Pairwise meta-analysis with grade evidence profile of pharmacological interventions versus placebo for pain
| Intervention | Number of trials (number of participants) | Primary endpoint, weeks | Serious risk of bias?* | Inconsistency | Indirectness | Imprecision | SMD (95% CI)† | Quality of evidence‡ | SMD (95% CI), high risk of bias trials excluded† |
| Capsaicin | 2 (55) | 4 to 9 | Yes | No | No | Yes§¶ | −0.54 (−1.25 to 0.17) | Low | – |
| Topical NSAIDs | 5 (905) | 1 to 6 | Yes | Yes | No | Yes§ | 0.15 (−0.19 to 0.49) | Very low | −0.23 (−0.39 to −0.06) |
| Topical salicylate | 2 (113) | 0.01 to 1 | Yes | No | No | Yes¶ | −0.41 (−0.78 to −0.04) | Low | – |
| Glucosamine | 0 (0) | – | – | – | – | – | – | – | – |
| Galactosaminoglycuronglycan sulfate | 1 (24) | 104 | Yes | No | No | Yes¶ | −0.94 (−1.79 to −0.09) | Low | – |
| Chondroitin sulfate | 3 (162) | 26 to 156 | Yes | No | No | Yes¶ | −0.35 (−0.66 to −0.04) | Low | −0.35 (−0.66 to −0.04) |
| Unsaponifiables | 0 (0) | – | – | – | – | – | – | – | – |
| Paracetamol | 2 (99) | 6 to 24 | Yes | No | No | Yes§¶ | 0.14 (−0.25 to 0.54) | Low | – |
| Per oral NSAIDs | 6 (577) | 2 to 4 | Yes | Yes | No | No | −0.55 (−0.89 to −0.21) | Low | −0.43 (−0.62 to −0.25) |
| Salicylate injection | 1 (40) | 13 | Yes | No | No | Yes§¶ | −0.84 (−1.49 to −0.19) | Low | – |
| Prolotherapy | 1 (25) | 26 | No | No | No | Yes¶ | −0.94 (−1.78 to −0.10) | Moderate | −0.94 (−1.78 to −0.10) |
| Intra-articular platelet-rich plasma | 0 (0) | – | – | – | – | – | – | – | – |
| Intra-articular hyaluronate | 2 (163) | 26 | Yes | No | No | Yes§¶ | 0.08 (−0.23 to 0.39) | Low | −0.11 (−0.75 to 0.53) |
| Intra-articular glucocorticoids | 4 (265) | 12 to 26 | No | Yes | No | Yes§¶ | 0.44 (−0.37 to 1.26) | Low | 0.62 (−0.70 to 1.95) |
| Perineural glucocorticoids | 1 (46) | 4 | Yes (double) | No | Yes** | No | −5.22 (−6.48 to −3.96) | Very low | – |
| Radiation | 1 (55) | 14 | No | No | No | Yes§¶ | −0.10 (−0.63 to 0.43) | Moderate | −0.10 (−0.63 to 0.43) |
| Per oral glucocorticoids | 3 (245) | 4 to 6 | No | Yes | No | Yes§¶ | −0.49 (−0.81 to −0.17) | Low | −0.44 (−0.98 to 0.10) |
| PDE4 inhibitors | 1 (28) | 12 | Yes | No | No | Yes§¶ | −0.44 (−1.24 to 0.37) | Low | – |
| Colchicine | 1 (64) | 12 | No | No | No | Yes¶ | 0.43 (−0.07 to 0.93) | Moderate | – |
| SNRI | 1 (43) | 13 | Yes | No | No | Yes§¶ | −0.48 (−1.09 to 0.13) | Low | – |
| Antiepileptics | 1 (44) | 13 | Yes | No | No | No | −0.81 (−1.43 to −0.19) | Moderate | – |
| Cannabidiol | 1 (74) | 12 | No | No | No | Yes§¶ | 0.10 (−0.35 to 0.56) | Moderate | 0.10 (−0.35 to 0.56) |
| Bisphosphonates | 1 (31) | 26 | Yes (double) | No | No | Yes¶ | −0.62 (−1.39 to 0.15) | Very low | – |
| Hydroxychloroquine | 4 (640) | 24 to 52 | No | No | No | No | 0.01 (−0.15 to 0.16) | High | 0.03 (−0.23 to 0.29) |
| Methotrexate | 1 (64) | 12 | No | No | No | Yes§¶ | −0.36 (−0.85 to 0.14) | Moderate | −0.36 (−0.85 to 0.14) |
| TNF inhibitors | 4 (272) | 6 to 52 | No | Yes | No | Yes§¶ | −0.21 (−0.45 to 0.03) | Low | −0.12 (−0.41 to 0.18) |
| IL-1 inhibitors | 4 (196) | 4 to 16 | Yes | No | Yes†† | Yes¶ | −0.13 (−0.42 to 0.15) | Low | −0.12 (−0.50 to 0.26) |
| IL-6 inhibitor | 1 (83) | 6 | No | No | No | Yes§¶ | 0.10 (−0.33 to 0.53) | Moderate | 0.10 (−0.33 to 0.53) |
| GM-CSF inhibitor | 1 (44) | 6 | No | No | No | Yes¶ | −0.24 (−0.83 to 0.36) | Moderate | −0.24 (−0.83 to 0.36) |
Grade evidence profile of pharmacological interventions for pain. Significant effect estimates are in bold.
*Please see online supplemental file 4 for risk of bias summary.
†Negative values favour interventions; positive values favour comparators.
‡It was not feasible to judge funnel plot asymmetry, because all groups contained <10 trials; no intervention was degraded further because of publication bias.
§95% CI includes appreciable benefit or harm.
¶Small sample size.
**Exercise comparator not an appropriate pharmacological placebo.
††Interventions differ in administration.
.CI, confidence interval; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; NSAID, non-steroidal anti-inflammatory drug; PDE4, phosphodiesterase-4; SMD, standardised mean difference; SNRI, selective norepinephrine reuptake inhibitors; TNF, tumour necrosis factor.