Add-on reslizumab cuts exacerbations, OCS use in severe eosinophilic asthma

Reslizumab, a biologic targeting interleukin(IL)-5, reduced severe asthma exacerbation rate and oral corticosteroid (OCS) use in individuals with severe eosinophilic asthma, according to a real-world study using patient-level data from RAPSODI*.

“The beneficial effects were evident not only in patients receiving reslizumab as first add-on biologic therapy, but it also demonstrated additive efficacy … in those who previously failed another type 2 biologic and switched to reslizumab,” said the researchers.

Participants (n=134; mean age 53 years, 52 percent male) initiated reslizumab 0.3 mg/kg (4-weekly infusions) before April 2020 and had follow-up data for ≥6 months following initiation. They were classified as either initiators (biologic-naïve reslizumab initiators; n=56) or switchers (those who had switched from another type 2 biologic; n=78). [J Allergy Clin Immunol Pract 2022;10:2099-2108.e6]

In the overall population, reslizumab significantly reduced annualized exacerbation rate (AER; odds ratio [OR], 0.10; p<0.001) and daily median maintenance OCS dose (from 5 to 0 mg; p<0.001). These effects were similarly seen among initiators (p<0.001 [AER] and p=0.02 [OCS use]) and switchers (p<0.001 and p<0.01, respectively).

The fraction of OCS users also dropped substantially in the overall cohort (from 58 percent to 40 percent; OR, 0.20; p<0.001) and both subgroups (from 48 percent to 35 percent; OR, 0.11; p=0.09 [initiators], and from 65 percent to 43 percent; OR, 0.23; p=0.003 [switchers]).

“Remarkably, reslizumab treatment [in switchers] showed an additional improvement in the rate of exacerbations and OCS use … [This] suggests that reslizumab offered added value over previous type 2 biologics, including those targeting IL-5 in half of patients,” the researchers said.

 

Physicians’ insights

These findings were reinforced by an anonymized physician survey conducted to ascertain whether experts’ real-world clinical experience with reslizumab aligned with the results. The survey did show that asthma experts do recognize the additional benefit of reslizumab.

Although none of the 10 respondents prescribed reslizumab solely as first add-on treatment, 40 percent did so as second or third add-on biologic, while 60 percent prescribed reslizumab as both first and second or third add-on biologic. Almost all were satisfied/very satisfied with reslizumab; 80 percent found reslizumab to be of added value over other biologics.

“As a reason for prescribing reslizumab, 50 percent responded that they expected patients to respond better to reslizumab than to other type 2 biologics,” the researchers said.

 

Other notable points

Most participants had characteristics that differed from those of patients in phase III trials which, according to the researchers, might have precluded trial participation. “Despite these differences … the beneficial effects of reslizumab in the real world were largely comparable to those of the phase III trials. This suggests that in the real world, reslizumab is effective even if the strict inclusion criteria of phase III trials are not entirely met,” they said.

“Another noteworthy finding … is that patients prescribed reslizumab in the real world appeared to have more severe asthma than those included in phase III trials,” they continued. Indeed, most participants were at the extreme end of asthma severity and complexity (>50 percent were OCS-dependent and almost all had comorbidities), “yet only a minority of patients (14 percent) did not improve with this therapy.”

 

Implications

Patients with severe asthma typically have persistent symptoms that could impair daily living activities. [Lancet 2018;391:783-800; Eur Respir J 2017;50:1700765] “Moreover, these patients are at increased risk for severe, potentially fatal asthma exacerbations that can only be prevented often by frequent courses or continuous use of OCS, which are associated with serious long-term side effects,” said the researchers.

“The observed additional effect of reslizumab as second or third add-on treatment suggests that it may be worthwhile to switch patients who do not respond adequately to one specific type 2 biologic to a second add-on biologic, even if this second biologic targets the same molecular pathway,” they said.

Further studies shall ascertain whether greater drug potency, better dosing, pharmacodynamics or pharmacokinetics, or type of antibody or target drove the improved response in switchers, or whether it is merely an effect of longer-term inhibition of the inflammatory process in the airways with equally effective agents, they added.