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Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation

2020; Elsevier BV; Volume: 100; Linguagem: Inglês

10.1016/j.cct.2020.106228

1559-2030

Wanda Phipatanakul, David T. Mauger, Theresa W. Guilbert, Leonard B. Bacharier, Sandy Durrani, Daniel J. Jackson, Fernando D. Martínez, Anne M. Fitzpatrick, Amparito Cunningham, Susan J. Kunselman, Lisa M. Wheatley, Cindy S. Bauer, Carla M. Davis, Bob Geng, Kirsten M. Kloepfer, Craig Lapin, Andrew H. Liu, Jacqueline A. Pongracic, Stephen J. Teach, James F. Chmiel, Jonathan M. Gaffin, Matthew Greenhawt, Meera Gupta, Peggy S. Lai, Robert F. Lemanske, Wayne J. Morgan, William J. Sheehan, Jeffrey R. Stokes, Peter S. Thorne, Hans C. Oettgen, Elliot Israel, Lisa Bartnikas, David B. Kantor, Perdita Permaul, Nicole Akar-Ghibril, Mehtap Haktanir-Abul, Sigfus Gunnalaugsson, Brittany Esty, Elena Crestani, Michelle C. Maciag, Marissa Hauptman, Sachin N. Baxi, Elizabeth Burke‐Roberts, Margee Louisias, Tina Banzon, Saddiq B. Habiballah, Alan A. Nguyen, Tregony Simoneau, Samantha Minnicozzi, Elsa Treffeisen, Brenna LaBere, Mia T. Chandler, Manoussa Fanny, Anna Cristina Vasquez-Muniz, Vanessa Konzelman, Giselle Fernández García, Sullivan Waskosky, Anna Ramsey, Ethan Ansel-Kelly, Elizabeth M. Fitzpatrick, Vaia Bairaktaris, Jesse Fernandez, Brianna Hollister, Owen Lewis, Masai McIntosh, Sigrid Almeida, Carolyn M. Kercsmar, Karen M. McDowell, Cassie Shipp, Stephanie Ward, N.Y.-W. Lin, Alisha George, Ryne Simpson, I. St. Onge, Will Corwin, Grant Geigle, Alisha Hartmann, J. J. Broderick, Stanley J. Szefler, Naomi Miyazawa, Brooke Tippin, Darci Anderson, Sonya Belimezova, Nidhya Navanandan, Tanya Watson, Michelle Olson, Wanda Caldwell, Caroline C. Horner, Lila Kertz, Tina Norris, Katherine Rivera‐Spoljaric, Jeffrey R. Stokes, Andrea M. Coverstone, Molly McDowell, Sarah Laughlin, Gina Laury, Rosanne Donato, Elizabeth Beckett-Firmage, Elia A. Cornidez, Silvia Hortencia Hernández López, Michèle Simon, Raymond Skeps, Monica M. Vasquez, Rob Gage, Heather L. Shearer, Melissa Pecak, Sandi Winters, Christine Rukasin, Bernadette McNally, D Johnson, Brian P. Vickery, Jocelyn R. Grunwell, Morgan Nicholls, Taqwa El-Hussein, Shilpa J. Patel, D.K. Pillai, Melanie Makhija, Rachel G. Robison, Jennifer Bosworth, Michelle Catalano, Kathleen Cassin, Laura Bamaca DeLeon, Nicole Titus, Sydney Leibel, Seema S. Aceves, Diba Mortazavi, Lauren Loop, Sara Anvari, Aikaterini Anagnostou, Kathy Pitts, Sopar Sebutra, Daisy Tran, Chivon McMullen-Jackson, Jay Jin, Nadia Krupp, Clement L. Ren, Girish Vitalpur, Lori Shively, Patrick Campbell, L. Bendy, Patrick Campbell, Lisa France, Sylvia Jara, Sarah B. Cichy, Linda Engle, Aimee Merchlinski, Melanie Payton, Pam Ramsey, James Schmidt, Dan Tekely, Angela Updegrave, Rachel Weber, Ronald Zimmerman, Peter S. Thorne, Nervana Metwali, Xuefang Jing, Melissa Walker, Steven S. Sigelman, Ling Li, Sanaz Hamrah,

Pharmaceutical studies and practices

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.