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Opiáceos transdérmicos u orales para la artrosis de rodilla o cadera

Información

DOI:
https://doi.org/10.1002/14651858.CD003115.pub4Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 17 septiembre 2014see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Salud musculoesquelética

Copyright:
  1. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Bruno R da Costa

    Correspondencia a: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

    [email protected]

  • Eveline Nüesch

    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

  • Rahel Kasteler

    Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

  • Elaine Husni

    Department of Rheumatic and Immunologic Diseases, Cleveland Clinic: Orthopedic and Rheumatologic Institute, Cleveland, USA

  • Vivian Welch

    Bruyere Research Institute, University of Ottawa, Ottawa, Canada

  • Anne WS Rutjes

    Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

  • Peter Jüni

    Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

Contributions of authors

Protocol completion: Nüesch, Rutjes, Husni, Jüni.
Acquisition of data: Nüesch, da Costa, Kasteler, Rutjes.
Analysis and interpretation of data: Nüesch, da Costa, Kasteler, Husni, Welch, Rutjes, Jüni.
Manuscript preparation: Nüesch, da Costa, Kasteler, Husni, Welch, Rutjes, Jüni.
Statistical analysis: Nüesch, da Costa, Rutjes, Jüni.

Drs. Nüesch and da Costa contributed equally to this review.

Sources of support

Internal sources

  • Institute of Social and Preventive Medicine, University or Bern, Switzerland.

    Intramural grants

External sources

  • Swiss National Science Foundation, Switzerland.

    National Research Program 53 on musculoskeletal health (grant numbers 4053‐40‐104762/3 and 3200‐066378)

  • Marie Curie Intra‐European Fellowship, Other.

    Dr Nüesch was recipient of a Marie Curie Intra‐European Fellowship for Career Development (grant number FP7‐PEOPLE‐2010‐IEF‐273673)

Declarations of interest

None.

Acknowledgements

We thank the Cochrane Musculoskeletal editorial team for valuable comments and Malcolm Sturdy for database support. The authors are grateful to Hans Quiding for providing us with additional information concerning design and outcome data.

Version history

Published

Title

Stage

Authors

Version

2014 Sep 17

Oral or transdermal opioids for osteoarthritis of the knee or hip

Review

Bruno R da Costa, Eveline Nüesch, Rahel Kasteler, Elaine Husni, Vivian Welch, Anne WS Rutjes, Peter Jüni

https://doi.org/10.1002/14651858.CD003115.pub4

2009 Oct 07

Oral or transdermal opioids for osteoarthritis of the knee or hip

Review

Eveline Nüesch, Anne WS Rutjes, Elaine Husni, Vivian Welch, Peter Jüni

https://doi.org/10.1002/14651858.CD003115.pub3

2009 Jul 08

Oral or transdermal opioids for osteoarthritis of the knee or hip

Protocol

Eveline Nüesch, Anne WS Rutjes, Elaine Husni, Vivian Welch, Peter Jüni

https://doi.org/10.1002/14651858.CD003115.pub2

2001 Apr 23

Opioid therapy for treating osteoarthritis pain

Protocol

Elaine Husni, V Welch, Lee Simon, Beverley Shea, Joan Peterson, Peter Tugwell, George A Wells, Jessie L McGowan, Vivian Robinson

https://doi.org/10.1002/14651858.CD003115

Differences between protocol and review

The cut‐off to distinguish between short‐term and long‐term trials was changed from 26 weeks to one month. Six months was considered to be rather long as the cut‐off for an agent that is not considered to be a structure‐modifying drug. In the absence of definitions for short‐term treatment in osteoarthritis treatment guidelines, we used the median follow‐up duration in the trials included in the first review (four weeks) as a cut‐off to discriminate between trials of shorter and longer duration.
We did not include the electronic database CINAHL in our search update since, in our previous search, this database did not identify any additional hits. Finally, we did not include the OARSI database in our search update, as we no longer had access to this database. We added analyses stratified by type of osteoarthritis (hip only versus knee only versus mixed) upon request of peer reviewers.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow chart.
Figuras y tablas -
Figure 1

Study flow chart.

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Methodological characteristics of included trials. (+) indicates low risk of bias, (?) unclear, and (‐) a high risk of bias on a specific item.
Figuras y tablas -
Figure 2

Methodological characteristics of included trials. (+) indicates low risk of bias, (?) unclear, and (‐) a high risk of bias on a specific item.

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Forest plot of 22 trials comparing the effects of any type of opioids and control (placebo or no intervention) on knee or hip pain. Values on x‐axis denote standardised mean differences. The plot is stratified according to type of opioids. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the standard error was inflated and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. Data relating to the 3, 3, 3, 2, 2, and 2 active intervention arms in Caldwell 2002, Chindalore 2005, Kivitz 2006, Matsumoto 2005, Hartrick 2009, and Etropolski 2011, respectively, were pooled.
Figuras y tablas -
Figure 3

Forest plot of 22 trials comparing the effects of any type of opioids and control (placebo or no intervention) on knee or hip pain. Values on x‐axis denote standardised mean differences. The plot is stratified according to type of opioids. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the standard error was inflated and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. Data relating to the 3, 3, 3, 2, 2, and 2 active intervention arms in Caldwell 2002, Chindalore 2005, Kivitz 2006, Matsumoto 2005, Hartrick 2009, and Etropolski 2011, respectively, were pooled.

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Funnel plot for effects on knee or hip pain.
 Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs.
Figuras y tablas -
Figure 4

Funnel plot for effects on knee or hip pain.
Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs.

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Standardised mean differences of knee or hip pain (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.
Figuras y tablas -
Figure 5

Standardised mean differences of knee or hip pain (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.

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Forest plot of 12 trials comparing the effects of any type of opioids and control (placebo or no intervention) on function. Values on x axis denote standardised mean differences. The plot is stratified according to type of opioids. Matsumoto 2005 contributed with two comparisons and the standard error was inflated and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. Data relating to the 3, 3, and 2 active intervention arms in Caldwell 2002, Kivitz 2006, and Matsumoto 2005, respectively, were pooled.
Figuras y tablas -
Figure 6

Forest plot of 12 trials comparing the effects of any type of opioids and control (placebo or no intervention) on function. Values on x axis denote standardised mean differences. The plot is stratified according to type of opioids. Matsumoto 2005 contributed with two comparisons and the standard error was inflated and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. Data relating to the 3, 3, and 2 active intervention arms in Caldwell 2002, Kivitz 2006, and Matsumoto 2005, respectively, were pooled.

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Funnel plot for effects on functioning of the knee or hip.
 Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs
Figuras y tablas -
Figure 7

Funnel plot for effects on functioning of the knee or hip.
Numbers on x axis refer to standardised mean differences (SMDs), on y axis to standard errors of SMDs

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Standardised mean differences of function (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.
Figuras y tablas -
Figure 8

Standardised mean differences of function (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.

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Forest plot of 10 trials comparing participants experiencing any adverse event between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis.
Figuras y tablas -
Figure 9

Forest plot of 10 trials comparing participants experiencing any adverse event between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis.

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Risk ratios of participants experiencing any adverse event between opioids and control groups (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.
Figuras y tablas -
Figure 10

Risk ratios of participants experiencing any adverse event between opioids and control groups (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.

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Forest plot of 21 trials comparing participants withdrawn or dropped out because of adverse events between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. The risk ratio in one trial could not be estimated because no withdrawals or drop‐outs because of adverse events occurred in either group.
Figuras y tablas -
Figure 11

Forest plot of 21 trials comparing participants withdrawn or dropped out because of adverse events between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. Matsumoto 2005, Hartrick 2009, Afilalo 2010, Etropolski 2011, and NCT00486811 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis. The risk ratio in one trial could not be estimated because no withdrawals or drop‐outs because of adverse events occurred in either group.

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Risk ratios of participants withdrawn or dropped out because of adverse events between opioids and control groups (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.
Figuras y tablas -
Figure 12

Risk ratios of participants withdrawn or dropped out because of adverse events between opioids and control groups (y axis) are plotted against total daily dose of morphine equivalents (x axis). The size of the circles is proportional to the random‐effects weights that were used in the meta‐regression. The dotted line indicates predicted treatment effects (regression line) from univariable meta‐regression by using daily morphine equivalence doses the explanatory variable, and dashed lines represent the 95% confidence intervals.

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Forest plot of three trials comparing participants experiencing any serious adverse event between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. The risk ratio in one trial could not be estimated because no serious adverse event occurred in either group.
Figuras y tablas -
Figure 13

Forest plot of three trials comparing participants experiencing any serious adverse event between any opioid and control (placebo or no intervention). Values on x axis denote risks ratios. The plot is stratified according to type of opioid. The risk ratio in one trial could not be estimated because no serious adverse event occurred in either group.

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Forest plot of 4 comparisons in three trials comparing participants experiencing withdrawal symptoms between any opioid and control (placebo or no intervention). Values on x axis denote odds ratios. The plot is stratified according to type of opioid. Afilalo 2010 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis.
Figuras y tablas -
Figure 14

Forest plot of 4 comparisons in three trials comparing participants experiencing withdrawal symptoms between any opioid and control (placebo or no intervention). Values on x axis denote odds ratios. The plot is stratified according to type of opioid. Afilalo 2010 contributed with two comparisons and the number of participants in the placebo group was halved to avoid duplicate counting of participants when including both comparisons in the overall meta‐analysis.

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Comparison 1 Opioids versus placebo, Outcome 1 Pain.
Figuras y tablas -
Analysis 1.1

Comparison 1 Opioids versus placebo, Outcome 1 Pain.

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Comparison 1 Opioids versus placebo, Outcome 2 Function.
Figuras y tablas -
Analysis 1.2

Comparison 1 Opioids versus placebo, Outcome 2 Function.

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Comparison 1 Opioids versus placebo, Outcome 3 Number of participants experiencing any adverse event.
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Analysis 1.3

Comparison 1 Opioids versus placebo, Outcome 3 Number of participants experiencing any adverse event.

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Comparison 1 Opioids versus placebo, Outcome 4 Number of participants who withdrew because of adverse events.
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Analysis 1.4

Comparison 1 Opioids versus placebo, Outcome 4 Number of participants who withdrew because of adverse events.

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Comparison 1 Opioids versus placebo, Outcome 5 Number of participants experiencing any serious adverse event.
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Analysis 1.5

Comparison 1 Opioids versus placebo, Outcome 5 Number of participants experiencing any serious adverse event.

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Comparison 1 Opioids versus placebo, Outcome 6 Withdrawal symptoms.
Figuras y tablas -
Analysis 1.6

Comparison 1 Opioids versus placebo, Outcome 6 Withdrawal symptoms.

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Summary of findings for the main comparison. Oral or transdermal opioids compared with placebo for osteoarthritis of the knee or hip

Oral or transdermal opioids compared with placebo for osteoarthritis of the knee or hip

Patient or population: participants with osteoarthritis of the knee or hip

Settings: various orthopaedic or rheumatology clinics

Intervention: oral or transdermal opioids

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Opioids

Pain intensity

Various pain scales.

(median follow‐up: 4 weeks)

‐1.8 cm change
on 10‐cm VAS1

29% improvement

‐2.5 cm change
(Δ ‐0.7 cm, ‐0.9 to ‐0.5)2

41% improvement
(Δ 12%, 9% to 15%)3

SMD ‐0.28 (‐0.35 to ‐0.20)

8275
(22)

++++
high

NNTB 10 (95% CI 8 to 14)4

Function

Various validated function scales.

(median follow‐up: 5 weeks)

‐1.2 units
on WOMAC (range 0 to 10)1

21% improvement

‐1.8 units on WOMAC
(Δ ‐0.6, ‐0.8 to ‐0.4)5

32% improvement
(Δ 11%, 7% to 14%)6

SMD ‐0.26 (‐0.35 to ‐0.17)

3553
(12)

++++
high

NNTB 12 (95% CI 10 to 18)7

Number of participants experiencing any adverse event

(median follow‐up: 8 weeks)

150 per 1000 participant‐years8

224 per 1000 participant‐years
(203 to 245)

RR 1.49 (1.35 to 1.63)

4898
(9)

+++O
moderate9

NNTH 14 (95% CI 11 to 19)

Number of participants who withdrew because of adverse events

(median follow‐up: 6 weeks)

17 per 1000 participant‐years8

64 per 1000 participant‐years
(50 to 82)

RR 3.76 (2.93 to 4.82)

7712
(19)

++++
high

NNTH 21 (95% CI 15 to 30)

Number of participants experiencing any serious adverse event

(median follow‐up: 8 weeks)

4 per 1000 participant‐years8

13 per 1000 participant‐years
(3 to 54)

RR 3.35 (0.83 to 13.56)

681
(3)

++OO
low10

Little evidence of harmful effect (NNTH not statistically significant)

Withdrawal symptoms

(median follow‐up: 16 weeks)

9 per 1000 participant‐years11

24 per 100
participant‐years
(18 to 33)

OR 2.67 (2.02 to 3.77)

1151
(3)

+++O
moderate12

NNTH 65 (95% CI 42 to 110)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; GRADE: GRADE Working Group grades of evidence (see explanations); NNTB: number needed to treat for an additional beneficial outcome; NNTH: number needed to treat for an additional harmful outcome; OR: odds ratio; RR: risk ratio; SMD: standardised mean difference; WOMAC: Western Ontario and McMaster Universities Arthritis Index.

GRADE Working Group grades of evidence
High quality (++++): Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality (+++O): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality (++OO): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality (+OOO): We are very uncertain about the estimate.

1 Median reduction as observed across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).
2 SMDs were back‐transformed onto a 10‐cm visual analogue scale (VAS) on the basis of a typical pooled standard deviation (SD) of 2.5 cm in large trials that assessed pain using a VAS and expressed as change based on an assumed standardised reduction of 0.72 |SD units in the control group.
3 Percentage of improvement was calculated based on median observed pain at baseline across control groups of large osteoarthritis trials of 6.1 cm on 10‐cm VAS (Nüesch 2009).
4 Absolute response risks for pain in the control groups were assumed 31% (see methods section).
5 SMDs were back‐transformed onto a standardised WOMAC disability score ranging from 0 to 10 on the basis of a typical pooled SD of 2.1 in trials that assessed function using WOMAC disability scores and expressed as change based on an assumed standardised reduction of 0.58 standard deviation units in the control group.
6 Percentage of improvement was calculated based on median observed WOMAC function scores at baseline across control groups of large osteoarthritis trials of 5.6 units (Nüesch 2009).
7 Absolute response risks for function in the control groups were assumed 26% (see methods section).
8 Median control risk across placebo groups in large osteoarthritis trials (see methods section, Nüesch 2009).
9 Downgraded (1 level) because: 9 out of 19 studies reported this outcome, possibly leading to selective outcome reporting bias.
10 Downgraded (2 levels) because: 3 out of 19 studies reported this outcome, possibly leading to selective outcome reporting bias, the CI of the pooled estimate is wide and crossed no difference.
11 Median risk across control groups in included trials.
12 Downgraded (1 level) because 3 out of 22 studies reported this outcome, possible leading to selective outcome reporting bias.

Figuras y tablas -
Summary of findings for the main comparison. Oral or transdermal opioids compared with placebo for osteoarthritis of the knee or hip
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Table 1. Stratified analyses: pain

Variable

Number of
studies

N of participants
opioids

N of participants
control

Pain intensity
SMD (95% CI)

Heterogeneity
I2 (%)

P value*

All trials

22

5180

3095

‐0.28 (‐0.35 to ‐0.20)

58%

Analgesic potency

0.32

Weak

3

79

100

‐0.51 (‐1.01 to ‐0.01)

55%

Strong

19

5101

2995

‐0.26 (‐0.35 to ‐0.18)

64%

Route of administration

0.36

Oral

17

4287

2188

‐0.30 (‐0.41 to ‐0.20)

70%

Transdermal

5

893

907

‐0.20 (‐0.29 to ‐0.11)

0%

Allocation concealment

0.31

Adequate

8

1981

1141

‐0.32 (‐0.44 to ‐0.21)

48%

Inadequate or unclear

14

3199

1954

‐0.24 (‐0.35 to ‐0.13)

67%

Blinding of participants

0.23

Adequate

15

3050

1616

‐0.32 (‐0.42 to ‐0.22)

53%

Inadequate or unclear

7

2130

1479

‐0.21 (‐0.34 to ‐0.08)

73%

Intention‐to‐treat analysis

0.43

Yes

1

283

287

‐0.14 (‐0.30 to 0.02)

N/A

No or unclear

21

4897

2808

‐0.29 (‐0.37 to ‐0.20)

63%

Type of control intervention

0.97

Placebo

20

5132

3030

‐0.28 (‐0.36 to ‐0.19)

65%

No intervention

2

48

65

‐0.33 (‐0.93 to 0.28)

35%

Number of participants randomised

0.08

> 200

16

4895

2796

‐0.24 (‐0.33 to ‐0.16)

64%

≤ 200

6

285

299

‐0.47 (‐0.71 to ‐0.23)

48%

Duration of treatment

0.001

> 1 month

10

2635

1972

‐0.15 (‐0.22 to ‐0.08)

25%

≤ 1 month

12

2545

1123

‐0.40 (‐0.50 to ‐0.30)

37%

Use of analgesic co‐interventions

0.59

Similar between groups

6

1189

891

‐0.31 (‐0.46 to ‐0.16)

60%

Unclear

16

3991

2204

‐0.26 (‐0.36 to ‐0.16)

65%

Type of osteoarthritis

0.77

Hip only

2

48

65

‐0.33 (‐0.93 to 0.28)

35%

Knee only

4

1674

1010

‐0.22 (‐0.41 to ‐0.04)

78%

Knee and hip

16

3458

2020

‐0.29 (‐0.38 to ‐0.20)

56%

*P value for interaction. N/A: not available.
Figuras y tablas -
Table 1. Stratified analyses: pain
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Table 2. Stratified analyses: function

Variable

Number of
studies

N of participants
opioids

N of participants
control

Function
SMD (95% CI)

Heterogeneity
I2 (%)

P value*

All trials

12

2124

1429

‐0.26 (‐0.35 to ‐0.17)

32%

Analgesic potency

0.42

Weak

2

74

95

‐0.42 (‐0.74 to ‐0.10)

6%

Strong

10

2050

1334

‐0.26 (‐0.36 to ‐0.16)

48%

Route of administration

0.76

Oral

9

1679

974

‐0.30 (‐0.43 to ‐0.16)

58%

Transdermal

3

445

455

‐0.25 (‐0.38 to ‐0.12)

0%

Allocation concealment

0.43

Adequate

6

1034

762

‐0.32 (‐0.45 to ‐0.18)

47%

Inadequate or unclear

6

1090

667

‐0.23 (‐0.37 to ‐0.09)

39%

Blinding of participants

0.008

Adequate

10

1656

1038

‐0.32 (‐0.40 to ‐0.24)

0%

Inadequate or unclear

2

468

391

‐0.07 (‐0.20 to 0.07)

0%

Intention‐to‐treat analysis

0.34

Yes

1

171

173

‐0.13 (‐0.34 to 0.08)

N/A

No or unclear

11

1953

1256

‐0.29 (‐0.40 to ‐0.19)

44%

Type of control intervention

0.96

Placebo

11

2081

1369

‐0.28 (‐0.38 to ‐0.18)

49%

No intervention

1

43

60

‐0.29 (‐0.68 to 0.11)

N/A

Number of participants randomised

0.11

> 200

8

1900

1187

‐0.23 (‐0.32 to ‐0.14)

26%

≤ 200

4

224

242

‐0.46 (‐0.73 to ‐0.19)

51%

Duration of treatment

0.41

> 1 month

6

1061

893

‐0.25 (‐0.41 to ‐0.09)

66%

≤ 1 month

6

1063

536

‐0.31 (‐0.42 to ‐0.20)

0%

Use of analgesic co‐interventions

0.38

Similar between groups

4

460

456

‐0.40 (‐0.67 to ‐0.13)

71%

Unclear

8

1664

973

‐0.24 (‐0.33 to ‐0.15)

16%

Type of osteoarthritis

0.45

Hip only

1

43

60

‐0.29 (‐0.68 to 0.11)

N/A

Knee only

2

538

376

‐0.16 (‐0.43 to 0.11)

76%

Knee and hip

9

1543

993

‐0.31 (‐0.41 to ‐0.20)

31%

*P value for interaction. N/A: not available.
Figuras y tablas -
Table 2. Stratified analyses: function
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Comparison 1. Opioids versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain Show forest plot

22

8275

Std. Mean Difference (Random, 95% CI)

‐0.28 [‐0.35, ‐0.20]

1.1 Buprenorphine

4

1401

Std. Mean Difference (Random, 95% CI)

‐0.19 [‐0.30, ‐0.09]

1.2 Codeine

3

179

Std. Mean Difference (Random, 95% CI)

‐0.51 [‐1.01, ‐0.01]

1.3 Fentanyl

1

399

Std. Mean Difference (Random, 95% CI)

‐0.22 [‐0.42, ‐0.03]

1.4 Hydromorphone

1

275

Std. Mean Difference (Random, 95% CI)

0.04 [‐0.19, 0.28]

1.5 Morphine

2

638

Std. Mean Difference (Random, 95% CI)

‐0.25 [‐0.42, ‐0.09]

1.6 Oxycodone

10

2943

Std. Mean Difference (Random, 95% CI)

‐0.31 [‐0.47, ‐0.15]

1.7 Oxymorphone

2

645

Std. Mean Difference (Random, 95% CI)

‐0.39 [‐0.58, ‐0.21]

1.8 Tapentadol

4

1795

Std. Mean Difference (Random, 95% CI)

‐0.31 [‐0.46, ‐0.16]

2 Function Show forest plot

12

3553

Std. Mean Difference (Random, 95% CI)

‐0.26 [‐0.35, ‐0.17]

2.1 Buprenorphine

2

501

Std. Mean Difference (Random, 95% CI)

‐0.23 [‐0.40, ‐0.05]

2.2 Codeine

2

169

Std. Mean Difference (Random, 95% CI)

‐0.42 [‐0.74, ‐0.10]

2.3 Fentanyl

1

399

Std. Mean Difference (Random, 95% CI)

‐0.28 [‐0.48, ‐0.09]

2.4 Morphine

2

639

Std. Mean Difference (Random, 95% CI)

‐0.20 [‐0.38, ‐0.02]

2.5 Oxycodone

4

680

Std. Mean Difference (Random, 95% CI)

‐0.30 [‐0.58, ‐0.01]

2.6 Oxymorphone

2

645

Std. Mean Difference (Random, 95% CI)

‐0.38 [‐0.56, ‐0.19]

2.7 Tapentadol

2

520

Std. Mean Difference (Random, 95% CI)

‐0.15 [‐0.45, 0.16]

3 Number of participants experiencing any adverse event Show forest plot

10

4898

Risk Ratio (IV, Random, 95% CI)

1.49 [1.35, 1.63]

3.1 Buprenorphine

1

199

Risk Ratio (IV, Random, 95% CI)

1.25 [1.09, 1.42]

3.2 Codeine

1

66

Risk Ratio (IV, Random, 95% CI)

1.28 [0.94, 1.75]

3.3 Fentanyl

1

416

Risk Ratio (IV, Random, 95% CI)

1.55 [1.33, 1.81]

3.4 Morphine

1

344

Risk Ratio (IV, Random, 95% CI)

1.10 [0.89, 1.35]

3.5 Oxycodone

6

1779

Risk Ratio (IV, Random, 95% CI)

1.69 [1.47, 1.95]

3.6 Oxymorphone

1

304

Risk Ratio (IV, Random, 95% CI)

1.59 [1.28, 1.97]

3.7 Tapentadol

4

1790

Risk Ratio (IV, Random, 95% CI)

1.39 [1.17, 1.66]

4 Number of participants who withdrew because of adverse events Show forest plot

21

8128

Risk Ratio (IV, Random, 95% CI)

3.76 [2.93, 4.82]

4.1 Buprenorphine

4

1407

Risk Ratio (IV, Random, 95% CI)

3.10 [1.38, 6.94]

4.2 Codeine

3

277

Risk Ratio (IV, Random, 95% CI)

3.67 [2.16, 6.24]

4.3 Fentanyl

1

399

Risk Ratio (IV, Random, 95% CI)

2.63 [1.64, 4.23]

4.4 Hydromorphone

1

288

Risk Ratio (IV, Random, 95% CI)

5.51 [2.54, 11.98]

4.5 Morphine

2

639

Risk Ratio (IV, Random, 95% CI)

2.12 [0.87, 5.15]

4.6 Oxycodone

9

2653

Risk Ratio (IV, Random, 95% CI)

5.55 [3.47, 8.87]

4.7 Oxymorphone

2

674

Risk Ratio (IV, Random, 95% CI)

5.32 [2.93, 9.68]

4.8 Tapentadol

4

1791

Risk Ratio (IV, Random, 95% CI)

2.76 [1.90, 4.00]

5 Number of participants experiencing any serious adverse event Show forest plot

3

681

Risk Ratio (IV, Random, 95% CI)

3.35 [0.83, 13.56]

5.1 Codeine

1

158

Risk Ratio (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Fentanyl

1

416

Risk Ratio (IV, Random, 95% CI)

2.78 [0.57, 13.60]

5.3 Oxycodone

1

107

Risk Ratio (IV, Random, 95% CI)

6.39 [0.34, 120.71]

6 Withdrawal symptoms Show forest plot

3

Odds Ratio (Random, 95% CI)

2.76 [2.02, 3.77]

6.1 Oxycodone

1

Odds Ratio (Random, 95% CI)

2.18 [0.61, 7.81]

6.2 Morphine

1

Odds Ratio (Random, 95% CI)

3.05 [0.12, 75.52]

6.3 Tapentadol

1

Odds Ratio (Random, 95% CI)

0.99 [0.25, 3.97]

6.4 Fentanyl

1

Odds Ratio (Random, 95% CI)

2.97 [2.13, 4.14]
Figuras y tablas -
Comparison 1. Opioids versus placebo
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