Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics

Mohsen Sadatsafavi; Trung N Tran; Ghislaine Scelo; Ming-Ju Tsai; John Busby; Benjamin Emmanuel; Liam G Heaney; Christine Jenkins; Flavia Hoyte; Giorgio Walter Canonica; Rohit Katial; Enrico Heffler; Eileen Wang; Francesca Puggioni; Michael E Wechsler; Ledit R F Ardusso; Jorge Máspero; Martin Sivori; Cathy Emmas; Andrew N Menzies-Gow; Neda Stjepanovic; Sinthia Z Bosnic-Anticevich; Belinda Cochrane; Eve Denton; Peter G Gibson; Mark Hew; Peter G Middleton; Matthew J Peters; Guy G Brusselle; Renaud Louis; Florence Schleich; George C Christoff; Todor A Popov; Celine Bergeron; Mohit Bhutani; Kenneth R Chapman; Andréanne Côté; Simon Couillard; Delbert R Dorscheid; Libardo Jiménez-Maldonado; Ivan Solarte; Carlos A Torres-Duque; Susanne Hansen; Celeste M Porsbjerg; Charlotte Suppli Ulrik; Alan Altraja; Arnaud Bourdin; Konstantinos P Exarchos; Athena Gogali; Konstantinos Kostikas; Michael P Makris; Andriana I Papaioannou; Patrick D Mitchell; Takashi Iwanaga; Tatsuya Nagano; Yuji Tohda; Mona S Al-Ahmad; Désirée Larenas-Linnemann; Bernt Bøgvald Aarli; Piotr Kuna; Cláudia Chaves Loureiro; Riyad Al-Lehebi; Adeeb A Bulkhi; Wenjia Chen; Yah Ru Juang; Mariko Siyue Koh; Anqi Liu; Chin Kook Rhee; Borja G Cosio; Luis Perez-de-Llano; Diahn-Warng Perng; Chau-Chyun Sheu; Hao-Chien Wang; Bassam Mahboub; Laila Salameh; David J Jackson; Pujan H Patel; Paul E Pfeffer; Njira Lugogo; Roy Alton Pleasants; Aaron Beastall; Lakmini Bulathsinhala; Victoria Carter; Nevaashni Eleangovan; Kirsty Fletton; John Townend; Ruth B Murray; David B Price

Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics

Mohsen Sadatsafavi, Trung N Tran, Ghislaine Scelo, Ming-Ju Tsai, John Busby, Benjamin Emmanuel, Liam G Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Walter Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael E Wechsler, Ledit R F Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew N Menzies-GowNeda Stjepanovic, Sinthia Z Bosnic-Anticevich, Belinda Cochrane, Eve Denton, Peter G Gibson, Mark Hew, Peter G Middleton, Matthew J Peters, Guy G Brusselle, Renaud Louis, Florence Schleich, George C Christoff, Todor A Popov, Celine Bergeron, Mohit Bhutani, Kenneth R Chapman, Andréanne Côté, Simon Couillard, Delbert R Dorscheid, Libardo Jiménez-Maldonado, Ivan Solarte, Carlos A Torres-Duque, Susanne Hansen, Celeste M Porsbjerg, Charlotte Suppli Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos P Exarchos, Athena Gogali, Konstantinos Kostikas, Michael P Makris, Andriana I Papaioannou, Patrick D Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona S Al-Ahmad, Désirée Larenas-Linnemann, Bernt Bøgvald Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al-Lehebi, Adeeb A Bulkhi, Wenjia Chen, Yah Ru Juang, Mariko Siyue Koh, Anqi Liu, Chin Kook Rhee, Borja G Cosio, Luis Perez-de-Llano, Diahn-Warng Perng, Chau-Chyun Sheu, Hao-Chien Wang, Bassam Mahboub, Laila Salameh, David J Jackson, Pujan H Patel, Paul E Pfeffer, Njira Lugogo, Roy Alton Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth B Murray, David B Price

Abstract

Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

Originalsprog	Engelsk
Tidsskrift	American Journal of Respiratory and Critical Care Medicine
ISSN	1073-449X
Status	E-pub ahead of print - 18 maj 2025

Citationsformater

Sadatsafavi, M., Tran, T. N., Scelo, G., Tsai, M.-J., Busby, J., Emmanuel, B., Heaney, L. G., Jenkins, C., Hoyte, F., Canonica, G. W., Katial, R., Heffler, E., Wang, E., Puggioni, F., Wechsler, M. E., Ardusso, L. R. F., Máspero, J., Sivori, M., Emmas, C., ... Price, D. B. (2025). Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics. American Journal of Respiratory and Critical Care Medicine. Advance online publication.

Sadatsafavi, M, Tran, TN, Scelo, G, Tsai, M-J, Busby, J, Emmanuel, B, Heaney, LG, Jenkins, C, Hoyte, F, Canonica, GW, Katial, R, Heffler, E, Wang, E, Puggioni, F, Wechsler, ME, Ardusso, LRF, Máspero, J, Sivori, M, Emmas, C, Menzies-Gow, AN, Stjepanovic, N, Bosnic-Anticevich, SZ, Cochrane, B, Denton, E, Gibson, PG, Hew, M, Middleton, PG, Peters, MJ, Brusselle, GG, Louis, R, Schleich, F, Christoff, GC, Popov, TA, Bergeron, C, Bhutani, M, Chapman, KR, Côté, A, Couillard, S, Dorscheid, DR, Jiménez-Maldonado, L, Solarte, I, Torres-Duque, CA, Hansen, S , Porsbjerg, CM , Ulrik, CS, Altraja, A, Bourdin, A, Exarchos, KP, Gogali, A, Kostikas, K, Makris, MP, Papaioannou, AI, Mitchell, PD, Iwanaga, T, Nagano, T, Tohda, Y, Al-Ahmad, MS, Larenas-Linnemann, D, Aarli, BB, Kuna, P, Chaves Loureiro, C, Al-Lehebi, R, Bulkhi, AA, Chen, W, Juang, YR, Koh, MS, Liu, A, Rhee, CK, Cosio, BG, Perez-de-Llano, L, Perng, D-W, Sheu, C-C, Wang, H-C, Mahboub, B, Salameh, L, Jackson, DJ, Patel, PH, Pfeffer, PE, Lugogo, N, Pleasants, RA, Beastall, A, Bulathsinhala, L, Carter, V, Eleangovan, N, Fletton, K, Townend, J, Murray, RB & Price, DB 2025, 'Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics', American Journal of Respiratory and Critical Care Medicine.

@article{14c9c975cc064146b76941c4319eee30,

title = "Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics",

abstract = "Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.",

author = "Mohsen Sadatsafavi and Tran, {Trung N} and Ghislaine Scelo and Ming-Ju Tsai and John Busby and Benjamin Emmanuel and Heaney, {Liam G} and Christine Jenkins and Flavia Hoyte and Canonica, {Giorgio Walter} and Rohit Katial and Enrico Heffler and Eileen Wang and Francesca Puggioni and Wechsler, {Michael E} and Ardusso, {Ledit R F} and Jorge M{\'a}spero and Martin Sivori and Cathy Emmas and Menzies-Gow, {Andrew N} and Neda Stjepanovic and Bosnic-Anticevich, {Sinthia Z} and Belinda Cochrane and Eve Denton and Gibson, {Peter G} and Mark Hew and Middleton, {Peter G} and Peters, {Matthew J} and Brusselle, {Guy G} and Renaud Louis and Florence Schleich and Christoff, {George C} and Popov, {Todor A} and Celine Bergeron and Mohit Bhutani and Chapman, {Kenneth R} and Andr{\'e}anne C{\^o}t{\'e} and Simon Couillard and Dorscheid, {Delbert R} and Libardo Jim{\'e}nez-Maldonado and Ivan Solarte and Torres-Duque, {Carlos A} and Susanne Hansen and Porsbjerg, {Celeste M} and Ulrik, {Charlotte Suppli} and Alan Altraja and Arnaud Bourdin and Exarchos, {Konstantinos P} and Athena Gogali and Konstantinos Kostikas and Makris, {Michael P} and Papaioannou, {Andriana I} and Mitchell, {Patrick D} and Takashi Iwanaga and Tatsuya Nagano and Yuji Tohda and Al-Ahmad, {Mona S} and D{\'e}sir{\'e}e Larenas-Linnemann and Aarli, {Bernt B{\o}gvald} and Piotr Kuna and {Chaves Loureiro}, Cl{\'a}udia and Riyad Al-Lehebi and Bulkhi, {Adeeb A} and Wenjia Chen and Juang, {Yah Ru} and Koh, {Mariko Siyue} and Anqi Liu and Rhee, {Chin Kook} and Cosio, {Borja G} and Luis Perez-de-Llano and Diahn-Warng Perng and Chau-Chyun Sheu and Hao-Chien Wang and Bassam Mahboub and Laila Salameh and Jackson, {David J} and Patel, {Pujan H} and Pfeffer, {Paul E} and Njira Lugogo and Pleasants, {Roy Alton} and Aaron Beastall and Lakmini Bulathsinhala and Victoria Carter and Nevaashni Eleangovan and Kirsty Fletton and John Townend and Murray, {Ruth B} and Price, {David B}",

year = "2025",

month = may,

day = "18",

language = "English",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

}

TY - JOUR

T1 - Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics

AU - Sadatsafavi, Mohsen

AU - Tran, Trung N

AU - Scelo, Ghislaine

AU - Tsai, Ming-Ju

AU - Busby, John

AU - Emmanuel, Benjamin

AU - Heaney, Liam G

AU - Jenkins, Christine

AU - Hoyte, Flavia

AU - Canonica, Giorgio Walter

AU - Katial, Rohit

AU - Heffler, Enrico

AU - Wang, Eileen

AU - Puggioni, Francesca

AU - Wechsler, Michael E

AU - Ardusso, Ledit R F

AU - Máspero, Jorge

AU - Sivori, Martin

AU - Emmas, Cathy

AU - Menzies-Gow, Andrew N

AU - Stjepanovic, Neda

AU - Bosnic-Anticevich, Sinthia Z

AU - Cochrane, Belinda

AU - Denton, Eve

AU - Gibson, Peter G

AU - Hew, Mark

AU - Middleton, Peter G

AU - Peters, Matthew J

AU - Brusselle, Guy G

AU - Louis, Renaud

AU - Schleich, Florence

AU - Christoff, George C

AU - Popov, Todor A

AU - Bergeron, Celine

AU - Bhutani, Mohit

AU - Chapman, Kenneth R

AU - Côté, Andréanne

AU - Couillard, Simon

AU - Dorscheid, Delbert R

AU - Jiménez-Maldonado, Libardo

AU - Solarte, Ivan

AU - Torres-Duque, Carlos A

AU - Hansen, Susanne

AU - Porsbjerg, Celeste M

AU - Ulrik, Charlotte Suppli

AU - Altraja, Alan

AU - Bourdin, Arnaud

AU - Exarchos, Konstantinos P

AU - Gogali, Athena

AU - Kostikas, Konstantinos

AU - Makris, Michael P

AU - Papaioannou, Andriana I

AU - Mitchell, Patrick D

AU - Iwanaga, Takashi

AU - Nagano, Tatsuya

AU - Tohda, Yuji

AU - Al-Ahmad, Mona S

AU - Larenas-Linnemann, Désirée

AU - Aarli, Bernt Bøgvald

AU - Kuna, Piotr

AU - Chaves Loureiro, Cláudia

AU - Al-Lehebi, Riyad

AU - Bulkhi, Adeeb A

AU - Chen, Wenjia

AU - Juang, Yah Ru

AU - Koh, Mariko Siyue

AU - Liu, Anqi

AU - Rhee, Chin Kook

AU - Cosio, Borja G

AU - Perez-de-Llano, Luis

AU - Perng, Diahn-Warng

AU - Sheu, Chau-Chyun

AU - Wang, Hao-Chien

AU - Mahboub, Bassam

AU - Salameh, Laila

AU - Jackson, David J

AU - Patel, Pujan H

AU - Pfeffer, Paul E

AU - Lugogo, Njira

AU - Pleasants, Roy Alton

AU - Beastall, Aaron

AU - Bulathsinhala, Lakmini

AU - Carter, Victoria

AU - Eleangovan, Nevaashni

AU - Fletton, Kirsty

AU - Townend, John

AU - Murray, Ruth B

AU - Price, David B

PY - 2025/5/18

Y1 - 2025/5/18

N2 - Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

AB - Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

M3 - Journal article

C2 - 40383109

SN - 1073-449X

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

ER -

Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics

Abstract

Fingeraftryk

Citationsformater