Asthma

Biologic switching in severe asthma: is the first choice usually the best?


Low rates of switching between biologics for severe asthma suggest clinicians are selecting appropriate and effective agents for their patients – but could there also be an element of under-switching?

A study of 3,531 adult patients from 11 countries with at least two biologics available found 79% remain on their first biologic for at least six months.

Not surprisingly given it was first to market in most jurisdictions, omalizumab was the most common agent (88%) for those first starting biologics in 2015. But by 2019, benralizumab was the most common agent (29.6%), then mepolizumab (24.5%) and dupilumab (23.1%).

The study found that in patients who switched, the most common first switch was from omalizumab to an anti–IL-5/5R (49.6%; n=187/377). The second most common switch was within class, adding or switching from one anti–IL-5/5R to another (30.8%; n=116/377).

For the few patients who switched more than once, the most common subsequent biologic switch was from one anti–IL-5/5R to another (44.4%; n=20/45).

The study found patients who switched biologics were more likely to have higher eosinophils, a history of more exacerbations and used more healthcare resources including ED visits and hospital stays.

“These factors may be associated with biologic switching simply because such patients are likely to qualify for more than one drug, eg subjects commencing omalizumab who are known to have a high BEC will have the option to switch to anti–IL-5/5R therapy, and within the eosinophilic phenotype, there is scope to switch between different anti–IL-5/5R agents,” it said.

By far the most common reason for switching a biologic was due to insufficient clinical efficacy (86.3%).

The study said the low percentage of patients who switched to another biologic suggested “appropriate biomarker-guided biologic selection and good clinical efficacy of the initial biologic”.

However a substantial proportion of patients qualify for more than one biologic agents and response to an untried alternative agent was clearly unknown, the study said.

“These findings naturally trigger the question: “Is the first biologic prescribed to a patient usually the best one for that individual, or are we under-switching?”

The investigators suggested there may be an element of settling for conservative response thresholds such as a 50% reduction in exacerbation rate rather than trying for something higher.

There was also a natural reluctance to take on the logistical hurdles, time and effort involved in switching to another biologic.

Australian perspective

Co-investigator Professor John Upham, from the University of Queensland Diamantina Institute and PA-Southside Clinical Unit, told the limbic that while there was no local data in the study, most Australian clinicians would think the findings ring true.

“Probably 80% of people do very well on the biologics for asthma and then you get a group of people either where it doesn’t work and then a small group of people who have side effects who need to get switched.”

“But in the people who get switched, it’s usually due to lack of efficacy or not improving in the way that you’d hoped. That’s the most common reason for switching.”

Professor Upham said clinicians are sometimes faced with tricky situations where a patient on a biologic only improves slightly.

“They’re not brilliant but they are a bit better and then the question is do you try another agent when they might get better or they might get worse? That’s a dilemma for patients and prescribing doctors.”

He said regulations around switching – or trying to switch back after a potentially unsuccessful switch – do make people hesitant to switch.

“I think people are starting to get a little bit braver about switching than they used to be but I think it’s very reasonable to say that there are a group of people who maybe would benefit from switching but the clinician or the patient is a bit nervous about going down that pathway.”

He said that to fulfil the requirements of the PBS, clinicians have to demonstrate a certain level of improvement in the Asthma Control Questionnaire.

While the Questionnaire was fine for ticking boxes, he said he likes to have a more in-depth discussion with patients about whether they were happy with their level of improvement.

“ I think it’s something that is best done as a shared decision – talking to the patient about the pros and cons, getting their view and trying to get an accurate assessment of how well they have done is pretty important. Sometimes you get a richer  understanding of what’s going on rather than just looking at the score on its own.”

He said there was scope for more long term studies on people who switch.

“Do they go from one half-good treatment to another half-good treatment or do they dramatically improve? Once some of that long term data comes out that’ll make it a lot easier to make decisions around whether to switch or not.”

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