Inhibidores de la interleucina 13 y la interleucina 4 versus placebo, inhibidores de la interleucina 5 o sustancias antiinmunoglobulina E para personas con asma
Appendices
Appendix 1. Sources and search methods for the Cochrane Airways Trials Register (CAGR)
Electronic searches: core databases
| Database | Dates searched | Frequency of search |
| CENTRAL (via the Cochrane Register of Studies (CRS)) | From inception | Monthly |
| MEDLINE (Ovid) | 1946 onwards | Weekly |
| Embase (Ovid) | 1974 onwards | Weekly |
| PsycINFO (Ovid) | 1967 onwards | Monthly |
| CINAHL (EBSCO) | 1937 onwards | Monthly |
| AMED (EBSCO) | From inception | Monthly |
Handsearches: core respiratory conference abstracts
| Conference | Years searched |
| American Academy of Allergy, Asthma and Immunology (AAAAI) | 2001 onwards |
| American Thoracic Society (ATS) | 2001 onwards |
| Asia Pacific Society of Respirology (APSR) | 2004 onwards |
| British Thoracic Society Winter Meeting (BTS) | 2000 onwards |
| Chest Meeting | 2003 onwards |
| European Respiratory Society (ERS) | 1992, 1994, 2000 onwards |
| International Primary Care Respiratory Group Congress (IPCRG) | 2002 onwards |
| Thoracic Society of Australia and New Zealand (TSANZ) | 1999 onwards |
Asthma search
1. exp Asthma/
2. asthma$.mp.
3. (antiasthma$ or anti‐asthma$).mp.
4. Respiratory Sounds/
5. wheez$.mp.
6. Bronchial Spasm/
7. bronchospas$.mp.
8. (bronch$ adj3 spasm$).mp.
9. bronchoconstrict$.mp.
10. exp Bronchoconstriction/
11. (bronch$ adj3 constrict$).mp.
12. Bronchial Hyperreactivity/
13. Respiratory Hypersensitivity/
14. ((bronchial$ or respiratory or airway$ or lung$) adj3 (hypersensitiv$ or hyperreactiv$ or allerg$ or insufficiency)).mp.
15. ((dust or mite$) adj3 (allerg$ or hypersensitiv$)).mp.
16. or/1‐15
Filter to identify RCTs
1. exp "clinical trial [publication type]"/
2. (randomized or randomised).ab,ti.
3. placebo.ab,ti.
4. dt.fs.
5. randomly.ab,ti.
6. trial.ab,ti.
7. groups.ab,ti.
8. or/1‐7
9. Animals/
10. Humans/
11. 9 not (9 and 10)
12. 8 not 11
The MEDLINE strategy and RCT filter are adapted to identify trials in other electronic databases.
Appendix 2. Search strategy to identify relevant studies from the Cochrane Airways Trials Register
1. AST:MISC1
2. MeSH DESCRIPTOR Asthma Explode All
3. asthma*:ti,ab
4. #1 or #2 or #3
5. Lebrikizumab:TI,AB,KW
6. MILR1444A
7. GSK679586
8. Tralokinumab:TI,AB,KW
9. CAT‐354
10. Anrukinzumab:TI,AB,KW
11. IMA‐638
12. IMA‐026
13. Pascolizumab:ti,ab,kw
14. SB 240683
15. Altrakincept:ti,ab,kw
16. AMG‐317
17. Dupilumab:ti,ab,kw
18. REGN668
19. pitrakinra:ti,ab,kw
20. aerovant:ti,ab,kw
21. AER 001
22. IL‐13:ti,ab,kw
23.anti‐IL‐13:ti,ab,kw
24. Interleukin 13:ti,ab,kw
25. anti‐Interleukin‐13:ti,ab,kw
26. IL‐4:ti,ab,kw
27. anti‐IL‐4:ti,ab,kw
28. Interleukin 4:ti,ab,kw
29. anti‐interleukin‐4:ti,ab,kw
30. #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29
31. #30 AND #4
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Forest plot of comparison: 1 Anti‐interleukin‐13 or ‐4 agents with placebo, outcome: 1.1 Exacerbation requiring hospitalisation or ED visit.
Forest plot of comparison: 1 Anti‐interleukin‐13 or ‐4 agents with placebo, outcome: 1.2 Health‐related quality of life (adjusted mean diff versus placebo). A change of 0.5 is considered the minimum clinically significant difference (MCID).
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 3: Serious adverse events
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 4: Exacerbation requiring OCS (rate ratio)
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 5: Exacerbation requiring OCS (dichotomous)
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 6: Change from baseline in pre‐bronchodilator FEV1
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 7: Change from baseline in ACQ score
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 8: Adverse events
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 9: Change from baseline in FENO, ppb
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 10: Change from baseline in blood eosinophils, cells x 10*9/L
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 11: Change from baseline in periostin, ng/mL
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 12: Percentage reduction from baseline in OCS use
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 13: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 1: Anti‐interleukin‐13 or ‐4 agents with placebo, Outcome 14: Exacerbation requiring hospitalisation/ED/OCS (relative risk)
Comparison 2: Subanalysis: agents directly targeting IL‐13, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 2: Subanalysis: agents directly targeting IL‐13, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 2: Subanalysis: agents directly targeting IL‐13, Outcome 3: Serious adverse events
Comparison 2: Subanalysis: agents directly targeting IL‐13, Outcome 4: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 3: Subanalysis: agents directly targeting IL‐4R, Outcome 1: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 3: Subanalysis: agents directly targeting IL‐4R, Outcome 2: Serious adverse events
Comparison 3: Subanalysis: agents directly targeting IL‐4R, Outcome 3: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 4: Subanalysis: study duration <= 6 months, Outcome 1: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 4: Subanalysis: study duration <= 6 months, Outcome 2: Serious adverse events
Comparison 4: Subanalysis: study duration <= 6 months, Outcome 3: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 5: Subanalysis: study duration > 6 months, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 5: Subanalysis: study duration > 6 months, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 5: Subanalysis: study duration > 6 months, Outcome 3: Serious adverse events
Comparison 5: Subanalysis: study duration > 6 months, Outcome 4: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 6: Subanalysis: asthma severity mild‐to‐moderate, Outcome 1: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 6: Subanalysis: asthma severity mild‐to‐moderate, Outcome 2: Serious adverse events
Comparison 7: Subanalysis: asthma severity severe, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 7: Subanalysis: asthma severity severe, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 7: Subanalysis: asthma severity severe, Outcome 3: Serious adverse events
Comparison 7: Subanalysis: asthma severity severe, Outcome 4: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 8: Subanalysis: no concomitant ICS, Outcome 1: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 8: Subanalysis: no concomitant ICS, Outcome 2: Serious adverse events
Comparison 9: Subanalysis: concomitant ICS, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 9: Subanalysis: concomitant ICS, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 9: Subanalysis: concomitant ICS, Outcome 3: Serious adverse events
Comparison 9: Subanalysis: concomitant ICS, Outcome 4: Exacerbation requiring hospitalisation/ED/OCS (rate ratio)
Comparison 10: Subanalysis by blood eosinophil count: exacerbations requiring hospitalisation/ED/OCS, Outcome 1: Blood eosinophils high (> 300 cells/uL)
Comparison 10: Subanalysis by blood eosinophil count: exacerbations requiring hospitalisation/ED/OCS, Outcome 2: Blood eosinophils low (< 300 cells/uL)
Comparison 10: Subanalysis by blood eosinophil count: exacerbations requiring hospitalisation/ED/OCS, Outcome 3: Blood eosinophils low (> 150 < 300 cells/uL)
Comparison 10: Subanalysis by blood eosinophil count: exacerbations requiring hospitalisation/ED/OCS, Outcome 4: Blood eosinophils low (< 150 cells/uL)
Comparison 11: Subanalysis by FENO: exacerbations requiring hospitalisation/ED/OCS, Outcome 1: FENO high (≥ 50 ppb)
Comparison 11: Subanalysis by FENO: exacerbations requiring hospitalisation/ED/OCS, Outcome 2: FENO medium (≥ 25 to < 50 ppb)
Comparison 11: Subanalysis by FENO: exacerbations requiring hospitalisation/ED/OCS, Outcome 3: FENO low (< 25 ppb)
Comparison 12: Subanalysis by periostin level: exacerbations requiring hospitalisation/ED/OCS, Outcome 1: Periostin high (≥ 50 ng/mL)
Comparison 12: Subanalysis by periostin level: exacerbations requiring hospitalisation/ED/OCS, Outcome 2: Periostin low (< 50 ng/mL)
Comparison 13: Sensitvity analysis ‐ random‐effects, Outcome 1: Exacerbation requiring hospitalisation or ED visit
Comparison 13: Sensitvity analysis ‐ random‐effects, Outcome 2: Health‐related quality of life (adjusted mean diff versus placebo)
Comparison 13: Sensitvity analysis ‐ random‐effects, Outcome 3: Serious adverse events
| Anti‐IL13 of anti‐IL4 agents compared to placebo for children and adults with asthma | ||||||
| Patient or population: children and adults with asthma | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with anti‐IL13 of anti‐IL4 agents | |||||
| Exacerbation requiring hospitalisation or ED visit Follow‐up: 52 weeks | The mean AAER in the placebo group was 0.0751 | The AAER in the intervention group was 0.024 lower (0.002 lower to 0.04 lower) | Rate ratio 0.68 | 2039 | ⊕⊕⊕⊝ | |
| Health‐related quality of life (AQLQ) Scale: 1 to 7 (higher is better) Follow‐up: 12 weeks to 52 weeks | Where reported, the mean change in the placebo group ranged from 0.64 to 0.88 | MD 0.18 higher | ‐ | 4960 | ⊕⊕⊕⊕ | MCID = 0.5; the treatment effect was not clinically relevant. |
| Serious adverse events Follow‐up: 3 to 52 weeks | 81 per 1000 | 74 per 1000 | OR 0.91 | 7739 | ⊕⊕⊕⊝ | |
| Exacerbation requiring OCS (rate ratio) Follow‐up: 52 weeks | The mean AAER in the placebo group was 0.90 | The AAER in the intervention group was 0.08 lower (0.27 lower to 0.29 higher) | RR 0.98 | 452 | ⊕⊕⊝⊝ | |
| Change from baseline in ACQ score Scale: 0 to 6 (higher is worse) Follow‐up: 12 to 52 weeks | Where reported, the mean change from baseline in ACQ score in the placebo group ranged from ‐1.30 (SE 0.06) to ‐0.27 (error NR) | MD 0.19 lower | ‐ | 6251 | ⊕⊕⊕⊝ | MCID = 0.4; the treatment effect was not clinically relevant. |
| Adverse events (any) Follow‐up: 10 days to 52 weeks | 707 per 1000 | 737 per 1000 | OR 1.16 | 7419 | ⊕⊕⊕⊕ | |
| Time off work or study | ‐ | ‐ | ‐ | ‐ | ‐ | No studies reported data for this outcome. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Mean of the AAER in the placebo group of the two studies: 0.07 and 0.08 2Downgraded once for indirectness (low number of studies of a single agent) 3Downgraded once for imprecision as the 95% confidence intervals for the treatment effect crossed 1.0 4 Downgraded once for inconsistency (moderate heterogeneity of 30% to 60%) 6Downgraded twice for inconsistency (substantial heterogeneity of 50% to 90% or considerable heterogeneity of 75% to 100%) | ||||||
| Anti‐IL13 of anti‐IL4 agents compared to placebo for children and adults with asthma | ||||||
| Patient or population: children and adults with asthma | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with anti‐IL13 of anti‐IL4 agents | |||||
| Change from baseline in pre‐bronchodilator FEV1 Follow‐up: 12 to 52 weeks | Where reported, the mean change from baseline in FEV1 in the placebo groups ranged from ‐0.02 L (SE 0.03) to 0.21 L (SE 0.02) | MD 0.1 L higher | ‐ | 4829 | ⊕⊕⊕⊝ | These changes were borderline clinically relevant (MCID is approximately 0.1 to 0.2 L). |
| Change from baseline in FENO (ppb) Follow‐up: 10 days to 52 weeks | Where reported, the mean change from baseline in FENO in the placebo groups ranged from ‐31.1 to 23.8 ppb | MD 14.68 ppb lower | ‐ | 3577 | ⊕⊕⊕⊝ | |
| Change from baseline in blood eosinophils (cells x 10*9/L) Follow‐up: 12 to 52 weeks | Where reported, the mean change from baseline in blood eosinophil count in the placebo groups ranged from ‐0.048 (SD 0.347) to 0.003 (SD 0.313) cells x 109/L | MD 0.06 cells x 10*9/L higher | ‐ | 2598 | ⊕⊕⊕⊕ | |
| Change from baseline in Periostin (ng/mL) Follow‐up: 12 to 52 weeks | Where reported, the mean change from baseline in periostin concentration in the placebo groups ranged from ‐5.05 (SD 27.89) to ‐0.3 (SD 1.0) ng/mL | MD 9.04 ng/mL lower | ‐ | 2106 | ⊕⊕⊝⊝ | |
| Percentage reduction from baseline in maintenance OCS dose Follow‐up: 24 to 40 weeks | Where reported, the mean reduction from baseline in OCS dose in the placebo groups ranged from ‐29.85 (SE 4.98) to ‐41.9 (SE 4.6)% | MD 15.58% lower | ‐ | 350 | ⊕⊕⊝⊝ | |
| Post hoc exploratory endpoint: Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Follow‐up: 24 weeks to 52 weeks | The mean AAER in the placebo groups was 1.00 (range 0.60 to 2.31)1 | The AAER in the intervention groups was 0.29 lower (0.35 lower to 0.23 lower) | Rate ratio 0.71 | 6998 | ⊕⊕⊝⊝ | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Mean of the AAER in the placebo groups of the seven studies (1 study had two placebo arms): 2.31, 0.60, 0.82, 0.94, 0.61, 0.87, 0.97, 0.897 2 Downgraded once for inconsistency (moderate heterogeneity of 30% to 60%) 3Downgraded twice for inconsistency (substantial heterogeneity of 50% to 90% or considerable heterogeneity of 75% to 100%) | ||||||
| Study | Intervention | Treatment duration (weeksc) | Asthma severity | ICS use | N randomised | Age range, years | Range % male | BL % pred. FEV1 |
| IL‐4R 500/1500 μg single dose | 2 | Moderate atopic | Discontinued prior to study drug | 25 (17/8) | 35 to 38 | 25 to 63 | 7 to 87 | |
| IL‐4R 0.75/1.5/3.0 mg Q1W | 12 | Moderate‐to‐severe | Discontinued prior to study drug | 62 (46/16) | 36 to 46 | 25 to 37 | 75 to76 | |
| (NCT01402986) | Tralokinumab 300 mg Q2W or Q4W | 52 | Severe uncontrolled | Maintained through study | 452 (376/76) | 50 to 51 | 33 to 36 | 68 to 69 |
| (NCT02473939) | VR492 0.5/10/20 mg as DPI | 28 | Mild | Maintained through study | 45 (29/16) | 29 to 30 | 100 | 77 to 89 |
| (NCT02281357) | Tralokinumab 300 mg Q2W | 40 | Severe | Maintained through study | 140 (70/70) | 54 to 55 | 32 to 44 | NR |
| (NCT02414854) | Dupilumab 200/300 mg SC Q2W | 52 | Severe uncontrolled | ICS permitted (≥ 500 μg FP or equiv.) | 1902 (1264/638) | 48 | 37 | 58 |
| (NCT 00436670) | Tralokinumab 75/150/300 mg Q1W | 12 | Moderate‐to‐severe | Stable doses of ICS (200 to 1000 μg FP or equiv.) | 294 (220/74) | 40 to 43 | 38 to 46 | 67 to 70 |
| (NCT00930163) | Lebrikizumab 250 mg SC Q4W | 24 | Moderate‐to‐severe uncontrolled | ICS maintained throughout study | 218 (106/112) | 44 to 45 | 33 to 35 | 64 to 66 |
| (NCT00843193) | GSK679586 10 mg/kg IV Q4W | 12 | Severe refractory | Max recommended ICS doses maintained | 198 (99/99) | 51 | 48 to 51 | 55 to 58 |
| (NCT00410280) | IMA‐638 4 mg/kg (2 doses, 1 week apart) | AC study (2) | Mild, allergic asthma | Not permitted | 27 (14/13) | 26 to 32 | 38 to 50 | 87 to 93 |
| (NCT00725582) | IMA‐638 4 mg/kg (2 doses, 1 week apart) | AC study (2 ) | Mild, allergic asthma | Not permitted | 29 (14/15) | 33 to 34 | 50 to 53 | 87 to 91 |
| Lebrikizumab (dose not stated) | 24 | Uncontrolled by ICS | Maintained throughout study | 180 (88/92) | NR | NR | NR | |
| (NCT01545440) | Lebrikizumab 37.5/125/250 mg SC Q4W | 52a | Moderate‐to‐severe uncontrolled | SOC maintained (500 to 2000 μg/day FPA or equiv.) | 463 (347/116) | 47 to 50 | 39 to 57 | 61 to 63 |
| (NCT01545453) | Lebrikizumab 37.5/125/250 mg SC Q4W | 52a | Moderate‐to‐severe uncontrolled | SOC maintained (500 to 2000 μg/day FPA or equiv.) | See Hanania 2015aa | |||
| (NCT01867125) | Lebrikizumab 37.5/125 mg SC Q4W | 52 | Moderate‐to‐severe | SOC maintained (500 to 2000 μg/day FPA or equiv.) | 1081 (719/362) | 51 | 31 to 36 | 61 |
| (NCT01868061) | Lebrikizumab 37.5/125 mg SC Q4W | 52 | Moderate‐to‐severe | SOC maintained (500 to 2000 μg/day FPA or equiv.) | 1067 (713/354) | 50 to 51 | 34 to 43 | 61 |
| (NCT00411814) | GSK679586 2.5/10/20 mg/kg Q4W | 12 | Mild bronchial | Not permitted | 28 (21/7) | 25 to 32 | 100 | 102 to 105 |
| (NCT02104674) | Lebrikizumab 125 mg SC Q4W | 12 | Mild‐to‐moderate | Discontinued 30 days prior to study drug | 211 (105/106) | 43 to 45 | 37 to 39 | 72 |
| IMA‐638 0.2/0.6/2/ mg/kg SC D1/8/28/56/70/84 | 16 | Moderate‐to‐severe persistent | Medium‐to‐high dose permitted | 159 (98/61) | NR | 39 to 45 | NR | |
| Tralokinumab 1/5/10 mg/kg Q4W | 12 | Uncontrolled refractory | Maintained (≥ 800 μg BDP or equiv.) | 14 (11/3) | 34 to 41 | 0 to 75 | NR | |
| (NCT00971035) | Lebrikizumab 125/250/500 mg SC Q4W | 12 | Stable, mild‐to‐moderate | Not permitted | 212 (160/52) | 38 to 41 | 32 to 43 | 72 to 4 |
| Pannetieri 2018A (NCT02161757) | Tralokinumab 300 mg SC Q2W or Q4W | 52 | Severe uncontrolled | Stable dose (≥ 500 μg FP or equiv.) | 1207 (807/400) | 49 to 51 | 30 to 37 | 60 to 62 |
| (NCT02194699) | Tralokinumab 300 mg SC Q2W | 52 | Severe uncontrolled | Stable dose (≥ 500 μg FP or equiv.) | 856 (428/428) | 47 to 48 | 31 to 34 | 61 |
| (NCT00873860) | Tralokinumab 150/300/600 mg SC Q2W | 12 | Moderate‐to‐severe uncontrolled | Permitted | 194 (146/48) | 43 to 50 | 29 to 60 | NR |
| (NCT02528214) | Dupilumab 300 mg SC Q2W | 24 | Severe asthma | Tapered down | 210 (103/107) | 51 to 52 | 39 to 40 | NR |
| (NCT02449473) | Tralokinumab 300 mg SC Q2W | 12 | Moderate‐to‐severe uncontrolled | Stable dose (≥ 250 μg FP daily or equiv.) | 79 (39/40) | 47 to 50 | 41 to 50 | NR |
| (NCT00781443) | Lebrikizumab 5 mg/kg SC Q4W | AC study (12) | Mild | Not stated | 29 (13/16) | 32 to 66 | 46 to 56 | 82‐84 |
| (NCT00974675) | Tralokinumab 1/5/10 mg/kg IV Q4W | 21 | Mild well‐controlled | Permitted | 23 (19/4) | 35 to 43 | 67 to 100 | NR |
| (NCT00986037) | RPC4046 0.3/3 mg/kg IV Q1W | 16 | Mild‐to‐moderate controlled | Low‐to‐medium dose permitted | 27 (20/7) | 23 to 33 | 75 to 100 | NR |
| (NCT00535028) | Pitrakinra 25 mg SC once daily for 28 days | AC study (28 days) | Mild‐to‐moderate | Discontinued 1 month prior to study drug | 24 (12/12) | 30 to 31 | 42 to 58 | 100‐102 |
| (NCT00535031) | Pitrakinra 60 mg nebulised twice daily for 28 days | AC study (28 days) | Mild‐to‐moderate | Discontinued 1 month prior to study drug | 32 (16/16) | 25 to 29 | 47 to 80 | 96 to ‐99 |
| (NCT00801853) | Pitrakinra 1/3/10 mg | 12 | Moderate‐to‐severe uncontrolled | Fluticasone withdrawal from 6 weeks after initiation of blinded treatment | 534 (397/137) | NR | NR | NR |
| (NCT01312961) | Dupilumab 300 mg SC Q1W | 12 | Moderate‐to‐severe | Medium‐to‐high dose discontinued during weeks 6 to 9 | 104 (52/52) | 38 to 42 | 50 | 72 |
| (NCT01854047) | Dupilumab 200/300 mg SC Q2/4W | 24 | Uncontrolled persistent asthma | Medium‐to‐high dose plus LABA | 619 (461/158) | 48 to 51 | 34 to 44 | 60 to 61 |
| aThis trial was designed to be 52 weeks; however, the trial was terminated early and the median duration of treatment was approximately 24 weeks. Pooled data are reported for the two replicate studies. bPhase 1 safety and PK study cUnless otherwise stated Abbreviations: AC: allergen challenge; BDP: beclomethasone dipropionate; DPI: dry powder inhaler; FEV1: forced expiratory volume in one second; FP: fluticasone propionate; ICS: inhaled corticosteroids; IL‐4R: interleukin‐4 receptor; IL‐13: interleukin‐13; IV: intravenous; LABA: long‐acting beta‐agonist; NR: not reported; PK: pharmacokinetic; Q1/2/4W: every 1/2/4 weeks; SC: subcutaneous; SOC: standard of care. | ||||||||
| Outcome | Fixed‐effect model | Random‐effects model |
| Exacerbation requiring hospitalisation or ED visit | RR 0.68, 95% CI 0.47 to 0.98 (participants = 2039; studies = 2) | RR 0.68, 95% CI 0.47 to 0.98 |
| HRQoL (AQLQ) | MD 0.18, 95% CI 0.12 to 0.24 (participants = 4960; studies = 7) | MD 0.18, 95% CI 0.12 to 0.24 |
| Serious adverse events | OR 0.91, 95% CI 0.76 to 1.09 (participants = 7739; studies = 22) | OR 0.91, 95% CI 0.76 to 1.09 |
| Abbreviations: AQLQ: asthma quality of life questionnaire; CI: confidence interval; ED: emergency department; HRQoL: health‐related quality of life; MD: mean difference; OR: odds ratio; RR: rate ratio. | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | 2039 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.47, 0.98] |
| 1.1.1 Tralokinumab 300 mg SC Q2W | 2 | 1435 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.41, 0.99] |
| 1.1.2 Tralokinumab 300 mg SC Q4W | 1 | 604 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.41, 1.49] |
| 1.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 7 | 4960 | Mean Difference (IV, Fixed, 95% CI) | 0.18 [0.12, 0.24] |
| 1.2.1 Lebrikizumab 125 mg SC Q4W | 1 | 209 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] |
| 1.2.2 Dupilumab 200 mg SC Q2W | 2 | 1111 | Mean Difference (IV, Fixed, 95% CI) | 0.29 [0.16, 0.42] |
| 1.2.3 Dupilumab 200 mg SC Q4W | 1 | 159 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐0.13, 0.59] |
| 1.2.4 Dupilumab 300 mg SC Q2W | 2 | 1127 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [0.14, 0.40] |
| 1.2.5 Dupilumab 300 mg SC Q4W | 1 | 164 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.06, 0.66] |
| 1.2.6 Tralokinumab 300 mg SC Q2W | 3 | 1262 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.00, 0.23] |
| 1.2.7 Tralokinumab 300 mg SC Q4W | 2 | 634 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.02, 0.30] |
| 1.2.8 AMG317 75 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.60, 0.36] |
| 1.2.9 AMG317 150 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.44, 0.58] |
| 1.2.10 AMG317 300 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.44, 0.64] |
| 1.3 Serious adverse events Show forest plot | 22 | 7739 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.91 [0.76, 1.09] |
| 1.3.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.3 Tralokinumab 1 mg/kg IV Q4W | 2 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.4 Tralokinumab 5 mg/kg IV Q4W | 2 | 14 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.02, 23.07] |
| 1.3.5 Tralokinumab 10 mg/kg IV Q4W | 2 | 10 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.29 [0.03, 53.51] |
| 1.3.6 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.05, 7.39] |
| 1.3.7 Tralokinumab 300 mg SC Q2W | 6 | 1955 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.78 [0.58, 1.05] |
| 1.3.8 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.58, 1.40] |
| 1.3.9 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.02, 5.42] |
| 1.3.10 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.16 [0.01, 1.76] |
| 1.3.11 Lebrikizumab 125 mg SC Q4W | 3 | 428 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.47 [0.43, 5.05] |
| 1.3.12 Lebrikizumab 250 mg SC Q4W | 3 | 445 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.28, 1.86] |
| 1.3.13 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.04, 27.64] |
| 1.3.14 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.06, 7.91] |
| 1.3.15 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.16 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.17 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.18 GSK679586 10 mg/kg IV Q4W | 2 | 206 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.52, 5.24] |
| 1.3.19 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.04, 38.30] |
| 1.3.20 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.21 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.22 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.03, 3.18] |
| 1.3.23 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.60, 1.54] |
| 1.3.24 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.15, 3.98] |
| 1.3.25 Dupilumab 300 mg SC Q2W | 3 | 1359 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.16 [0.76, 1.77] |
| 1.3.26 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.39, 5.06] |
| 1.3.27 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.3.28 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.04, 28.30] |
| 1.3.29 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.05, 9.70] |
| 1.3.30 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [0.12, 56.20] |
| 1.3.31 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.4 Exacerbation requiring OCS (rate ratio) Show forest plot | 1 | 452 | Rate Ratio (IV, Fixed, 95% CI) | 0.98 [0.72, 1.32] |
| 1.4.1 Tralokinumab 300 mg SC Q2W | 1 | 225 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.62, 1.42] |
| 1.4.2 Tralokinumab 300 mg SC Q4W | 1 | 227 | Rate Ratio (IV, Fixed, 95% CI) | 1.02 [0.65, 1.59] |
| 1.5 Exacerbation requiring OCS (dichotomous) Show forest plot | 2 | 453 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.49, 1.78] |
| 1.5.1 AMG317 75 mg SC | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.33, 3.88] |
| 1.5.2 AMG317 150 mg SC | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.47 [0.12, 1.83] |
| 1.5.3 AMG317 300 mg SC | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.14, 2.69] |
| 1.5.4 IMA638 75 mg SC | 1 | 68 | Odds Ratio (M‐H, Fixed, 95% CI) | 6.38 [0.34, 120.65] |
| 1.5.5 IMA638 200 mg SC | 1 | 26 | Odds Ratio (M‐H, Fixed, 95% CI) | 19.29 [0.65, 573.83] |
| 1.5.6 IMA638 0.2 mg/kg IV | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.5.7 IMA638 0.6 mg/kg IV | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.09 [0.00, 2.48] |
| 1.5.8 IMA638 2 mg/kg IV | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.33 [0.02, 6.37] |
| 1.6 Change from baseline in pre‐bronchodilator FEV1 Show forest plot | 13 | 4829 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [0.08, 0.12] |
| 1.6.1 Tralokinumab 150 mg SC Q2W | 1 | 58 | Mean Difference (IV, Fixed, 95% CI) | 0.09 [‐0.17, 0.35] |
| 1.6.2 Tralokinumab 300 mg SC Q2W | 3 | 331 | Mean Difference (IV, Fixed, 95% CI) | 0.13 [0.03, 0.22] |
| 1.6.3 Tralokinumab 300 mg SC Q4W | 1 | 185 | Mean Difference (IV, Fixed, 95% CI) | 0.04 [‐0.06, 0.14] |
| 1.6.4 Tralokinumab 600 mg SC Q2W | 1 | 58 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [‐0.07, 0.47] |
| 1.6.5 AMG317 75 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | ‐0.04 [‐0.18, 0.10] |
| 1.6.6 AMG317 150 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | 0.03 [‐0.15, 0.21] |
| 1.6.7 AMG317 300 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.03, 0.25] |
| 1.6.8 Lebrikizumab 125 mg SC Q4W | 2 | 279 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [0.01, 0.16] |
| 1.6.9 Lebrikizumab 250 mg SC Q4W | 2 | 288 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [0.03, 0.19] |
| 1.6.10 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Mean Difference (IV, Fixed, 95% CI) | 0.06 [‐0.11, 0.22] |
| 1.6.11 GSK679586 10 mg/kg IV Q4W | 1 | 198 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.19, ‐0.01] |
| 1.6.12 Dupilumab 300 mg SC Q1W | 1 | 104 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [0.11, 0.43] |
| 1.6.13 Dupilumab 200 mg SC Q2W | 2 | 1114 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [0.09, 0.20] |
| 1.6.14 Dupilumab 300 mg SC Q2W | 3 | 1329 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [0.10, 0.19] |
| 1.6.15 Dupilumab 200 mg SC Q4W | 1 | 157 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.04, 0.24] |
| 1.6.16 Dupilumab 300 mg SC Q4W | 1 | 164 | Mean Difference (IV, Fixed, 95% CI) | 0.13 [‐0.01, 0.27] |
| 1.6.17 IMA‐638 0.2 mg/kg IV | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.20, 0.40] |
| 1.6.18 IMA‐638 0.6 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.28, 0.28] |
| 1.6.19 IMA‐638 2 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.31, 0.31] |
| 1.6.20 IMA‐638 75 mg SC | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.11, 0.31] |
| 1.6.21 IMA‐638 200 mg SC | 1 | 86 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.13, 0.13] |
| 1.7 Change from baseline in ACQ score Show forest plot | 14 | 6251 | Mean Difference (IV, Fixed, 95% CI) | ‐0.19 [‐0.24, ‐0.14] |
| 1.7.1 Tralokinumab 150 mg SC Q2W | 1 | 61 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.72, 0.48] |
| 1.7.2 Tralokinumab 300 mg SC Q2W | 5 | 1484 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.21, ‐0.03] |
| 1.7.3 Tralokinumab 300 mg SC Q4W | 2 | 685 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.27, 0.02] |
| 1.7.4 Tralokinumab 600 mg SC Q2W | 1 | 63 | Mean Difference (IV, Fixed, 95% CI) | ‐0.25 [‐0.82, 0.32] |
| 1.7.5 AMG317 75 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | 0.06 [‐0.33, 0.45] |
| 1.7.6 AMG317 150 mg SC Q1W | 1 | 97 | Mean Difference (IV, Fixed, 95% CI) | ‐0.09 [‐0.51, 0.33] |
| 1.7.7 AMG317 300 mg SC Q1W | 1 | 98 | Mean Difference (IV, Fixed, 95% CI) | ‐0.21 [‐0.57, 0.15] |
| 1.7.8 Lebrikizumab 125 mg SC Q4W | 1 | 70 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐0.68, 0.28] |
| 1.7.9 Lebrikizumab 250 mg SC Q4W | 2 | 288 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.30, 0.17] |
| 1.7.10 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Mean Difference (IV, Fixed, 95% CI) | ‐0.40 [‐0.86, 0.06] |
| 1.7.11 GSK679586 10 mg/kg IV Q4W | 1 | 198 | Mean Difference (IV, Fixed, 95% CI) | ‐0.08 [‐0.31, 0.15] |
| 1.7.12 Dupilumab 300 mg SC Q1W | 1 | 104 | Mean Difference (IV, Fixed, 95% CI) | ‐0.73 [‐1.15, ‐0.31] |
| 1.7.13 Dupilumab 200 mg SC Q2W | 2 | 1114 | Mean Difference (IV, Fixed, 95% CI) | ‐0.38 [‐0.51, ‐0.25] |
| 1.7.14 Dupilumab 300 mg SC Q2W | 3 | 1341 | Mean Difference (IV, Fixed, 95% CI) | ‐0.27 [‐0.39, ‐0.15] |
| 1.7.15 Dupilumab 200 mg SC Q4W | 1 | 158 | Mean Difference (IV, Fixed, 95% CI) | ‐0.18 [‐0.53, 0.17] |
| 1.7.16 Dupilumab 300 mg SC Q4W | 1 | 163 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐0.54, 0.14] |
| 1.7.17 IMA‐638 0.2 mg/kg IV | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐1.12, 0.92] |
| 1.7.18 IMA‐638 0.6 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.75, 0.95] |
| 1.7.19 IMA‐638 2 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | ‐0.40 [‐1.25, 0.45] |
| 1.7.20 IMA‐638 75 mg SC | 1 | 8 | Mean Difference (IV, Fixed, 95% CI) | 0.60 [‐0.65, 1.85] |
| 1.7.21 IMA‐638 200 mg SC | 1 | 86 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [‐0.23, 0.63] |
| 1.8 Adverse events Show forest plot | 18 | 7419 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.16 [1.04, 1.30] |
| 1.8.1 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.48 [0.44, 5.01] |
| 1.8.2 Tralokinumab 300 mg SC Q2W | 5 | 1816 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.37 [1.11, 1.69] |
| 1.8.3 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.81 [0.57, 5.78] |
| 1.8.4 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.31 [0.95, 1.81] |
| 1.8.5 Tralokinumab 1 mg/kg IV | 1 | 9 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.8.6 Tralokinumab 5 mg/kg IV | 1 | 9 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.8.7 Tralokinumab 10 mg/kg IV | 1 | 4 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.8.8 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.16 [0.73, 6.37] |
| 1.8.9 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.50 [0.53, 4.26] |
| 1.8.10 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.07 [0.66, 6.46] |
| 1.8.11 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.18 [0.52, 2.67] |
| 1.8.12 Lebrikizumab 125 mg SC Q4W | 3 | 428 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.70, 1.64] |
| 1.8.13 Lebrikizumab 250 mg SC Q4W | 3 | 445 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.91 [0.58, 1.44] |
| 1.8.14 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.50 [0.47, 4.80] |
| 1.8.15 GSK679586 10 mg/kg IV Q4W | 1 | 198 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.65, 1.97] |
| 1.8.16 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.26 [0.49, 3.24] |
| 1.8.17 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.70, 1.33] |
| 1.8.18 Dupilumab 300 mg SC Q2W | 3 | 1358 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.89 [0.67, 1.18] |
| 1.8.19 Dupilumab 200 mg SC Q4W | 1 | 190 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.45, 2.28] |
| 1.8.20 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.60 [0.70, 3.67] |
| 1.8.21 VR492 0.5 mg | 1 | 11 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.06, 7.35] |
| 1.8.22 VR492 10 mg | 1 | 11 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.33 [0.03, 3.93] |
| 1.8.23 VR492 20 mg | 1 | 23 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.83 [0.28, 12.07] |
| 1.8.24 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.8.25 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.03, 29.81] |
| 1.9 Change from baseline in FENO, ppb Show forest plot | 11 | 3577 | Mean Difference (IV, Fixed, 95% CI) | ‐14.68 [‐16.56, ‐12.80] |
| 1.9.1 Lebrikizumab 125 mg SC Q4W | 2 | 279 | Mean Difference (IV, Fixed, 95% CI) | ‐21.25 [‐29.12, ‐13.37] |
| 1.9.2 Lebrikizumab 250 mg SC Q4W | 2 | 288 | Mean Difference (IV, Fixed, 95% CI) | ‐11.70 [‐17.34, ‐6.05] |
| 1.9.3 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Mean Difference (IV, Fixed, 95% CI) | ‐14.10 [‐32.86, 4.66] |
| 1.9.4 Tralokinumab 300 mg Q2W | 1 | 76 | Mean Difference (IV, Fixed, 95% CI) | ‐11.67 [‐20.32, ‐3.02] |
| 1.9.5 Dupilumab 200 mg SC Q2W | 2 | 1088 | Mean Difference (IV, Fixed, 95% CI) | ‐14.21 [‐17.27, ‐11.16] |
| 1.9.6 Dupilumab 300 mg SC Q2W | 3 | 1317 | Mean Difference (IV, Fixed, 95% CI) | ‐12.52 [‐16.61, ‐8.43] |
| 1.9.7 Dupilumab 200 mg SC Q4W | 1 | 132 | Mean Difference (IV, Fixed, 95% CI) | ‐16.39 [‐40.06, 7.28] |
| 1.9.8 Dupilumab 300 mg SC Q4W | 1 | 145 | Mean Difference (IV, Fixed, 95% CI) | ‐27.53 [‐51.21, ‐3.85] |
| 1.9.9 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Mean Difference (IV, Fixed, 95% CI) | ‐15.50 [‐57.42, 26.42] |
| 1.9.10 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Mean Difference (IV, Fixed, 95% CI) | ‐26.40 [‐67.03, 14.23] |
| 1.9.11 GSK679586 2.5 mg/kg IV Q4W | 2 | 8 | Mean Difference (IV, Fixed, 95% CI) | ‐28.00 [‐52.29, ‐3.71] |
| 1.9.12 GSK679586 10 mg/kg IV Q4W | 2 | 8 | Mean Difference (IV, Fixed, 95% CI) | ‐40.00 [‐55.96, ‐24.04] |
| 1.9.13 GSK679586 20 mg/kg IV Q4W | 2 | 96 | Mean Difference (IV, Fixed, 95% CI) | ‐24.14 [‐32.12, ‐16.15] |
| 1.9.14 VR492 0.5 mg | 1 | 11 | Mean Difference (IV, Fixed, 95% CI) | ‐3.80 [‐15.80, 8.20] |
| 1.9.15 VR492 10 mg | 1 | 11 | Mean Difference (IV, Fixed, 95% CI) | ‐17.50 [‐29.50, ‐5.50] |
| 1.9.16 VR492 20 mg | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐11.60 [‐20.50, ‐2.70] |
| 1.10 Change from baseline in blood eosinophils, cells x 10*9/L Show forest plot | 6 | 2598 | Mean Difference (IV, Fixed, 95% CI) | 0.06 [0.04, 0.09] |
| 1.10.1 Tralokinumab 300 mg Q2W | 1 | 76 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [‐0.02, 0.18] |
| 1.10.2 Lebrikizumab 250 mg SC Q4W | 1 | 218 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [0.06, 0.16] |
| 1.10.3 Dupilumab 300 mg SC Q1W | 1 | 87 | Mean Difference (IV, Fixed, 95% CI) | 0.17 [‐0.02, 0.36] |
| 1.10.4 Dupilumab 200 mg SC Q2W | 1 | 944 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.03, 0.06] |
| 1.10.5 Dupilumab 300 mg SC Q2W | 1 | 953 | Mean Difference (IV, Fixed, 95% CI) | 0.04 [‐0.01, 0.09] |
| 1.10.6 IMA‐638 0.2 mg/kg IV | 1 | 21 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.10, 0.30] |
| 1.10.7 IMA‐638 0.6 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [0.00, 0.40] |
| 1.10.8 IMA‐638 2 mg/kg IV | 1 | 22 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.09, 0.29] |
| 1.10.9 IMA‐638 75 mg SC | 1 | 8 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [‐1.13, 1.53] |
| 1.10.10 IMA‐638 200 mg SC | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.10, 0.30] |
| 1.10.11 GSK679586 10 mg/kg IV | 1 | 198 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [‐0.00, 0.16] |
| 1.11 Change from baseline in periostin, ng/mL Show forest plot | 2 | 2106 | Mean Difference (IV, Fixed, 95% CI) | ‐9.04 [‐10.92, ‐7.17] |
| 1.11.1 Lebrikizumab 125 mg SC Q4W | 1 | 209 | Mean Difference (IV, Fixed, 95% CI) | ‐4.20 [‐6.84, ‐1.56] |
| 1.11.2 Dupilumab 200 mg SC Q2W | 1 | 944 | Mean Difference (IV, Fixed, 95% CI) | ‐14.06 [‐17.70, ‐10.42] |
| 1.11.3 Dupilumab 300 mg SC Q2W | 1 | 953 | Mean Difference (IV, Fixed, 95% CI) | ‐13.85 [‐17.73, ‐9.97] |
| 1.12 Percentage reduction from baseline in OCS use Show forest plot | 2 | 350 | Mean Difference (IV, Fixed, 95% CI) | ‐15.58 [‐23.30, ‐7.85] |
| 1.12.1 Tralokinumab 300 mg SC Q2W | 1 | 140 | Mean Difference (IV, Fixed, 95% CI) | ‐7.77 [‐17.60, 2.06] |
| 1.12.2 Dupilumab 300 mg SC Q2W | 1 | 210 | Mean Difference (IV, Fixed, 95% CI) | ‐28.20 [‐40.70, ‐15.70] |
| 1.13 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 7 | 6998 | Rate Ratio (IV, Fixed, 95% CI) | 0.71 [0.65, 0.77] |
| 1.13.1 Tralokinumab 300 mg SC Q2W | 3 | 1575 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.80, 1.11] |
| 1.13.2 Tralokinumab 300 mg SC Q4W | 1 | 604 | Rate Ratio (IV, Fixed, 95% CI) | 0.90 [0.66, 1.22] |
| 1.13.3 Lebrikizumab 37.5 mg SC Q4W | 2 | 1074 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.53, 0.87] |
| 1.13.4 Lebrikizumab 125 mg SC Q4W | 2 | 1074 | Rate Ratio (IV, Fixed, 95% CI) | 0.74 [0.59, 0.93] |
| 1.13.5 Dupilumab 200mg SC Q2W | 2 | 1135 | Rate Ratio (IV, Fixed, 95% CI) | 0.51 [0.40, 0.64] |
| 1.13.6 Dupilumab 200 mg SC Q4W | 1 | 195 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.18, 1.16] |
| 1.13.7 Dupilumab 300mg SC Q2W | 2 | 1144 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.42, 0.65] |
| 1.13.8 Dupilumab 300 mg SC Q4W | 1 | 197 | Rate Ratio (IV, Fixed, 95% CI) | 0.67 [0.29, 1.55] |
| 1.14 Exacerbation requiring hospitalisation/ED/OCS (relative risk) Show forest plot | 1 | 210 | Risk Ratio (IV, Fixed, 95% CI) | 0.41 [0.26, 0.63] |
| 1.14.1 Dupilumab 300mg SC Q2W | 1 | 210 | Risk Ratio (IV, Fixed, 95% CI) | 0.41 [0.26, 0.63] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.47, 0.98] | |
| 2.1.1 Tralokinumab 300 mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.41, 0.99] | |
| 2.1.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.41, 1.49] | |
| 2.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 4 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [0.01, 0.18] | |
| 2.2.1 Lebrikizumab 125 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 2.2.2 Tralokinumab 300 mg SC Q2W | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.00, 0.23] | |
| 2.2.3 Tralokinumab 300 mg SC Q4W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.02, 0.30] | |
| 2.3 Serious adverse events Show forest plot | 16 | 4443 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.67, 1.05] |
| 2.3.1 Tralokinumab 1 mg/kg IV Q4W | 2 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.3.2 Tralokinumab 5 mg/kg IV Q4W | 2 | 14 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.02, 23.07] |
| 2.3.3 Tralokinumab 10 mg/kg IV Q4W | 2 | 10 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.29 [0.03, 53.51] |
| 2.3.4 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.05, 7.39] |
| 2.3.5 Tralokinumab 300 mg SC Q2W | 6 | 1955 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.78 [0.58, 1.05] |
| 2.3.6 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.58, 1.40] |
| 2.3.7 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.02, 5.42] |
| 2.3.8 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.16 [0.01, 1.76] |
| 2.3.9 Lebrikizumab 125 mg SC Q4W | 3 | 428 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.47 [0.43, 5.05] |
| 2.3.10 Lebrikizumab 250 mg SC Q4W | 3 | 445 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.28, 1.86] |
| 2.3.11 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.04, 27.64] |
| 2.3.12 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.3.13 GSK679586 10 mg/kg IV Q4W | 2 | 206 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.52, 5.24] |
| 2.3.14 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.04, 38.30] |
| 2.3.15 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.3.16 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.3.17 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.3.18 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.04, 28.30] |
| 2.3.19 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.05, 9.70] |
| 2.3.20 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [0.12, 56.20] |
| 2.3.21 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.4 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 5 | Rate Ratio (IV, Fixed, 95% CI) | 0.83 [0.74, 0.92] | |
| 2.4.1 Tralokinumab 300 mg SC Q2W | 3 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.80, 1.11] | |
| 2.4.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.90 [0.66, 1.22] | |
| 2.4.3 Lebrikizumab 37.5 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.53, 0.87] | |
| 2.4.4 Lebrikizumab 125 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.74 [0.59, 0.93] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [0.17, 0.34] | |
| 3.1.1 Dupilumab 200 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.29 [0.16, 0.42] | |
| 3.1.2 Dupilumab 200 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐0.13, 0.59] | |
| 3.1.3 Dupilumab 300 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [0.14, 0.40] | |
| 3.1.4 Dupilumab 300 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.06, 0.66] | |
| 3.1.5 AMG317 75 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.60, 0.36] | |
| 3.1.6 AMG317 150 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.44, 0.58] | |
| 3.1.7 AMG317 300 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.44, 0.64] | |
| 3.2 Serious adverse events Show forest plot | 6 | 3296 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.78, 1.40] |
| 3.2.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 3.2.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 3.2.3 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.06, 7.91] |
| 3.2.4 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 3.2.5 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 3.2.6 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.03, 3.18] |
| 3.2.7 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.60, 1.54] |
| 3.2.8 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.15, 3.98] |
| 3.2.9 Dupilumab 300 mg SC Q2W | 3 | 1359 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.16 [0.76, 1.77] |
| 3.2.10 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.39, 5.06] |
| 3.3 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.44, 0.61] | |
| 3.3.1 Dupilumab 200mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.51 [0.40, 0.64] | |
| 3.3.2 Dupilumab 200 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.18, 1.16] | |
| 3.3.3 Dupilumab 300mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.42, 0.65] | |
| 3.3.4 Dupilumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.67 [0.29, 1.55] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.13 [‐0.00, 0.26] | |
| 4.1.1 Lebrikizumab 125 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 4.1.2 Dupilumab 200 mg SC Q2W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.31 [‐0.06, 0.68] | |
| 4.1.3 Dupilumab 200 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐0.13, 0.59] | |
| 4.1.4 Dupilumab 300 mg SC Q2W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.36 [‐0.02, 0.74] | |
| 4.1.5 Dupilumab 300 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.06, 0.66] | |
| 4.1.6 AMG317 75 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.60, 0.36] | |
| 4.1.7 AMG317 150 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.44, 0.58] | |
| 4.1.8 AMG317 300 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.44, 0.64] | |
| 4.2 Serious adverse events Show forest plot | 16 | 2738 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.09 [0.73, 1.63] |
| 4.2.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.3 Tralokinumab 1 mg/kg IV Q4W | 2 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.4 Tralokinumab 5 mg/kg IV Q4W | 2 | 14 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.02, 23.07] |
| 4.2.5 Tralokinumab 10 mg/kg IV Q4W | 2 | 10 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.29 [0.03, 53.51] |
| 4.2.6 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.05, 7.39] |
| 4.2.7 Tralokinumab 300 mg SC Q2W | 2 | 145 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.19 [0.02, 1.89] |
| 4.2.8 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.02, 5.42] |
| 4.2.9 Lebrikizumab 125 mg SC Q4W | 2 | 277 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.18 [0.33, 14.31] |
| 4.2.10 Lebrikizumab 250 mg SC Q4W | 2 | 288 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.19, 2.53] |
| 4.2.11 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.04, 27.64] |
| 4.2.12 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.06, 7.91] |
| 4.2.13 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.14 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.15 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.16 GSK679586 10 mg/kg IV Q4W | 2 | 206 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.52, 5.24] |
| 4.2.17 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.04, 38.30] |
| 4.2.18 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.19 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.20 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.03, 3.18] |
| 4.2.21 Dupilumab 200 mg SC Q2W | 1 | 187 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.34 [0.28, 6.39] |
| 4.2.22 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.15, 3.98] |
| 4.2.23 Dupilumab 300 mg SC Q2W | 2 | 406 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.69, 3.97] |
| 4.2.24 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.39, 5.06] |
| 4.2.25 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.2.26 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.04, 28.30] |
| 4.2.27 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.05, 9.70] |
| 4.2.28 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [0.12, 56.20] |
| 4.2.29 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 4.3 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.43 [0.27, 0.68] | |
| 4.3.1 Dupilumab 200mg SC Q2W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.30 [0.11, 0.82] | |
| 4.3.2 Dupilumab 200 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.18, 1.16] | |
| 4.3.3 Dupilumab 300mg SC Q2W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.29 [0.11, 0.78] | |
| 4.3.4 Dupilumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.67 [0.29, 1.55] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.47, 0.98] | |
| 5.1.1 Tralokinumab 300 mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.41, 0.99] | |
| 5.1.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.41, 1.49] | |
| 5.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 4 | Mean Difference (IV, Fixed, 95% CI) | 0.19 [0.13, 0.26] | |
| 5.2.1 Dupilumab 200 mg SC Q2W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.29 [0.15, 0.43] | |
| 5.2.2 Dupilumab 300 mg SC Q2W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [0.12, 0.40] | |
| 5.2.3 Tralokinumab 300 mg SC Q2W | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.00, 0.23] | |
| 5.2.4 Tralokinumab 300 mg SC Q4W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.02, 0.30] | |
| 5.3 Serious adverse events Show forest plot | 6 | 5001 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.72, 1.06] |
| 5.3.1 Tralokinumab 300 mg SC Q2W | 4 | 1810 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.80 [0.59, 1.09] |
| 5.3.2 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.58, 1.40] |
| 5.3.3 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.16 [0.01, 1.76] |
| 5.3.4 Lebrikizumab 125 mg SC Q4W | 1 | 151 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.20, 5.42] |
| 5.3.5 Lebrikizumab 250 mg SC Q4W | 1 | 157 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.76 [0.19, 3.08] |
| 5.3.6 Dupilumab 200 mg SC Q2W | 1 | 944 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.57, 1.53] |
| 5.3.7 Dupilumab 200 mg SC Q4W | 0 | 0 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 5.3.8 Dupilumab 300 mg SC Q2W | 1 | 953 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.64, 1.68] |
| 5.4 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 6 | Rate Ratio (IV, Fixed, 95% CI) | 0.72 [0.66, 0.79] | |
| 5.4.1 Tralokinumab 300 mg SC Q2W | 3 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.80, 1.11] | |
| 5.4.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.90 [0.66, 1.22] | |
| 5.4.3 Lebrikizumab 37.5 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.53, 0.87] | |
| 5.4.4 Lebrikizumab 125 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.74 [0.59, 0.93] | |
| 5.4.5 Dupilumab 200mg SC Q2W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.41, 0.66] | |
| 5.4.6 Dupilumab 300mg SC Q2W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.54 [0.43, 0.68] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 6.1.1 Lebrikizumab 125 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 6.2 Serious adverse events Show forest plot | 7 | 664 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.41 [0.49, 4.01] |
| 6.2.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.3 Tralokinumab 1 mg/kg IV Q4W | 1 | 9 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.4 Tralokinumab 5 mg/kg IV Q4W | 1 | 9 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.02, 23.07] |
| 6.2.5 Tralokinumab 10 mg/kg IV Q4W | 1 | 5 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.6 Lebrikizumab 125 mg SC Q4W | 2 | 277 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.18 [0.33, 14.31] |
| 6.2.7 Lebrikizumab 250 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.8 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.04, 27.64] |
| 6.2.9 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.10 GSK679586 10 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.11 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.04, 38.30] |
| 6.2.12 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.13 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.14 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.2.15 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.04, 28.30] |
| 6.2.16 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.05, 9.70] |
| 6.2.17 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [0.12, 56.20] |
| 6.2.18 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.47, 0.98] | |
| 7.1.1 Tralokinumab 300 mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.41, 0.99] | |
| 7.1.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.41, 1.49] | |
| 7.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 5 | Mean Difference (IV, Fixed, 95% CI) | 0.21 [0.14, 0.27] | |
| 7.2.1 Dupilumab 200 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.29 [0.16, 0.42] | |
| 7.2.2 Dupilumab 200 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐0.13, 0.59] | |
| 7.2.3 Dupilumab 300 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [0.14, 0.40] | |
| 7.2.4 Dupilumab 300 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.06, 0.66] | |
| 7.2.5 Tralokinumab 300 mg SC Q2W | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.00, 0.23] | |
| 7.2.6 Tralokinumab 300 mg SC Q4W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.02, 0.30] | |
| 7.3 Serious adverse events Show forest plot | 10 | 5946 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.78, 1.13] |
| 7.3.1 Tralokinumab 1 mg/kg IV Q4W | 1 | 3 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 7.3.2 Tralokinumab 5 mg/kg IV Q4W | 1 | 5 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 7.3.3 Tralokinumab 10 mg/kg IV Q4W | 1 | 5 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.29 [0.03, 53.51] |
| 7.3.4 Tralokinumab 300 mg SC Q2W | 4 | 1810 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.80 [0.59, 1.09] |
| 7.3.5 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.58, 1.40] |
| 7.3.6 Lebrikizumab 250 mg SC Q4W | 1 | 218 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.19, 2.53] |
| 7.3.7 GSK679586 10 mg/kg IV Q4W | 1 | 198 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.52, 5.24] |
| 7.3.8 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.60, 1.54] |
| 7.3.9 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.15, 3.98] |
| 7.3.10 Dupilumab 300 mg SC Q2W | 3 | 1359 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.16 [0.76, 1.77] |
| 7.3.11 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.39, 5.06] |
| 7.4 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 7 | Rate Ratio (IV, Fixed, 95% CI) | 0.71 [0.65, 0.77] | |
| 7.4.1 Tralokinumab 300 mg SC Q2W | 3 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.80, 1.11] | |
| 7.4.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.90 [0.66, 1.22] | |
| 7.4.3 Lebrikizumab 37.5 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.53, 0.87] | |
| 7.4.4 Lebrikizumab 125 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.74 [0.59, 0.93] | |
| 7.4.5 Dupilumab 200mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.51 [0.40, 0.64] | |
| 7.4.6 Dupilumab 200 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.18, 1.16] | |
| 7.4.7 Dupilumab 300mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.42, 0.65] | |
| 7.4.8 Dupilumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.67 [0.29, 1.55] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 8.1.1 Lebrikizumab 125 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 8.2 Serious adverse events Show forest plot | 4 | 470 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.73 [0.40, 7.48] |
| 8.2.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 8.2.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 8.2.3 Lebrikizumab 125 mg SC Q4W | 2 | 277 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.18 [0.33, 14.31] |
| 8.2.4 Lebrikizumab 250 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 8.2.5 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.04, 27.64] |
| 8.2.6 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 8.2.7 GSK679586 10 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 8.2.8 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.04, 38.30] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.47, 0.98] | |
| 9.1.1 Tralokinumab 300 mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.41, 0.99] | |
| 9.1.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.41, 1.49] | |
| 9.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 6 | Mean Difference (IV, Fixed, 95% CI) | 0.20 [0.13, 0.26] | |
| 9.2.1 Dupilumab 200 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.29 [0.16, 0.42] | |
| 9.2.2 Dupilumab 200 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐0.13, 0.59] | |
| 9.2.3 Dupilumab 300 mg SC Q2W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [0.14, 0.40] | |
| 9.2.4 Dupilumab 300 mg SC Q4W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.06, 0.66] | |
| 9.2.5 Tralokinumab 300 mg SC Q2W | 3 | Mean Difference (IV, Fixed, 95% CI) | 0.11 [‐0.00, 0.23] | |
| 9.2.6 Tralokinumab 300 mg SC Q4W | 2 | Mean Difference (IV, Fixed, 95% CI) | 0.14 [‐0.02, 0.30] | |
| 9.2.7 AMG317 75 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.60, 0.36] | |
| 9.2.8 AMG317 150 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.07 [‐0.44, 0.58] | |
| 9.2.9 AMG317 300 mg SC Q1W | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.44, 0.64] | |
| 9.3 Serious adverse events Show forest plot | 18 | 7269 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.76, 1.08] |
| 9.3.1 Tralokinumab 1 mg/kg IV Q4W | 2 | 12 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.2 Tralokinumab 5 mg/kg IV Q4W | 2 | 14 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.02, 23.07] |
| 9.3.3 Tralokinumab 10 mg/kg IV Q4W | 2 | 10 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.29 [0.03, 53.51] |
| 9.3.4 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.05, 7.39] |
| 9.3.5 Tralokinumab 300 mg SC Q2W | 6 | 1955 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.78 [0.58, 1.05] |
| 9.3.6 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.58, 1.40] |
| 9.3.7 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.02, 5.42] |
| 9.3.8 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.16 [0.01, 1.76] |
| 9.3.9 Lebrikizumab 125 mg SC Q4W | 1 | 151 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.20, 5.42] |
| 9.3.10 Lebrikizumab 250 mg SC Q4W | 2 | 375 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.28, 1.86] |
| 9.3.11 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.06, 7.91] |
| 9.3.12 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.13 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.14 GSK679586 10 mg/kg IV Q4W | 1 | 198 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [0.52, 5.24] |
| 9.3.15 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.16 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.17 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.32 [0.03, 3.18] |
| 9.3.18 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.60, 1.54] |
| 9.3.19 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.15, 3.98] |
| 9.3.20 Dupilumab 300 mg SC Q2W | 3 | 1359 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.16 [0.76, 1.77] |
| 9.3.21 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.39, 5.06] |
| 9.3.22 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.3.23 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.04, 28.30] |
| 9.3.24 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.05, 9.70] |
| 9.3.25 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [0.12, 56.20] |
| 9.3.26 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 9.4 Exacerbation requiring hospitalisation/ED/OCS (rate ratio) Show forest plot | 7 | Rate Ratio (IV, Fixed, 95% CI) | 0.71 [0.65, 0.77] | |
| 9.4.1 Tralokinumab 300 mg SC Q2W | 3 | Rate Ratio (IV, Fixed, 95% CI) | 0.94 [0.80, 1.11] | |
| 9.4.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.90 [0.66, 1.22] | |
| 9.4.3 Lebrikizumab 37.5 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.68 [0.53, 0.87] | |
| 9.4.4 Lebrikizumab 125 mg SC Q4W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.74 [0.59, 0.93] | |
| 9.4.5 Dupilumab 200mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.51 [0.40, 0.64] | |
| 9.4.6 Dupilumab 200 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.18, 1.16] | |
| 9.4.7 Dupilumab 300mg SC Q2W | 2 | Rate Ratio (IV, Fixed, 95% CI) | 0.52 [0.42, 0.65] | |
| 9.4.8 Dupilumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.67 [0.29, 1.55] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Blood eosinophils high (> 300 cells/uL) Show forest plot | 5 | 2052 | Rate Ratio (IV, Fixed, 95% CI) | 0.47 [0.40, 0.55] |
| 10.1.1 Dupilumab 200 mg Q2W | 2 | 494 | Rate Ratio (IV, Fixed, 95% CI) | 0.34 [0.24, 0.47] |
| 10.1.2 Dupilumab 200 mg Q4W | 1 | 77 | Rate Ratio (IV, Fixed, 95% CI) | 0.34 [0.07, 1.63] |
| 10.1.3 Dupilumab 300 mg Q2W | 3 | 589 | Rate Ratio (IV, Fixed, 95% CI) | 0.46 [0.36, 0.59] |
| 10.1.4 Dupilumab 300 mg Q4W | 1 | 83 | Rate Ratio (IV, Fixed, 95% CI) | 0.65 [0.17, 2.44] |
| 10.1.5 Lebrikizumab 37.5 mg Q4W | 2 | 398 | Rate Ratio (IV, Fixed, 95% CI) | 0.54 [0.38, 0.76] |
| 10.1.6 Lebrikizumab 125 mg Q4W | 2 | 411 | Rate Ratio (IV, Fixed, 95% CI) | 0.59 [0.42, 0.83] |
| 10.2 Blood eosinophils low (< 300 cells/uL) Show forest plot | 4 | 1881 | Rate Ratio (IV, Fixed, 95% CI) | 0.75 [0.65, 0.87] |
| 10.2.1 Dupilumab 200 mg Q2W | 1 | 107 | Rate Ratio (IV, Fixed, 95% CI) | 0.32 [0.09, 1.21] |
| 10.2.2 Dupilumab 200 mg Q4W | 1 | 114 | Rate Ratio (IV, Fixed, 95% CI) | 0.57 [0.19, 1.75] |
| 10.2.3 Dupilumab 300 mg Q2W | 2 | 237 | Rate Ratio (IV, Fixed, 95% CI) | 0.69 [0.56, 0.86] |
| 10.2.4 Dupilumab 300 mg Q4W | 1 | 114 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.21, 1.85] |
| 10.2.5 Lebrikizumab 37.5 mg Q4W | 2 | 645 | Rate Ratio (IV, Fixed, 95% CI) | 0.79 [0.58, 1.08] |
| 10.2.6 Lebrikizumab 125 mg Q4W | 2 | 664 | Rate Ratio (IV, Fixed, 95% CI) | 0.92 [0.68, 1.23] |
| 10.3 Blood eosinophils low (> 150 < 300 cells/uL) Show forest plot | 1 | 527 | Rate Ratio (IV, Fixed, 95% CI) | 0.60 [0.43, 0.83] |
| 10.3.1 Dupilumab 200 mg Q2W | 1 | 257 | Rate Ratio (IV, Fixed, 95% CI) | 0.64 [0.41, 1.00] |
| 10.3.2 Dupilumab 300 mg Q2W | 1 | 270 | Rate Ratio (IV, Fixed, 95% CI) | 0.56 [0.35, 0.90] |
| 10.4 Blood eosinophils low (< 150 cells/uL) Show forest plot | 1 | 542 | Rate Ratio (IV, Fixed, 95% CI) | 1.05 [0.76, 1.43] |
| 10.4.1 Dupilumab 200 mg Q2W | 1 | 278 | Rate Ratio (IV, Fixed, 95% CI) | 0.93 [0.58, 1.49] |
| 10.4.2 Dupilumab 300 mg Q2W | 1 | 264 | Rate Ratio (IV, Fixed, 95% CI) | 1.15 [0.75, 1.76] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 FENO high (≥ 50 ppb) Show forest plot | 1 | 389 | Rate Ratio (IV, Fixed, 95% CI) | 0.31 [0.22, 0.45] |
| 11.1.1 Dupilumab 200 mg Q2W | 1 | 190 | Rate Ratio (IV, Fixed, 95% CI) | 0.31 [0.18, 0.53] |
| 11.1.2 Dupilumab 300 mg Q2W | 1 | 199 | Rate Ratio (IV, Fixed, 95% CI) | 0.31 [0.19, 0.51] |
| 11.2 FENO medium (≥ 25 to < 50 ppb) Show forest plot | 1 | 554 | Rate Ratio (IV, Fixed, 95% CI) | 0.42 [0.30, 0.58] |
| 11.2.1 Dupilumab 200 mg Q2W | 1 | 271 | Rate Ratio (IV, Fixed, 95% CI) | 0.39 [0.24, 0.63] |
| 11.2.2 Dupilumab 300 mg Q2W | 1 | 283 | Rate Ratio (IV, Fixed, 95% CI) | 0.44 [0.28, 0.69] |
| 11.3 FENO low (< 25 ppb) Show forest plot | 1 | 935 | Rate Ratio (IV, Fixed, 95% CI) | 0.77 [0.61, 0.97] |
| 11.3.1 Dupilumab 200 mg Q2W | 1 | 474 | Rate Ratio (IV, Fixed, 95% CI) | 0.75 [0.54, 1.04] |
| 11.3.2 Dupilumab 300 mg Q2W | 1 | 461 | Rate Ratio (IV, Fixed, 95% CI) | 0.79 [0.57, 1.09] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 12.1 Periostin high (≥ 50 ng/mL) Show forest plot | 3 | 1499 | Rate Ratio (IV, Fixed, 95% CI) | 0.63 [0.51, 0.77] |
| 12.1.1 Lebrikizumab 37.5 mg | 3 | 717 | Rate Ratio (IV, Fixed, 95% CI) | 0.59 [0.43, 0.79] |
| 12.1.2 Lebrikizumab 125 mg | 3 | 715 | Rate Ratio (IV, Fixed, 95% CI) | 0.66 [0.49, 0.89] |
| 12.1.3 Lebrikizumab 250 mg | 1 | 67 | Rate Ratio (IV, Fixed, 95% CI) | 0.78 [0.27, 2.24] |
| 12.2 Periostin low (< 50 ng/mL) Show forest plot | 3 | 1212 | Rate Ratio (IV, Fixed, 95% CI) | 0.87 [0.68, 1.11] |
| 12.2.1 Lebrikizumab 37.5 mg | 3 | 562 | Rate Ratio (IV, Fixed, 95% CI) | 0.79 [0.54, 1.15] |
| 12.2.2 Lebrikizumab 125 mg | 3 | 560 | Rate Ratio (IV, Fixed, 95% CI) | 0.93 [0.66, 1.32] |
| 12.2.3 Lebrikizumab 250 mg | 1 | 90 | Rate Ratio (IV, Fixed, 95% CI) | 0.95 [0.30, 3.00] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 13.1 Exacerbation requiring hospitalisation or ED visit Show forest plot | 2 | Rate Ratio (IV, Random, 95% CI) | 0.68 [0.47, 0.98] | |
| 13.1.1 Tralokinumab 300 mg SC Q2W | 2 | Rate Ratio (IV, Random, 95% CI) | 0.63 [0.41, 0.99] | |
| 13.1.2 Tralokinumab 300 mg SC Q4W | 1 | Rate Ratio (IV, Random, 95% CI) | 0.78 [0.41, 1.49] | |
| 13.2 Health‐related quality of life (adjusted mean diff versus placebo) Show forest plot | 7 | Mean Difference (IV, Random, 95% CI) | 0.18 [0.12, 0.24] | |
| 13.2.1 Lebrikizumab 125 mg SC Q4W | 1 | Mean Difference (IV, Random, 95% CI) | ‐0.06 [‐0.29, 0.17] | |
| 13.2.2 Dupilumab 200 mg SC Q2W | 2 | Mean Difference (IV, Random, 95% CI) | 0.29 [0.16, 0.42] | |
| 13.2.3 Dupilumab 200 mg SC Q4W | 1 | Mean Difference (IV, Random, 95% CI) | 0.23 [‐0.13, 0.59] | |
| 13.2.4 Dupilumab 300 mg SC Q2W | 2 | Mean Difference (IV, Random, 95% CI) | 0.27 [0.14, 0.40] | |
| 13.2.5 Dupilumab 300 mg SC Q4W | 1 | Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.06, 0.66] | |
| 13.2.6 Tralokinumab 300 mg SC Q2W | 3 | Mean Difference (IV, Random, 95% CI) | 0.11 [‐0.00, 0.23] | |
| 13.2.7 Tralokinumab 300 mg SC Q4W | 2 | Mean Difference (IV, Random, 95% CI) | 0.14 [‐0.02, 0.30] | |
| 13.2.8 AMG317 75 mg SC Q1W | 1 | Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐0.60, 0.36] | |
| 13.2.9 AMG317 150 mg SC Q1W | 1 | Mean Difference (IV, Random, 95% CI) | 0.07 [‐0.44, 0.58] | |
| 13.2.10 AMG317 300 mg SC Q1W | 1 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.44, 0.64] | |
| 13.3 Serious adverse events Show forest plot | 22 | 7739 | Odds Ratio (M‐H, Random, 95% CI) | 0.91 [0.76, 1.09] |
| 13.3.1 Soluble IL‐4R 500 ug nebulised | 1 | 12 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.2 Soluble IL‐4R 1500 ug nebulised | 1 | 13 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.3 Tralokinumab 1 mg/kg IV Q4W | 2 | 12 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.4 Tralokinumab 5 mg/kg IV Q4W | 2 | 14 | Odds Ratio (M‐H, Random, 95% CI) | 0.60 [0.02, 23.07] |
| 13.3.5 Tralokinumab 10 mg/kg IV Q4W | 2 | 10 | Odds Ratio (M‐H, Random, 95% CI) | 1.29 [0.03, 53.51] |
| 13.3.6 Tralokinumab 150 mg SC Q2W | 1 | 62 | Odds Ratio (M‐H, Random, 95% CI) | 0.62 [0.05, 7.39] |
| 13.3.7 Tralokinumab 300 mg SC Q2W | 6 | 1955 | Odds Ratio (M‐H, Random, 95% CI) | 0.78 [0.58, 1.06] |
| 13.3.8 Tralokinumab 300 mg SC Q4W | 2 | 831 | Odds Ratio (M‐H, Random, 95% CI) | 0.89 [0.58, 1.39] |
| 13.3.9 Tralokinumab 600 mg SC Q2W | 1 | 64 | Odds Ratio (M‐H, Random, 95% CI) | 0.32 [0.02, 5.42] |
| 13.3.10 Lebrikizumab 37.5 mg SC Q4W | 1 | 155 | Odds Ratio (M‐H, Random, 95% CI) | 0.16 [0.01, 1.76] |
| 13.3.11 Lebrikizumab 125 mg SC Q4W | 3 | 428 | Odds Ratio (M‐H, Random, 95% CI) | 1.43 [0.41, 4.94] |
| 13.3.12 Lebrikizumab 250 mg SC Q4W | 3 | 445 | Odds Ratio (M‐H, Random, 95% CI) | 0.72 [0.28, 1.87] |
| 13.3.13 Lebrikizumab 500 mg SC Q4W | 1 | 70 | Odds Ratio (M‐H, Random, 95% CI) | 1.08 [0.04, 27.64] |
| 13.3.14 AMG317 75 mg SC Q1W | 1 | 97 | Odds Ratio (M‐H, Random, 95% CI) | 0.69 [0.06, 7.91] |
| 13.3.15 AMG317 150 mg SC Q1W | 1 | 98 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.16 AMG317 300 mg SC Q1W | 1 | 96 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.17 GSK679586 2.5 mg/kg IV Q4W | 1 | 8 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.18 GSK679586 10 mg/kg IV Q4W | 2 | 206 | Odds Ratio (M‐H, Random, 95% CI) | 1.65 [0.52, 5.24] |
| 13.3.19 GSK679586 20 mg/kg IV Q4W | 1 | 12 | Odds Ratio (M‐H, Random, 95% CI) | 1.24 [0.04, 38.30] |
| 13.3.20 RPC4046 0.3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.21 RPC4046 3 mg/kg IV Q1W | 1 | 6 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.22 Dupilumab 300 mg SC Q1W | 1 | 104 | Odds Ratio (M‐H, Random, 95% CI) | 0.32 [0.03, 3.18] |
| 13.3.23 Dupilumab 200 mg SC Q2W | 2 | 1131 | Odds Ratio (M‐H, Random, 95% CI) | 0.96 [0.60, 1.54] |
| 13.3.24 Dupilumab 200 mg SC Q4W | 1 | 189 | Odds Ratio (M‐H, Random, 95% CI) | 0.77 [0.15, 3.98] |
| 13.3.25 Dupilumab 300 mg SC Q2W | 3 | 1359 | Odds Ratio (M‐H, Random, 95% CI) | 1.16 [0.76, 1.76] |
| 13.3.26 Dupilumab 300 mg SC Q4W | 1 | 197 | Odds Ratio (M‐H, Random, 95% CI) | 1.40 [0.39, 5.06] |
| 13.3.27 IMA‐638 IV 0.2 mg/kg (D1/8/28/56/84) | 1 | 21 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
| 13.3.28 IMA‐638 IV 0.6 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Random, 95% CI) | 1.00 [0.04, 28.30] |
| 13.3.29 IMA‐638 IV 2 mg/kg (D1/8/28/56/84) | 1 | 22 | Odds Ratio (M‐H, Random, 95% CI) | 0.71 [0.05, 9.70] |
| 13.3.30 IMA‐638 IV 200 mg SC (D1/8/28/42/56/70/84) | 1 | 67 | Odds Ratio (M‐H, Random, 95% CI) | 2.59 [0.12, 56.20] |
| 13.3.31 IMA‐638 IV 75 mg SC (D1/8/28/42/56/70/84) | 1 | 27 | Odds Ratio (M‐H, Random, 95% CI) | Not estimable |
