | 1507 | 60.60 | 62.67 | 7.95a
|
Oxycodone | 398 | 58.73 | 60.27 | NR |
OROS hydromorphone | 468 | 59.5b
| 67.97 | NR |
Placebo | 6560 | 61.26b
| 66.97 | 6.78a
|
Study | Randomization appropriatea
| Treatment allocation concealmentb
| Groups similar at baselinec
| Blinding of all participantsd
| Unexpected imbalance in drop-outse
| Measured outcomes not reportedf
| ITT analysis, missing datag
| Quality scoreh
|
---|---|---|---|---|---|---|---|---|
Abou-Raya et al. 2012 [49] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Afilalo et al. 2010 [50] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Baerwald et al. 2010 [51] | Not clear | Not clear | Yes | Yes | No | No | Yes | 5 |
Bensen et al. 1999 [52] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Bingham et al. 2007 [53] | Not clear | Not clear | Yes | Yes | No | No | Yes | 5 |
Boswell et al. 2008 [54] | Not clear | Not clear | Yes | Yes | No | No | Yes | 5 |
Burch et al. 2007 [55] | Yes | Yes | Yes | Yes | No | No | Not clear | 6 |
Chappell et al. 2011 [26] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Chappell et al. 2009 [27] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Clegg et al. 2006 [56] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
DeLemos et al. 2011 [57] | Not clear | Yes | Yes | Yes | No | No | Yes | 6 |
Essex et al. 2012 [58] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Fishman et al. 2007 [59] | Yes | Yes | Yes | Yes | Yes, explained | No | Yes | 6 |
Fleischmann et al. 2006 [60] | Not clear | Yes | Yes | Yes | No | No | Yes | 6 |
Fleischmann et al. 2001 [61] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Gana et al. 2006 [36] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Hochberg et al. 2011 [62] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Kivitz et al. 2002 [63] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Kivitz et al. 2001 [64] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Lehmann et al. 2005 [65] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Leung et al. 2002 [66] | Yes | Yes | Yes | Yes | No | Yes | Not clear | 5 |
Markenson et al. 2005 [67] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Puopolo et al. 2007 [68] | Yes | Not clear | Yes | Yes | No | No | Not clear | 5 |
Rauck et al. 2013 [69] | not clear | Yes | Yes | Yes | No | No | Yes | 6 |
Schnitzer et al. 2011 [70] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Schnitzer et al. 2011 [71] | Not clear | Not clear | Yes | Yes | No | No | Yes | 5 |
Schnitzer et al. 2010 [72] | Yes | Not clear | Yes | Yes | No | No | Yes | 6 |
Sheldon et al. 2005 [73] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Sowers et al. 2005 [74] | Yes | Not clear | Yes | Yes | No | No | Yes | 6 |
Tannenbaum et al. 2004 [75] | Not clear | Yes | Yes | Yes | No | No | Yes | 6 |
Vojtassak et al. 2011 [76] | Yes | Yes | Yes | Yes | No | No | Yes | 7 |
Wiesenhutter et al. 2005 [77] | Not clear | Yes | Yes | Yes | No | No | Yes | 6 |
Statistical results
Duloxetine | Ibuprofen | Naproxen | Celecoxib | Etoricoxib | Tramadol | Oxycodone | Hydromorphone | |
---|---|---|---|---|---|---|---|---|
Frequentist analysis
| ||||||||
Number of studies | 3 | 2 | 7f
| 14f
| 5 | 5 | 2 | 2 |
Change from baseline vs. placebo, mean | -6.48 | -8.34 | -8.27 | -5.78 | -11.04 | -3.99 | -8.56 | -2.13 |
95% CI | [-9.09, -3.88] | [-11.98, -4.71] | [-10.27, -6.28] | [-6.86, -4.69] | [-13.24, -8.84] | [-6.74, -1.23] | [-17.23, 0.11] | [-5.99, 1.72] |
I2 (%) | 44.35 | 0 | 51.92 | 32.49 | 0 | 58.03 | 71.99 | 63.54 |
Indirect vs. Duloxetine a
| NA | -1.86 | -1.93 | 0.71 | -4.56 | 2.36 | -2.07 | 4.35 |
95% CIb
| NA | [-6.33, 2.62] | [-4.70, 0.84] | [-2.12, 3.53] | [-7.97, -1.15] | [-1.00, 5.73] | [-11.13, 6.98] | [-0.31, 9.01] |
Bayesian analysis
| ||||||||
Number of studies contributing to each compoundc
| 3 | 2 | 9 | 16 | 5 | 5 | 2 | 2 |
Change from baseline vs. placebo, meand
| -6.47 | -7.85 | -7.9 | -6.2 | -9.53 | -2.89 | -7.04 | -2.19 |
95% CI | [-9.27, -3.7] | [-11.59, -4.18] | [-9.54, -6.27] | [-7.46, -5.03] | [-11.86, -7.3] | [-5.41, -0.54] | [-11.35, -2.95] | [-5.52, 1.21] |
Indirect vs. Duloxetinea
| NA | -1.38 | -1.43 | 0.27 | -3.07 | 3.57 | -0.58 | 4.28 |
95% CIb
| NA | [-6.04, 3.21] | [-4.65, 1.81] | [-2.78, 3.28] | [-6.66, 0.49] | [-0.17, 7.19] | [-5.69, 4.32] | [-0.01, 8.69] |
Probability Duloxetine is Superior
|
NA
|
0.28
|
0.19
|
0.57
|
0.04
|
0.97
|
0.41
|
0.97
|
Number of studies contributing to each compound for adjusted for baseline WOMAC scoree
| 3 | 2 | 7 | 14 | 5 | 3 | 1 | 1 |
Indirect vs. Duloxetine adjusted for baseline WOMAC scoree
| NA | 1.85 | 0.24 | 0.83 | -0.43 | 4.92 | -4.67 | 8.19 |
95% CIb
| NA | [-2.13, 5.9] | [-2.36, 2.87] | [-1.45, 3.14] | [-3.4, 2.57] | [1.51, 8.34] | [-13.24, 4.07] | [3.84, 12.56] |
Probability Duloxetine is Superior
|
NA
|
0.82
|
0.57
|
0.76
|
0.38
|
1
|
0.15
|
1
|
Random effects | ||
---|---|---|
Model | DIC | Heterogeneity SD |
Without adjustment |
128.29
| 1.62 |
Without adjustment excluding studies with no baseline score |
107.00
| 1.53 |
With adjustment | ||
Baseline |
93.85
| 0.59 |
Flare |
105.32
| 1.52 |
Analgesic use |
105.88
| 1.09 |