Published Online: October 27, 2015
Asthma exacerbations in children most frequently occur during the fall season when they return to school, a time referred to as the September Epidemic of Asthma. Given the risks inherent with exacerbations and the failure of current treatment to fully prevent these episodes, new and novel approaches are needed to reduce these events.
Stephen Teach and co-investigators describe their PROSE trial in a recently published article in The Journal of Allergy and Clinical Immunology (JACI). Teach et al designed PROSE (Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations) to determine if a targeted strategy of beginning preventative therapy with omalizumab 4 to 6 weeks before the start of school and continuing it for the next four months would be more efficacious than (1) placebo or (2) a boost of ICS, in preventing fall asthma exacerbations among children already receiving guidelines-based therapy for their asthma.
Over two fall cycles in 2012 and 2013, 727 participants were recruited, aged 6 to 17 years old, who resided in a low-income census tract in predefined inner-city areas. Study interventions were added to ongoing guideline-based treatment beginning 4 to 6 weeks prior to the beginning of school and ending 90 days after the start of school.
The key outcomes were as follows: first, the odds of participants at all treatment levels having at least one exacerbation were significantly lower in the omalizumab vs. placebo arm (11.3% vs. 21.0%, OR=0.48; 95% CI 0.25-0.92). A non-statistically significant difference was found between omalizumab and the ICS booster (8.4% vs 11.1%, OR=0.73; 95% CI 0.33-1.64). If, however, the participant had experienced an exacerbation during the run-in phase, omalizumab was strikingly more efficacious than placebo, (6.4% vs. 36.3%, OR=0.12; 05% CI 0.02-0.64). In addition, in the group with an exacerbation during the run-in, omalizumab was also more efficacious than an ICS boost (2.0% vs. 27.8%, OR=0.05; 95% CI 0.003-0.98). Finally, in a subset of participants, peripheral blood mononuclear cells (PBMC) were obtained to determine the effect of omalizumab on dendritic cell generation of interferon-α, an anti-viral agent. Omalizumab significantly enhanced, or restored, interferon-α generation, during an in vitro incubation with rhinovirus.
The observations by Teach et al, indicate that seasonal directed treatment with omalizumab reduces fall exacerbations in a high-risk group of allergic asthma subjects, and this preventative effect is particularly efficacious in those who had experienced a recent exacerbation. Increasing inhaled steroid treatment levels above those recommended by the EPR-3 guidelines to achieve control offers little to no benefit in preventing exacerbations. Finally, a reduction in circulating and cell-bound IgE was associated with a restoration of anti-viral interferon-α generation. The authors’ findings demonstrate that an exacerbation identifies a group at high risk for exacerbations in the subsequent year and suggest that the targeting of directed treatment to times of the year of greatest risk can be highly efficacious and, as a consequence, limit treatment duration.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.