| Outcome measure | Study, montelukast effect | Effect | Comment | ||
| ML+ICS effect measure; (SE) or [95% CI] | Sa+ICS effect measure; (SE) or [95% CI] | Difference between groups: Δ; (SE) or [95% CI]; p value | |||
| Symptom score (various scales) | Ilowite 200428 43↓ | −0.48 (0.03*) | −0.66 (0.03*) | Δ = 0.18 [0.10, 0.26] | Change from baseline (improvement = negative changes), mean |
| Nelson 200029 44 45 ↔ | −0.41 (0.03*) | −0.49 (0.04*) | p = 0.199 | ||
| Symptom-free days | Grosclaude 200327↓↓ | 73% | 82% | OR = 1.66 p = 0.005 | Symptom-free days (% of all study days) |
| Ilowite 200428 43↓↓ | 1.15 (0.08*) | 1.69 (0.08*) | Δ = −0.54 [−0.76, −0.32] | Symptom-free days/week; change from baseline (week 0 to 48), mean | |
| Nelson 200029 44 45↓ | 17% | 21% | p = 0.759 | % symptom-free days; change from baseline (week 0 to 12), mean | |
| Ringdal 200330 46 47↓↓ | 39% | 50% | OR = 1.32 [1.05, 1.65] p = 0.017 | % symptom-free days; change from baseline (week 0 to 12), median; OR: symptom-free days during study period | |
| SAM40030 200326 48↓ | 19% | 33% | Δ = 13 [−2, 33] p = 0.064 | % symptom-free days, change from baseline to end of study, median | |
| Symptom-/asthma-free nights | Grosclaude 200327↓↓ | 87% | 93% | OR = 1.96 p = 0.001 | Symptom-free nights (% of all study days) |
| Ringdal 200330 46 47↓↓ | 71% | 79% | OR = 1.28 [1.02, 1.61] p = 0.033 | % symptom-free nights; change from baseline (week 0 to 12), median; OR: symptom-free nights during study period | |
| SAM40030 200326 48↓ | 6% | 13% | Δ = 13 [−2, 35] p = 0.055 | % symptom-free nights, change from baseline to end of study, median | |
| Nocturnal awakenings | Bjermer 200325 42↔ | −1.68 (0.06) | −1.74 (0.06) | Δ = 0.06 [−0.07, 0.20] | Nights with awakenings/week, change from baseline, LS mean |
| Ilowite 200428 43↓↓ | −0.79 (0.05) | −1.02 (0.05) | Δ = 0.23 [0.10, 0.36] | ||
| Exacerbations | Grosclaude 200327↓↓ | 1.54 | 0.96 | Reduction (Sa + ICS) = 38% p = 0.001 | No of exacerbations during 12 week treatment phase, mean |
| Bjermer 200325 42†‡↔ | 150 (20%) | 142 (19%) | RR = 1.02 (0.82, 1.26) | No of patients (%) with ⩾1 exacerbation | |
| Ilowite 200428 43†§↓ | 147 (20%) | 120 (17%) | RR = 1.20 [0.96, 1.49] | ||
| Nelson 200029 44 45↓↓ | 13 (6%) | 4 (2%) | p = 0.031 | ||
| Ringdal 200330 46 47↓↓ | 54 (15%) | 34 (10%) | p<0.05 | ||
| Hospitalisation | Bjermer 200325 42↔ | 5 (<1%) | 7 (<1%) | RR = 0.71 [0.21, 2.22] | Hospitalisation was documented as a component of an exacerbation (Bjermer, Grosclaude, Ilowite, Nelson) or defined as a serious adverse event (Ringdal) |
| Grosclaude 200327↔ | 0 | 0 | – | ||
| Ilowite 200428 43↔ | 3 (<1%) | 5 (<1%) | RR = 0.59 [0.14, 2.45] | ||
| Nelson 200029 44 45↔ | 0 | 0 | – | ||
| Ringdal 200330 46 47↔ | 2 (<1%) | 1 (<1%) | na | ||
| Emergency treatment | Bjermer 200325 42↔ | 21 (3%) | 21 (3%) | RR = 0.99 [0.55, 1.81] | No of patients (%) |
| Ilowite 200428 43↔ | 15 (2%) | 16 (2%) | RR = 0.92 [0.46, 1.84] | ||
| Nelson 200029 44 45↔ | 1 (<1%) | 0 | na | ||
| Additional visits to physician | Bjermer 200325 42↔ | 82 (11%) | 80 (11%) | RR = 1.02 [0.76, 1.36] | No of patients (%) |
| Ilowite 200428 43↓↓ | 107 (15%) | 74 (10%) | RR = 1.41 [1.07, 1.87] | ||
| Nelson 200029 44 45↓ | 9 (4%) | 2 (<1%) | na | ||
| Quality of life | Bjermer 200325 42↔ | 0.71 (0.04) | 0.76 (0.04) | Δ = −0.05 [−0.15, 0.06] p = 0.381 | AQLQ score (7 point scale), change from baseline, mean |
| Ilowite 200428 43 ↓↓ | 0.78 (0.03) | 0.90 (0.03) | Δ = −0.12 [−0.22, −0.02] p = 0.011 | ||
| Satisfaction with treatment | Ringdal 200330 46 47↓↓ | 84% | 93% | p<0.05 | % patients being (very) satisfied (assessed on a 5 point scale) |
| All adverse events | Bjermer 200325 42↔ | 530 (71%) | 538 (72%) | na | No of patients (%) with ⩾1 adverse event |
| Grosclaude 200327↔ | 45 (35%) | 43 (35%) | na | ||
| Ilowite 200428 43↔ | 576 (78%) | 588 (81%) | na | ||
| Nelson 200029 44 45↔ | 119 (53%) | 117 (53%) | na | ||
| Ringdal 200330 46 47↔ | 170 (42%) | 176 (44%) | na | ||
| SAM40030 200326 48↔ | 21 (64%) | 19 (58%) | na | ||
| Serious adverse events | Bjermer 200325 42¶↑↑ | 34 (5%) | 55 (7%) | p = 0.022 | No of patients (%) with ⩾1 serious adverse event |
| Ilowite 200428 43↔ | 22 (3%) | 27 (4%) | na | ||
| Nelson 200029 44 45↔ | 2 (<1%) | 1 (<1%) | na | ||
| Ringdal 200330 46 47↔ | 7 (2%) | 4 (1%) | na | ||
| SAM40030 200326 48↔ | 0 | 2 (6%) | na | ||
| Withdrawals due to adverse events | Bjermer 200325 42↔ | 38 (5%) | 35 (5%) | na | No of patients (%) withdrawn due to adverse events |
| Grosclaude 200327↓ | 5 (4%) | 1 (<1%) | na | ||
| Ilowite 200428 43↑ | 18 (2%) | 31 (4%) | p = 0.06 | ||
| Nelson 200029 44 45↔ | 4 (2%) | 6 (3%) | na | ||
| Ringdal 200330 46 47↔ | 19 (5%) | 13 (4%) | na | ||
| SAM40030 200326 48↔ | 4 (12%) | 2 (6%) | na | ||
↑↑Montelukast better than salmeterol (with statistical significance); ↑montelukast better than salmeterol (without statistical significance); ↔montelukast comparable to salmeterol; ↓montelukast worse than salmeterol (without statistical significance); and ↓↓montelukast worse than salmeterol (with statistical significance).
*Reported as SD in publication; †confirmatory analysis; ‡non-inferiority trial; non-inferiority demonstrated; §non-inferiority trial; non-inferiority not demonstrated; and ¶death of one patient (“death with a severe asthma attack”) in the salmeterol/fluticasone group 15 days after the start of treatment, reported by the investigator as being possibly related to the study drug.
AQLQ, Asthma Quality of Life questionnaire; ICS, inhaled corticosteroids; LS mean, least square mean; ML, montelukast; na, not available; RR, relative risk; Sa, salmeterol; SE, standard error.