Menu

nma-hero-image nma-hero-image

NMA class comparison data in COPD

UMEC/VI versus dual and mono-bronchodilator therapies

Key outcomes of interest1

figure-showing-key-outcomes-of-interest.-UMEC/VI (62.5/25-micrograms)-was-compared-to-other-dual-and-mono-therapies.-The-outcomes-of-interest-include-mean-difference-in-change-from-baseline-in-trough-FEV1-at-weeks-12-and-24,-mean-difference-in-change-from-baseline-in-SGRQ-total-score-at-week-24,-mean-difference-in-change-from-baseline-in-TDI-focal-score-at-week-24-and-mean-difference-in-rescue-medication-use-at-week-24

TDI: Mean difference in CFB in TDI focal score at week 24

figure-showing-key-outcomes-of-interest.-UMEC/VI (62.5/25-micrograms)-was-compared-to-other-dual-and-mono-therapies.-The-outcomes-of-interest-include-mean-difference-in-change-from-baseline-in-trough-FEV1-at-weeks-12-and-24,-mean-difference-in-change-from-baseline-in-SGRQ-total-score-at-week-24,-mean-difference-in-change-from-baseline-in-TDI-focal-score-at-week-24-and-mean-difference-in-rescue-medication-use-at-week-24

Lung function: Mean differnce in CFB in trough FEV1 at weeks 12 and 24

figure-showing-key-outcomes-of-interest.-UMEC/VI (62.5/25-micrograms)-was-compared-to-other-dual-and-mono-therapies.-The-outcomes-of-interest-include-mean-difference-in-change-from-baseline-in-trough-FEV1-at-weeks-12-and-24,-mean-difference-in-change-from-baseline-in-SGRQ-total-score-at-week-24,-mean-difference-in-change-from-baseline-in-TDI-focal-score-at-week-24-and-mean-difference-in-rescue-medication-use-at-week-24

SGRQ: Mean difference in CFB in SGRQ total score at week 24

Methodology and networks of evidence1

icon-showing-an-image-of-lungs

A systematic literature review (SLR) identified RCTs in adults aged ≥40 years with COPD that compared LAMA, LABA or LAMA/LABA as monotherapy or in combination with ICS with any LAMA/LABA dual therapy (fixed-dose or open combination)

icon-showing-a-piece-of-paper-with-a-list-and-the-number-8,000-plus-at-the-bottom-of-the-page-in-an-orange-box

The SLR of published studies performed up to 19 Nov 2020 included 8171 initially identified abstracts. The SLR was based on a previously published SLR that identified publications up until October 2015

icon-showing-a-piece-of-paper-with-49-studies-written-on-it

NMA informed by 49 clinical studies:

44 reported trough FEV1 data at 12 weeks

22 reported trough FEV1 at 24 weeks

  • Click here to learn about methodological considerations

    • All analyses were conducted using a frequentist weighted regression based approach.1
    • Both fixed effects (FE) and random effects (RE) models were used and in the absence of heterogeneity results from both models were identical. RE models automatically accounted for heterogeneity when present.1
    • The similarity assumption (i.e. comparison of baseline characteristics) and consistency assumption (tested through heterogeneity statistics such as I2, Q-statistic and corresponding p-value) were deemed to hold, indicating that the transitivity assumption also holds.1

    FE, fixed effect; RE, random effect.

  • Click here for more information on all the trials included in the NMA¹

    Author, year Study name/NCT number Link
     
    Dual versus dual therapy
    		 
    Kerwin, 20172 A2349, NCT02487446 Link
    Kerwin, 20172
    A2350, NCT02487498
    		Link
    Feldman, 20173 GSK 204990, NCT02799784 Link
    Kalberg, 20164 GSK 116961, NCT02257385 Link
    Vogelmeier, 20165 AFFIRM COPD, NCT01908140 Link
    Wedzicha, 20165
    FLAME, NCT01782326
    		Link
    Maltais, 20196
    AERISTO, NCT03162055
    		Link
    Buhl, 20157 QUANTIFY, NCT01120717 Link
    Frith, 20188
    FLASH, NCT02516592
    		Link
    Singh, 20159
    DB2116134, NCT01822899
    		Link
    Donohue, 201510
    DB2114930, NCT01817764
    		Link
    Donohue, 201510 DB2114951, NCT01879410 Link
    Vogelmeier, 201311 ILLUMINATE NCT01315249 Link
    Zhong, 201512 LANTERN, NCT01709903 Link
    Hoshino, 201513 NR Link
      Dual versus monotherapy  
    Lipworth, 201814 PINNACLE-4, NCT02343458 Link
    Singh, 201515 OTEMTO 1, NCT01964352 Link
    Singh, 201515 OTEMTO 2, NCT02006732 Link
    Vogelmeier, 200816 NCT00134979 Link
    Maleki-Yazdi, 201417 ZEP117115, NCT01777334 Link
    Calverley, 201818 DYNAGITO, NCT02296138 Link
    Maltais, 201919 EMAX, NCT03034915 Link
    Mahler, 201220 INTRUST-1, NCT00846586 Link
    Mahler, 201220 INTRUST-2, NCT00877383 Link
    Vincken, 201421 GLOW6, NCT01604278 Link
    Wedzicha, 201322 SPARK, NCT01120691 Link
    Decramer, 201423 DB2113374, NCT01316913 Link
    Decramer, 201423 DB2113360, NCT01316900 Link
    Donohue, 201324 DB2113373, NCT01313650 Link
    Sethi, 201925 AMPLIFY, NCT02796677 Link
    D'Urzo, 201426 AUGMENT COPD, NCT01437397 Link
    D'Urzo, 201727a AUGMENT EXTENSION, NCT01572792 Link
    Mahler, 201528 FLIGHT1, NCT01727141 Link
    Mahler, 201528 FLIGHT2, NCT01712516 Link
    Ferguson, 201629 FLIGHT3, NCT01682863 Link
    Kerwin, 201730 DB2116960, NCT01899742 Link
    Donohue, 201631 NCT01437540 Link
    Martinez, 201732 PINNACLE-1, NCT01854645 Link
    Martinez, 201732 PINNACLE-2, NCT01854658 Link
    Bateman, 201333 NCT01202188 Link
    Tashkin, 200934 NR Link
    Celli, 201435 NCT01313637 Link
    Singh, 201436 ACLIFORM-COPD, NCT01462942 Link
    ZuWallack, 201437 ANHELTO 1, NCT01694771 Link
    ZuWallack, 201437 ANHELTO 2, NCT01696058 Link
    Buhl, 201538 TONADO 1, NCT01431274 Link
    Buhl, 201538 TONADO 2, NCT01431287 Link
      Dual versus PBO  
    Riley, 201839 GSK 201317, NCT02275052 Link
    Siler, 201640 201211, NCT02152605 Link
    Dahl, 201341 ENLIGHTEN, NCT01120717 Link

aThe extension trial AUGMENT EXTENSION was not counted as a unique trial but secondary publication to main trial. NR, not reported; PBO, placebo.

PREV
NEXT

Network of evidence informed by 44 clinical studies reporting trough FEV1 at 12 weeks1

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-FEV1-analysis-at-12-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010.

Network of evidence informed by 22 clinical studies reporting trough FEV1 at 24 weeks1

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-FEV1-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010.

Network of evidence informed by 17 clinical studies reporting SGRQ total score at 24 weeks1

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-SGRQ-total-score-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010.

Network of evidence informed by 14 clinical studies reporting TDI focal score at 24 weeks1

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-TDI-focal-score-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010.

Network of evidence informed by 14 clinical studies reporting rescue medication use at 24 weeks1

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-rescue-medication-use-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010.

PREV
NEXT

Lung function: UMEC/VI versus dual therapy comparators at 12 weeks1

Mean difference in CFB in trough FEV1 of UMEC/VI versus dual therapy comparators at 12 weeks

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-trough-FEV1-of-UMEC/VI-(62.5/25)-versus-dual-therapy-comparators-at-12-weeks

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010. Frequentist NMA FE model.

Lung function: UMEC/VI versus dual therapy comparators at 24 weeks1

Mean difference in CFB in trough FEV1 of UMEC/VI versus dual therapy comparators at 24 weeks

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-trough-FEV1-of-UMEC/VI-(62.5/25)-versus-dual-therapy-comparators-at-24-weeks

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010. Frequentist NMA FE model.

Lung function: UMEC/VI versus monotherapy comparators at 12 weeks1

Mean difference in CFB in trough FEV1 of UMEC/VI versus monotherapy comparators at 12 weeks

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-trough-FEV1-of-UMEC/VI-(62.5/25)-versus-monotherapy-comparators-at-12-weeks

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010. Online ahead of print. Frequentist NMA FE model.

Lung function: UMEC/VI versus monotherapy comparators at 24 weeks1

Mean difference in CFB in trough FEV1 of UMEC/VI versus monotherapy comparators at 24 weeks

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-trough-FEV1-of-UMEC/VI-(62.5/25)-versus-monotherapy-comparators-at-24-weeks

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:4961-5010. Online ahead of print. Frequentist NMA FE model.

Mean difference in CFB in SGRQ total score of UMEC/VI versus comparators at 24 weeks1

Comparator

CFB (95% CI)

p-value

ACL/FOR 400/6

0.19 (–1.18, 2.20)

 0.8509

ACL/FOR 400/12

–0.42 (–2.06, 1.22)

 0.6170

GLY/FOR 18/9.6

–0.55 (–2.02, 0.92)

0.4615
IND/GLY 110/50

1.00 (–0.23, 2.24)

 0.1108
TIO 18 + FOR 12

–0.36 (–2.80, 2.07)

0.7716
UMEC 62.5

0.04 (–1.04, 1.11)

0.9474

UMEC 125

–1.89 (–3.49, –0.30)

 0.0196
ACL 400

–1.04 (–2.77, 0.69)

 0.2373

GLY 18

 –2.12 (–3.61, –0.62) 0.0056

GLY 50

 –1.43 (–2.67, –0.18)

0.0245

TIO 18

–1.37 (–2.42, –0.32)

0.0105
VI 25

–0.44 (–1.75, 0.86)

0.5055

FOR 9.6

 –0.86 (–2.35, 0.64)

0.2613
FOR 10

–0.41 (–2.85, 2.02)

0.7410

FOR 12

–1.27 (–3.06, 0.52)

 0.1638

SAL 50

 –1.79 (–3.04, 0.52) 0.0049

IND 150

–1.01 (–3.52, 1.50)

0.4310
PBO

–3.30 (–4.50, –2.10)

 ≤0.0001

 

The full publication is available here: https://pubmed.ncbi.nlm.nih.gov/35857184/

Mean difference in CFB in TDI focal score of UMEC/VI versus comparators at 24 weeks1

Comparator

CFB (95% CI)

p-value
ACL/FOR 400/6

–0.19 (–0.57, 0.20)

0.3414

ACL/FOR 400/12

 –0.22 (–0.58, 0.14) 0.2355

GLY/FOR 18/9.6

0.33 (0.13, 0.52)

 0.0013

IND/GLY 110/50

–0.18 (–0.51, 0.15)

 0.2908

TIO 18 + FOR 12

0.20 (–0.34, 0.75)

0.4639

UMEC 62.5

 0.32 (0.08, 0.57)

0.0090
UMEC 125

0.55 (0.16, 0.93)

 0.0053

ACL 400

0.18 (–0.21, 0.57)

0.3570
GLY 18

0.68 (0.32, 1.04)

0.0003
GLY 50 0.06 (–0.29, 0.41)

0.7386

TIO 18

 0.34 (0.03, 0.64)

0.0310

VI 25

0.42 (0.13, 0.71)

0.0045

FOR 9.6

 0.48 (0.11, 0.84) 0.0104

FOR 12

0.22 (–0.17, 0.61)

 0.2605

SAL 50

0.43 (0.14, 0.72)

0.0040

IND 150

0.11 (–0.23, 0.45)

 0.5259
PBO

1.08 (0.82, 1.35)

≤0.0001

The full publication is available here: https://pubmed.ncbi.nlm.nih.gov/35857184/

Mean difference in CFB in rescue medication use of UMEC/VI versus comparators at 24 weeks1

Comparator CFB (95% CI)) p-value
ACL/FOR 400/6 –0.17 (–0.46, 0.12
 0.2444
ACL/FOR 400/12 –0.46 (–0.66, –0.25) ≤0.0001
GLY/FOR 18/9.6 –0.09 (–0.29, 0.12) 0.4041
IND/GLY 110/50 –0.20 (–0.58, 0.18) 0.3094
UMEC 62.5 –0.33 (–0.48, –0.18) ≤0.0001
UMEC 125 –0.36 (–0.72, –0.01) 0.0461
ACL 400 –0.37 (–0.61, –0.12) 0.0040
GLY 18 –0.58 (–0.80, –0.37) ≤0.0001
GLY 50 –0.86 (–1.24, –0.48) ≤0.0001
TIO 18 –0.50 (–0.51, –0.49) ≤0.0001
VI 25 –0.29 (–0.64, 0.06) 0.1041
FOR 9.6 –0.27 (–0.49, –0.06) 0.0109
FOR 12 –0.27 (–0.53, 0.00) 0.0466
SAL 50 –0.28 (–0.43, –0.13) 0.0002
IND 150 –0.51 (–0.89, –0.13) 0.0088
PBO –1.16 (–1.33, –0.98) ≤0.0001

The full publication is available here: https://pubmed.ncbi.nlm.nih.gov/35857184/

Network meta-analysis (NMA)

Comparing efficacy of dual therapies among patients with COPD

LEARN MORE

Summary

Summary of NMA class comparison results for UMEC/VI versus dual and mono-broncodilator therapies

LEARN MORE

Abbreviations

ACL, aclidinium; CFB, change from baseline; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FE, fixed effects; FEV1, forced expiratory volume in 1 second; FOR, formoterol; GLY, glycopyrronium bromide; ICS, inhaled corticosteroids; IND, indacaterol; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; NMA, network meta-analysis; NR, not reported; OLO, olodaterol; PBO, placebo; QD, once daily; RCT, randomised controlled trial; SAL, salmeterol; SGRQ, St George’s Respiratory Questionnaire; SLR, systematic literature review; TDI, transition dyspnoea index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

References

  1. Ismaila AS, et al. Adv Ther.2022;39:4961-5010.
  2. Kerwin E, et al. Lung. 2017;195:739-747.
  3. Feldman GJ, et al. Adv Ther. 2017;34:2518-2533.
  4. Kalberg C, et al. Drugs R D. 2016;16:217-227.
  5. Wedzicha JA, et al. N Engl J Med. 2016;374:2222-2234.
  6. Maltais F, et al. Adv Ther. 2019;36:2434-2449.
  7. Buhl R, et al. Thorax. 2015;70:311-319.
  8. Frith PA, et al. Respirology. 2018;23:1152-1159.
  9. Singh D, et al. BMC Pulm Med. 2015;15:91.
  10. Donohue JF, et al. Respir Med. 2015;109:870-881.
  11. Vogelmeier CF, et al. Lancet Respir Med. 2013;1:51-60.
  12. Zhong N, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:1015-1026.
  13. Hoshino M, et al. Pulm Pharmacol Ther. 2015;30:128-133.
  14. Lipworth BJ, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2969-2984.
  15. Singh D, et al. Respir Med. 2015;109:1312-1319.
  16. Vogelmeier C, et al. Respir Med. 2008;102:1511-1520.
  17. Maleki-Yazdi MR, et al. Respir Med. 2014;108:1752-1760.
  18. Calverley PMA, et al. Lancet Respir Med. 2018;6:337-344.
  19. Maltais F, et al. Respir Res. 2019;20:238.
  20. Mahler DA, et al. Thorax. 2012;67:781-788.
  21. Vincken W, et al. Int J Chron Obstruct Pulmon Dis. 2014;9:215-228.
  22. Wedzicha JA, et al. Lancet Respir Med. 2013;1:199-209.
  23. Decramer M, et al. Lancet Respir Med. 2014;2:472-486.
  24. Donohue JF, et al. Respir Med. 2013;107:1538-1546.
  25. Sethi S, et al. Int J Chron Obstruct Pulmon Dis. 2019;14:667-682.
  26. D'Urzo AD, et al. Respir Res. 2014;15:123.
  27. D'Urzo A, et al. Respir Med. 2017;125:39-48.
  28. Mahler DA, et al. Am J Respir Crit Care Med. 2015;192:1068-1079.
  29. Ferguson GT, et al. Chronic Obstr Pulm Dis. 2016;3:716-728.
  30. Kerwin EM, et al. Int J Chron Obstruct Pulmon Dis. 2017;12:745-755.
  31. Donohue JF, et al. Respir Med. 2016;116:41-48.
  32. Martinez FJ, et al. Chest. 2017;151:340-357.
  33. Bateman ED, et al. Eur Respir J. 2013;42:1484-1494.
  34. Tashkin DP, et al. COPD. 2009;6:17-25.
  35. Celli B, et al. Chest. 2014;145:981-991.
  36. Singh D, et al. BMC Pulm Med. 2014;14:178.
  37. ZuWallack R, et al. Int J Chron Obstruct Pulmon Dis. 2014;9:1133-1144.
  38. Buhl R, et al. Eur Respir J. 2015;45:969-979.
  39. Riley JH, et al. ERJ Open Res. 2018;4:00073-2017.
  40. Siler TM, et al. Int J Chron Obstruct Pulmon Dis. 2016;11:971-979.
  41. Dahl R, et al. Respir Med. 2013;107:1558-1567.

© 2022 GSK group of companies or its licensor. Trademarks are owned by or licensed to the GSK group of companies.

NX-GBL-UCV-WCNT-220016 | Date of preparation: February 2023