Table 3.
Efficacy results: changes in ESS, CGI, and EQ-5D VAS scores between baseline and 12 months in de novo and exposed patients on monotherapy or receiving various narcolepsy co-medications (intent-to-treat population)
| Endpoint | De novo patients (N = 44) | Exposed patients (N = 24) | Total (N = 68) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Baselinea | Finala | Changea | p-value | n | Baselinea | Finala | Changea | p-value | n | Baselinea | Finala | Changea | |
| ESS (without replacement of missing values) | ||||||||||||||
| Whole population | ||||||||||||||
| ESS score, mean (SE) | 44 | 17.7 ± 0.5 | 12.8 ± 0.7 | −4.9 ± 0.7 | <0.001 | 24 | 15.0 ± 0.6 | 10.8 ± 1.1 | −4.2 ± 1.1 | 0.001 | 68 | 16.8 ± 0.4 | 12.1 ± 0.6 | −4.6 ± 0.6 |
| 95% CI | [16.78; 18.68] | [11.31; 14.37] | [−6.29; −3.49] | [13.71; 16.29] | [8.48; 13.19] | [−6.50; −1.84] | [15.95; 17.58] | [10.85; 13.41] | [−5.82; −3.44] | |||||
| Respondersb, n (%) | 44 | 31 (70.5) | 24 | 13 (54.2) | 68 | 44 (64.7) | ||||||||
| Normalizedb, n (%) | 44 | 12 (27.3) | 24 | 13 (54.2) | 68 | 25 (36.8) | ||||||||
| Concomitant sodium oxybate subgroupc | ||||||||||||||
| ESS score, mean (SE) | 4 | 18.0 ± 2.0 | 16.0 ± 3.1 | −2.0 ± 1.7 | 0.320 | 5 | 15.2 ± 1.3 | 10.0 ± 2.5 | −5.2 ± 2.7 | 0.063 | 9 | 16.4 ± 1.2 | 12.7 ± 2.1 | −3.8 ± 1.7 |
| 95% CI | [11.50; 24.50] | [6.19; 25.81] | [−7.36; 3.36] | [11.43; 18.97] | [2.92; 17.08] | [−12.82; 2.42] | [13.67; 19.22] | [7.77; 17.56] | [−7.69; 0.14] | |||||
| Respondersb, n (%) | 4 | 2 (50.0) | 5 | 3 (60.0) | 9 | 5 (55.6) | ||||||||
| Concomitant psychostimulants only subgroupc | ||||||||||||||
| ESS score | 14 | 17.9 ± 0.9 | 14.2 ± 1.1 | −3.7 ± 0.9 | 0.001 | 4 | 15.5 ± 2.2 | 11.8 ± 4.2 | −3.8 ± 3.1 | 0.312 | 18 | 17.4 ± 0.8 | 13.7± 1.2 | −3.7 ± 0.9 |
| 95%CI | [16.01; 19.84] | [11.71; 16.72] | [−5.64; −1.79] | [8.32; 22.68] | [−1.84; 25.34] | [−13.59; 6.09] | [15.59; 19.19] | [11.02; 16.31] | [−5.67; −1.78] | |||||
| Respondersb, n (%) | 14 | 8 (57.1) | 4 | 2 (50.0) | 18 | 10 (55.6) | ||||||||
| Concomitant anti-cataplectics only subgroupc | ||||||||||||||
| ESS score, mean (SE) | 7 | 18.0 ± 0.9 | 14.4 ± 1.7 | −3.6 ± 1.4 | 0.039 | 4 | 15.8 ± 1.6 | 9.8 ± 3.3 | −6.0 ± 3.4 | 0.175 | 11 | 17.2 ± 0.9 | 12.7 ± 1.6 | −4.5 ± 1.4 |
| 95% CI | [15.61; 20.39] | [10.40; 18.45] | [−6.90; −0.24] | [10.66; 20.84] | [−0.67; 20.17] | [−16.79; 4.79] | [15.24; 19.12] | [9.06; 16.40] | [−7.68; −1.23] | |||||
| Respondersb, n (%) | 7 | 5 (71.4) | 4 | 3 (75.0) | 11 | 8 (72.7) | ||||||||
| Concomitant psychostimulants and anti-cataplecticsc | ||||||||||||||
| ESS score, mean (SE) | 6 | 20.5 ± 0.7 | 15.8 ± 1.2 | −4.7 ± 1.0 | 0.006 | 4 | 12.8 ± 1.4 | 9.3 ± 0.6 | −3.5 ± 1.3 | 0.077 | 10 | 17.4 ± 1.4 | 13.2 ± 1.3 | −4.2 ± 0.8 |
| 95% CI | [18.54; 22.46] | [12.76; 18.90] | [−7.29; −2.04] | [8.18; 17.32] | [7.25; 11.25] | [−7.71; 0.71] | [14.14; 20.66] | [10.26; 16.14] | [−5.98; −2.42] | |||||
| Respondersb, n (%) | 6 | 5 (83.3) | 4 | 3 (75.0) | 10 | 8 (80.0) | ||||||||
| Pitolisant monotherapy | ||||||||||||||
| ESS score, mean (SE) | 17 | 16.5 ± 0.7 | 10.0 ± 1.3 | −6.5 ± 1.4 | <0.001 | 12 | 15.3 ± 0.7 | 11.4 ± 1.6 | −3.9 ± 1.7 | 0.048 | 29 | 16.0 ± 0.5 | 10.6 ± 1.0 | −5.4 ± 1.1 |
| 95% CI | [14.92; 18.02] | [7.26; 12.74] | [−9.57; −3.37] | [13.68; 16.99] | [7.88; 14.95] | [−7.79; −0.04] | [14.91; 17.09] | [8.54; 12.63] | [−7.73; −3.10] | |||||
| Respondersb, n (%) | 17 | 13 (76.5) | 12 | 5 (41.7) | 29 | 18 (62.1) | ||||||||
| ESS (with replacement of missing valuesd) | ||||||||||||||
| ESS score, n (%) | 69 | 17.6 ± 0.3 | 13.6 ± 0.5 | −3.9 ± 0.5 | <0.001 | 29 | 15.1 ± 0.6 | 10.9 ± 0.9 | −4.3 ± 1.0 | <0.001 | 98 | 16.8 ± 0.3 | 12.8 ± 0.5 | −4.0 ± 0.46 |
| 95% CI | [16.82;18.28] | [12.48; 14.76] | [−4.94; −2.91] | [13.98; 16.30] | [8.92; 12.81] | [−6.29; −2.27] | [16.19; 17.48] | [11.81; 13.81] | [−4.94; −3.12] | |||||
| Improvement at CGI of changee (score = 1, 2, or 3) | 44 | 41 (93.2) | 23 | 22 (95.6) | 67 | 63 (94.0) | ||||||||
| EQ-5D VAS, mean (SE) 95% CI |
44 | 62.1 ± 2.4 [57.2; 67.0] |
71.2 ± 2.6 [65.9; 76.5] |
9.1 ± 2.3 [4.5; 13.7] |
<0.001 | 24 | 71.8 ± 3.0 [65.6; 78.0] |
74.5 ± 2.9 [68.4; 80.5] |
2.7 ± 3.1 [−3.7; 9.0] |
0.395 | 68 | 65.5 ± 1.9 [61.6; 69.4] |
72.4 ± 2.0 [68.4; 76.3] |
6.8 ± 1.8 [3.1; 10.6] |
ESS = Epworth Sleepiness Scale; CGI of change = Clinical Global Impression of change; EQ-5D = European Quality of life questionnaire (100 corresponds to the best health and 0 to the worst). Significant p-values are bolded.
aBaseline, final, change: mean ± SD or n (%); Change: Change from Baseline.
bResponders were defined as patients with ESSB – ESSF ≥ 3; Normalized patients were patients with ESSF ≤ 10.
cSubgroup of patients with concomitant sodium oxybate = patients who received sodium oxybate at least once in addition to pitolisant; Subgroup of patients with concomitant psychostimulants = patients who received modafinil, methylphenidate, or mazindol in addition to pitolisant, but no other concomitant anti-cataplectic agent, during the study; Subgroup of patients with concomitant anti-cataplectic agents = patients who received sodium oxybate, SSRIs, or clomipramine in addition to pitolisant, but no other concomitant psychostimulant, during the study; Subgroup of patients with concomitant psychostimulants and anti-cataplectics = patients who received both concomitant psychostimulants and anti-cataplectic agents in addition to pitolisant during the study; Subgroup of patients with concomitant SSRIs = patients who received SSRIs for narcolepsy, in addition to pitolisant, but no other treatment for narcolepsy; Subgroup of patients with cataplexy and concomitant SSRIs = patients who had history of cataplexy at baseline and took concomitant SSRIs at least once during the study.