Table 4 Pain outcomes of MAO-BI studies.
Studies | Study design | Participants | Study quality | Age | Disease duration | Instruments | Outcome | Effect size |
|---|---|---|---|---|---|---|---|---|
Hattori et al. (2018)31 | Multicenter, double-blind, placebo-controlled RCT, 26 weeks | 404 patients, advanced PD with off time ≥ 2.5 hours | 1 | 66.1 (8.3) | 9.0 (4.7) | PDQ-39: bodily discomfort | Significantly better in rasagiline 1 mg vs placebo, −4.28 (−8.20 to −0.36), p = 0.0326 | IC |
PDQ-39: bodily discomfort | No significant difference between rasagiline 0.5 mg and placebo, 1.00 (−4.85 to 2.85), p = 0.6099 | IC | ||||||
Zang et al. (2018)32 | Multicenter, double-blind, placebo-controlled RCT, 16 weeks | 324 patients, advanced PD with off time ≥ 1 hour | 1 | 62.2 (9.4) | 7.3 (4.6) | PDQ-39: bodily discomfort | Significantly better in rasagiline 1 mg vs placebo, −3.9 (−7.65 to −0.12), p = 0.043 | IC |
Hattori et al. (2019)29 | Multicenter, double-blind, placebo-controlled RCT, 26 weeks | 244 early PD patients not taking antiparkinsonian medication | 1 | 66.4 (8.9) | 1.8 (1.6) | PDQ-39: bodily discomfort | No significant differences between rasagiline 1 mg and placebo, −0.47 (−4.28 to 3.35), P = 0.8093 | IC |
Zhang et al. (2018)30 | Multicenter, double-blind, placebo-controlled RCT, 26 weeks | 130 early PD patients not taking antiparkinsonian medication | 1 | 59.0 (8.9) | 0.1 (median) | PDQ-39: bodily discomfort | No significant differences between groups; rasagiline 1 mg 2.14 ± 2.01 vs. placebo 1.28 ± 2.05, P = 0.749 | IC |
Barone et al. (2015)17 | Multicenter, double-blind, placebo-controlled RCT, 12 weeks | 123 patients, PD with moderate depression (BDI ≥ 15) | 1 | 66.1 (8.5) | 4.3 (12.5) | PDQ-39: bodily discomfort | No significant difference between groups, rasagiline 1 mg 2.01 ± 2.97 vs. placebo 2.72 ± 2.65, P value not shown | 0.09 |
Hattori et al. (2019)36 | Multicenter, open-label, prospective, phase 3 study, 52 weeks | 222 PD patients taking levodopa with or without motor fluctuation | 3 | 68.0 (8.4) | 7.1 (5.0) | PDQ-39: bodily discomfort | No significant change with rasagiline 1 mg; baseline to post −1.29 ± 19.45, P value not shown | IC |
Cibulcik et al. (2016)21 | Single-center, open-label, prospective study, 3 months | 42 patients, PD with freezing of gait | 3 | 69.5 (7.9) | 8.3 (4.3) | PDQ-39: bodily discomfort | Significant improvement with rasagiline 1 mg; baseline 27.5 ± 17.3 and post 23.4 ± 18.9, p = 0.039 | 0.24 |
Cattaneo et al. (2017)108 | Post-hoc analysis of two multicenter, double-blind, placebo-controlled RCTs, 6 months | 995 patients, advanced PD with off time > 1.5 h | 1 | 60.9 (9.2) | 8.6 (4.2) | PDQ-39 bodily discomfort | Significantly better in safinamide; safinamide 100 mg −5.28 ± 1.49 vs. placebo −1.59 ± 1.50, P = 0.0007 | 0.23 |
Borgohain et al. (2014)37 | Multicenter, double-blind, placebo-controlled RCT, 24 weeks | 669 patients, advanced PD with off time > 1.5 h | 1 | 59.9 (9.4) | 8.1 (3.9) | PDQ-39: bodily discomfort | Significantly better in safinamide; safinamide 100 mg −3.5 vs. placebo 0.2, P = 0.0159 | 0.16 |
PDQ-39: bodily discomfort | No significant differences between groups; safinamide 50 mg −1.3 vs. placebo 0.2, P = 0.4937 | 0.06 | ||||||
Tsuboi et al. (2021)59 | Multicenter, double-blind, placebo-controlled RCT, 24 weeks | 406 patients, advanced PD with wearing off | 1 | 68.1 (8.6) | 8.2 (4.9) | PDQ-39: bodily discomfort | No significant differences between groups; safinamide 50 mg −1.71 ± 1.44 vs. placebo −2.94 ± 1.41, P = 0.5407 | 0.07 |
PDQ-39: bodily discomfort | No significant differences between groups; safinamide 100 mg −6.13 ± 1.45 vs. placebo −2.94 ± 1.41, P = 0.118 | 0.28 | ||||||
Cattaneo et al. (2018)60 | Post-hoc analysis of a multicenter, double-blind, placebo-controlled RCT, 2 years | 355 patients, advanced PD with off time > 1.5 h | 1 | NA | NA | PDQ-39 bodily discomfort | Significantly better in safinamide 100 mg vs placebo, −3.66 (−6.71 to −0.60), P = 0.0190 | IC |
Santos García et al. (2021)25 | Multicenter, open-label, prospective study, 6 months | 50 patients, PD with high non-motor burden (NMSS ≥ 40) | 3 | 68.5 (9.1) | 6.4 (5.1) | King’s PD pain scale | Significant improvement with safinamide 100 mg; baseline 40.0 ± 36.2 and post 22.6 ± 21.4, P < 0.0001 | 0.48 |
Visual Analog Scale: pain | No significant change with safinamide 100 mg; baseline 4.6 ± 3.2 and post 3.7 ± 2.7, P = 0.071 | 0.29 | ||||||
PDQ-39: bodily discomfort | Significant improvement with safinamide 100 mg; baseline 44.6 ± 27.4 and post 33.3 ± 19.9, P = 0.018 | 0.41 | ||||||
Grigoriou et al. (2021)43 | Multicenter, open-label, prospective study, 6 months | 27 patients, advanced PD with off time > 1.5 ho | 3 | 65 | 6.8 | King’s PD pain scale | Significant improvement with safinamide 100 mg; mean score, baseline 18.0 and post 12.4, P = 0.02 | IC |
De Micco et al. (2021)44 | Single-center, open-label, prospective study, 6 months | 20 patients, advanced PD with off time > 1.5 h | 3 | 63.8 (10.2) | 6.0 (2.2) | King’s PD Pain Scale | No significant change with safinamide 50 mg; baseline 9.40 ± 7.88 and post 8.60 ± 9.20, P = 0.77 | 0.10 |
Geroin et al. (2020)46 | Single-center, open-label, prospective study, 12 weeks | 13 patients, advanced PD with motor fluctuation and pain (NRS ≥ 4) | 3 | 64.1 (6.7) | 5.8 (2.9) | King’s PD pain scale | Significant improvement with safinamide 100 mg; baseline to post −19.3 ± 10.5, P < 0.05 | IC |
Brief Pain Inventory: Intensity | Significant improvement with safinamide 100 mg; baseline to post −11.8 ± 5.2, P < 0.05 | IC | ||||||
Brief Pain Inventory: Interference | Significant improvement with safinamide 100 mg; baseline to post −24.4 ± 11.1, P < 0.05 | IC | ||||||
NRS | Significant improvement with safinamide 100 mg; baseline to post −4.6 ± 1.9, P < 0.05 | IC | ||||||
PDQ-39 bodily discomfort | Significant improvement with safinamide 100 mg; baseline to post −4.5 ± 2.4, P < 0.05 | IC |
