Long-term omalizumab treatment provides continued benefit for patients with asthma
Patients with moderate-to-severe persistent allergic asthma on long-term omalizumab therapy had improved symptoms and reduced exacerbation risk with continued omalizumab use compared with those who discontinued use of the drug, according to the XPORT* trial.
The intent-to-treat population comprised 176 patients with persistent asthma who had a history of omalizumab exposure for approximately 5 years. Participants were randomized 1:1 to omalizumab continuation or withdrawal (switched to placebo) and were followed up every 4 weeks for 1 year. [J Allergy Clin Immunol 2017;140:162-169]
More than half of the participants in the omalizumab arm did not experience severe exacerbations compared with the withdrawal arm (67 percent vs 47.7 percent), translating to a significant reduction in exacerbation risk (adjusted odds ratio, 0.44, 95 percent confidence interval, 0.23–0.82).
The results from the withdrawal arm could also be suggestive of continued benefit in some patients, noted the researchers. “[T]hese subjects presumably, but not necessarily, experienced frequent exacerbations before starting omalizumab.”
Symptoms were better controlled with continued omalizumab therapy than withdrawal as evidenced by the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores (mean change from baseline to week 52, -1.16 vs -2.88; p=0.0188 and 0.22 vs 0.63; p=0.0039, respectively).
Additionally, participants in the withdrawal arm who experienced exacerbations had a higher peripheral eosinophil count at baseline (p<0.001) and increased FENO** values from baseline to week 12 (p=0.038) than those who did not have exacerbations.
Persistently high blood eosinophil counts while under omalizumab therapy may reflect a higher likelihood of exacerbations upon omalizumab withdrawal, while the increase in FENO values was considered a positive predictor of exacerbations, said the researchers. “[Both may] provide some insights for clinicians and might be useful biomarkers to guide treatment decisions.”
The lack of pretreatment exacerbation rates and ACT/ACQ scores might have limited the findings, noted the researchers, as these are essential for comparing postwithdrawal rates to accurately address a persistent benefit.
Overall, the findings suggest that patients will continue to benefit from ongoing omalizumab use after long-term therapy given the sustained benefit in terms of risk and impairment, according to the researchers.
However, the extent of a persistent effect after omalizumab withdrawal was not clearly elucidated, noted the researchers. “Had the study shown equal and extremely high or extremely low percentages of subjects in both arms without exacerbations, it would be easier to infer that omalizumab had a persistent effect or had lost its efficacy … Neither of these extremes was seen in this study.”