Doubt cast on LABA withdrawal in combination asthma therapy

By Caroline Price, Senior medwireNews Reporter

Researchers have urged doctors to be cautious over withdrawal of long-acting beta-2 agonist (LABA) therapy in patients with asthma controlled by this type of bronchodilator in combination with an inhaled corticosteroid (ICS), after finding the approach often results in destabilization of their condition.

Their meta-analysis of five available trials in patients aged 15 years or older found that a LABA step-off regimen led to increased asthma impairment, with worsening scores on asthma-related quality of life (QOL) and asthma control questionnaires, and fewer symptom-free days.

The findings run counter to a recent US Food and Drug Administration (FDA) labeling change for LABAs, which recommends stepping down LABA therapy once asthma control has been achieved and maintained, because of concerns over a higher risk of catastrophic asthma events with LABA therapy.

The study's authors emphasize that they found very few studies have properly assessed the effects of stepping off LABA use in patients with asthma controlled by combination ICS and LABA therapy. Until further evidence is available, they recommend physicians carefully weigh up the risks and benefits of LABAs for each individual patient.

In the five trials of LABA step-off compared with no change in use of a LABA and ICS combined that they identified, Thomas Casale (Creighton University, Omaha, Nebraska, USA) and team found the duration of controlled asthma before step-off was shorter than the minimum of 3 months currently recommended in asthma guidelines.

Pooled results showed the LABA step-off approach reduced the quality of life of patients by an average of 0.32 points on the Asthma Quality of Life Questionnaire, and reduced control of asthma by 0.24 points on the Asthma Control Questionnaire. LABA discontinuation also led to 9.15% fewer symptom-free days on average.

Indeed, patients in the step-off group were three times as likely as those staying on combination therapy to withdraw from their respective studies because of lack of efficacy or loss of asthma control.

The findings are published in the Archives of Internal Medicine. Writing in an accompanying editorial, Chee Chan and Andrew Shorr (Washington Hospital Center, DC, USA) say the FDA's failure to consider the patient-level impact of their labeling change ‑ which is placed as a black box warning ‑ is "worrisome."

"We hope that this meta-analysis helps to lift some of the black clouds in the debate surrounding LABAs. Similarly, physicians must now reevaluate the contents of the black box for LABAs, particularly in individuals whose asthma is well controlled with combination LABA and ICS therapy," they write.

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