Real world data confirms benefits of biologics in severe asthma


By Mardi Chapman

3 Jul 2024

A/Prof. Eve Denton

An international research collaboration has confirmed the benefits of biologic therapies in a real world, severe asthma population of patients, most of whom did not meet standard eligibility criteria for RCTs.

While the LUMINANT study demonstrates that RCT findings can be largely extrapolated to a more heterogeneous group of asthma patients, about half of the patients on biologics had a suboptimal response.

The findings, published in the journal Allergy [link here], are a reminder that there are still unmet treatment needs in severe asthma.

The LUMINANT study comprised 8,451 eligible adults from the International Severe Asthma Registry (ISAR) representing five continents and 28 countries including Australia.

Patients who started on biologics (n=2,116) were younger, had an earlier age of onset of asthma and had a higher proportion of never smokers compared to the group who did not start biologics (n=6,635).

“Biologic initiators had significantly worse baseline asthma status than non-initiators across all outcome domains; however, mean biomarker concentrations (blood eosinophils, exhaled nitric oxide, and total IgE) did not differ significantly between the two groups,” the authors noted.

The study found higher response rates in patients who started on biologics compared to those who did not initiate biologics including a ≥50% reduction in annualised exacerbation rate (AER 59% v 44%), FEV1 improvement of ≥100 mL (54% v 34%), improved asthma control (49% v 42%) and long-term oral corticosteroid (LTOCS) dose reduction (49% v 28%).

Biologics initiators had super-responses in all outcome domains, with a higher proportion of super-responders in LTOCS reduction (39%), than in AER (32%), FEV1 (19%), or asthma control (30%).

Nevertheless, about 40–50% of initiators did not meet response criteria.

“The substantial proportion of non-responders, even among biologic initiators, highlights persisting unmet needs and challenges in treating patients with severe asthma,” the investigators said.

“Our findings raise several questions that warrant further investigation; for example, whether starting a biologic treatment earlier, before asthma has caused too much lung damage, might increase the ratio of responders/super-responders.”

In a subgroup analysis based on biologic class, patients who initiated anti-IL5/IL5Rs compared to anti-IgE initiators had worse baseline impairment but a greater improvement in AER (response, 62% vs. 52%, p < 0.001; super-response, 31% vs. 22%, p < 0.001).

“Anti-IL4/13 initiators had the highest proportions of responders in all domains, with 75% achieving improved asthma control and 58% new well-controlled asthma, although numbers for this group were small,” the study said.

First author on the paper Associate Professor Eve Denton, from the Alfred and St Vincent Hospital Melbourne, told the limbic the findings provided a broader perspective on the biologics compared to single biologic registries, single centre or single country studies.

“So it is quite reassuring with regards to the efficacy of biologics in a real world population that is quite diverse,” she said.

“I guess I would highlight that the cohort included mostly patients who were on either anti-IgE or anti-IL5/anti-IL5 receptors. A very small number of patients were on anti-IL4/13s but there were no patients in our cohort on anti-TSLPs, for example tezepelumab.”

She said it was possible that some of the patients in the study with suboptimal responses may not have yet been exposed to a biologic targeting the particular inflammatory pathway that was activated in their asthma.

“Tezepelumab is available elsewhere in the world but is not in Australia on the PBS at this stage. So there are more biologics on the horizon and perhaps they’ll be more effective for some people.”

Associate Professor Eve Denton said there was still a role for a multi-disciplinary, multi-dimensional assessment in patients with severe asthma, particularly those people that do not respond adequately to biologics.

“When you have a patient that responds as a super-responder to a biologic, that’s very satisfying, but I think this highlights that it’s a relatively small proportion that are achieving those really dramatic responses.”

“And so there’s still a role for multi-dimensional assessment where you’re assessing other factors, including comorbidities, but also lifestyle and behavioural factors like cigarette smoking, adherence to inhalers, weight loss and other medications.”

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