Summary of findings across all outcomes for botulinum toxin type A against a placebo control group or various comparisons. Quality refers to Cochrane Grading of Recommendations Assessment, Development, and Evaluation working group levels of high, moderate, low, or very low.
| Quality Assessment | Summary of Findings | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patients, n | Effect | |||||||||
| Study; Disorder Subtype | Design* Followup Period | Limitations (Risk of Bias)* | Inconsistency* | Indirectness (Generalizability; Group Size)* | Imprecision (Sparse Data; Group Size)* | Int | Cntl | Effect Size (95% CI) or Pooled Effect Size (95% CI) | Clinical Impact, Absolute Benefit, Treatment Advantage, NNT | Quality |
| 1. BoNT-A vs placebo (saline) | ||||||||||
| a. Chronic neck pain — short-term followup | ||||||||||
| Pain | ||||||||||
| Cheshire23; chronic MND (MPS) | AB: BoNT-A 13, Pbo −7 TA 30%, NNT 3 | |||||||||
| Gobel26; chronic MND (MPS, moderate to severe) | RCT-ST | Low | A | A | A | 96 | 93 | SMDp −0.21 (95% CI random −0.50 to 0.07) | AB unknown TA 3% | High |
| Lew28; subacute/chronic MND (MPS) | AB: BoNT-A 2.0, Pbo 1.3 TA 6%, NNT 15 | |||||||||
| Ojala29; chronic MND (MPS) | AB: BoNT-A 1, Pbo 1.2 TA 1% | |||||||||
| Patient global assessment of efficacy | ||||||||||
| Ojala29; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 15 | 16 | SMD −1.12 (95% CI random −1.89 to −0.36) | AB: NA TA 29% | Very low |
| b. Chronic neck pain — intermediate-term followup | ||||||||||
| Pain | ||||||||||
| Lew28; subacute/chronic MND (MPS) | RCT-IT | Low | NA | −1 | −1 | 10 | 14 | SMD −0.56 (95% CI random −1.39 to 0.27) | AB: BoNT-A 2.2, Pbo 0.8 TA 19%, NNT 5 | Low |
| Disability | ||||||||||
| Wheeler36; chronic MND (MPS) | RCT-IT | Low | NA | −1 | −1 | 21 | 24 | SMD 0.43 (95% CI random −0.17 to 1.02) | AB: BoNT-A 14.1, Pbo 15.3 TA −6%, NNT NA | Low |
| Patient global assessment of efficacy | ||||||||||
| Wheeler36; chronic MND (MPS) | RCT-IT | Low | NA | −1 | −1 | 21 | 24 | SMD 0.14 (95% CI random −0.45 to 0.72) | AB, TA, and NNT: NA | Low |
| c. WAD — short-term followup | ||||||||||
| Pain | ||||||||||
| Braker32; WAD subacute | AB: BoNT-A 1.2, Pbo 0.8 TA 7%, NNT 6 | |||||||||
| Carroll33; subacute WAD I and II | RCT-ST | Low | A | A | −1 | 64 | 58 | SMDp −0.21 (95% CI random −0.57 to 0.15) | AB: BoNT-A 2, Pbo 2 TA 0%, NNT 115 | Moderate |
| Freund35; chronic WAD with CGH | AB: BoNT-A 6.2, Pbo −0.8 TA 44%, NNT 3 | |||||||||
| Padberg34; chronic WAD I and II | AB: BoNT-A 12.5, Pbo 5.4 TA 11%, NNT 6 | |||||||||
| Disability | ||||||||||
| Carroll33; subacute WAD I and II | RCT-ST | Low | A | −1 | −1 | 34 | 29 | SMDp 0.15 (95% CI random −0.37 to 0.68) | AB: BoNT-A 6, Pbo 9 TA −6% | Low |
| Freund35; chronic WAD with CGH | AB: BoNT-A 2.9, Pbo 1.7 TA 4% | |||||||||
| Patient global assessment of efficacy | ||||||||||
| Padberg34; chronic WAD I and II | RCT-ST | Low | NA | −1 | −1 | 19 | 20 | Risk ratio 1.05 (95% CI random 0.64 to 1.73) | AB: NA TA − 3% | Low |
| d. WAD — intermediate-term followup | ||||||||||
| Pain | ||||||||||
| Braker32; WAD subacute | RCT-IT | Low | NA | −1 | −1 | 10 | 9 | SMD −0.79 (95% CI random −1.74 to 0.15) | AB: BoNT-A 3.5, Pbo 0.8 TA 45%, NNT 3 | Low |
| Patient global assessment of efficacy | ||||||||||
| Braker32; WAD subacute | RCT-IT | Low | NA | −1 | −1 | 10 | 9 | SMD −0.96 (95% CI random −1.91 to 0.01) | AB: NA TA 20% | Low |
| e. Cervicogenic headache — short-term followup | ||||||||||
| Pain | ||||||||||
| Freund35; chronic WAD with CGH (100%) | RCT-ST | High (−1) | I2 = 56% (−1) | A | −1 | 31 | 27 | SMDp −0.22 (95% CI random −1.02 to 0.58) | AB: BoNT-A 6.2, Pbo −0.8 TA 44%, NNT 3 | Very low |
| Schnider31; chronic MND with CGH | AB: BoNT-A 10, Pbo 10 TA −1%, NNT 264 | |||||||||
| Disability | ||||||||||
| Freund35; chronic WAD with CGH | RCT-ST | Low | NA | −1 | −1 | 14 | 12 | SMD 0.47 (95% CI random −0.31 to 1.26) | AB: BoNT-A 2.9, Pbo 1.7 TA 4% | Low |
| f. Cervicogenic headache — intermediate-term followup | ||||||||||
| Pain | ||||||||||
| Schnider31; chronic MND with CGH | RCT-IT | High (−1) | NA | −1 | −1 | 17 | 15 | SMD 0.00 (95% CI random −0.69 to 0.69) | AB: BoNT-A 11, Pbo 9 TA 3%, NNT 21 | Very low |
| 2. BoNT-A + exercise/medication vs placebo (saline) and exercise/medication* | ||||||||||
| Short-term followup | ||||||||||
| Pain | ||||||||||
| Braker32; subacute WAD | AB: BoNT-A 1.2, Pbo 0.8 TA 7%, NNT 6 | |||||||||
| Ferrante25; chronic MND (MPS) | RCT-ST | Low | A | −2** | −1 | 55 | 59 | SMDp −0.08 (95% CI random −0.45 to 0.29) | AB: BoNT-A 16.8, Pbo 10.4 TA 3%, NNT 15 | Very low |
| Lew28; subacute/chronic MND (MPS) | AB: BoNT-A 2, Pbo 1.3 TA 6%, NNT 15 | |||||||||
| Intermediate-term followup | ||||||||||
| Pain | ||||||||||
| Braker32; subacute WAD | RCT-IT | Low | A | −2** | −1 | 20 | 23 | SMDp −0.66 (95% CI random −1.29 to −0.04) | AB: BoNT-A 3.5, Pbo 0.8 TA 45%, NNT 3 | Very low |
| Lew28; subacute/chronic MPS | AB: BoNT-A 2.2, Pbo 0.8 TA 19% | |||||||||
| 3. BoNT-A + exercise vs exercise at short term | ||||||||||
| Pain | ||||||||||
| Esenyel24; chronic MND (MPS) | Quasi-RCT-ST | High (−1) | NA | −1 | −1 | 18 | 18 | SMD −0.50 (95% CI random −1.16 to 0.17) | AB: NA TA 7% | Very low |
| 4. BoNT-A + exercise vs dry needling plus exercise at short term | ||||||||||
| Pain | ||||||||||
| Kamanli27 vs dry needling; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 9 | 10 | SMD −1.03 (95% CI random −2.01 to −0.06) | AB: BoNT-A 3.4, DNG 1.9 TA 29%, NNT 6 | Very low |
| Disability | ||||||||||
| Kamanli27 vs dry needling; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 9 | 10 | SMD −0.87 (95% CI random −1.82 to 0.09) | AB: BoNT-A 3, DNG 1.7 TA 28% | Very low |
| Quality of life | ||||||||||
| Kamanli27 vs dry needling; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 9 | 10 | SMD −0.63 (95% CI random −1.56 to 0.30) | AB: BoNT-A 6.4, DNG 2 TA 27% | Very low |
| 5. BoNT-A + exercise versus lidocaine plus exercise at short term | ||||||||||
| Pain | ||||||||||
| Esenyel24 vs lidocaine; chronic MND (MPS) | Quasi-RCT or RCT-ST | High (−1) | A | −1 | −1 | 27 | 28 | AB: NA TA −3% | ||
| Kamanli27 vs lidocaine; chronic MND (MPS) | SMDp 0.35 (95% CI random −0.18 to 0.89) | AB: BoNT-A 3.4, LID 5 TA −16% | Very low | |||||||
| Disability | ||||||||||
| Kamanli27 vs lidocaine; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 9 | 10 | SMD 0.21 (95% CI random −0.69 to 1.12) | AB: BoNT-A 3, LID 3.1 TA −7% | Very low |
| Quality of life | ||||||||||
| Kamanli27 vs lidocaine; chronic MND (MPS) | RCT-ST | High (−1) | NA | −1 | −1 | 9 | 10 | SMD 0.71 (95% CI random −0.22 to 1.65) | AB: BoNT-A 6.4, LID 12.1 TA −26% | Very low |
| 6. BoNT-A + exercise vs conventional ultrasound plus exercise at short term | ||||||||||
| Pain | ||||||||||
| Esenyel24 vs conventional US; chronic MND (MPS) | Quasi-RCT-ST | High (−1) | NA | −1 | −1 | 18 | 18 | SMD −0.50 (95% CI random −1.17 to 0.16) | AB: NA TA 8% | Very low |
| 7. BoNT-A + exercise vs pain-threshold ultrasound plus exercise at short term | ||||||||||
| Esenyel24 vs pain-threshold US; chronic MND (MPS) | Quasi-RCT-ST | High (−1) | NA | −1 | −1 | 18 | 18 | SMD −1.41 (95% CI random −2.15 to −0.67) | AB: NA TA 23% | Very low |
↵* Domains that may decrease the quality of the evidence are (1) the study design, (2) risk of bias (quality of evidence), (3) inconsistency of results among studies of the same subgroup, (4) indirectness (nongeneralizability), i.e., the extent to which the people, interventions, and outcome measures are similar to those of interest in the subgroup, and (5) imprecision (insufficient data).
↵** An additional source of bias for the trials on exercise and medication was the lack of standardization and systematic application to all participants. RCT: randomized controlled trial; NA: not applicable or not available; A: adequate; NC: not calculated, data not available; WAD: whiplash-associated disorders; MND: mechanical neck disorder; MPS: myofascial pain syndrome; CGH: cervicogenic headache; Pbo: placebo; BoNT-A: botulinum toxin type A; LID: lidocaine; US: ultrasound; DNG: dry needling group; ST: short term (4 weeks); IT: intermediate term (6 months); I2: Iganen value; SMDp: standard mean difference pooled; RR: relative risk; AB: absolute benefit (difference between end of study mean and baseline mean in the same scale as the outcome concerned); TA: treatment advantage (positive value = advantage to the treatment group, negative value = advantage to the control group, 0% = no difference between the groups, 100% = maximum advantage for the treatment group, −100% = maximum advantage for the control group); NNT: number needed to treat (the number of patients a clinician needs to achieve a clinically important improvement in one); Int: intervention; Cntl: control.