Biologics Reduce Severe Asthma Exacerbations in Real-world Study of Vulnerable Patients

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Real-world use of biologic agents for treatment of severe asthma (SA) is consistently associated with up to >50% reduction in disease exacerbations, according to findings from the ongoing CHRONICLE Study presented at the annual meeting of the American College of Chest Physicians (CHEST 2021), held in Orlando, Florida, and virtually between October 17-20, 2021.

The study focused specifically on groups of patients with SA whose response to biologic therapies has not been previously studied.

The advent of biologic therapeutics (monoclonal antibodies [mAbs]) that target specific inflammatory pathways has significantly enhanced treatment for the 5% to 10% of asthma patients with SA. CHRONICLE investigators, led by Reynold Panettieri, Jr, MD, vice chancellor for translational medicine and science and director of the Rutgers Institute for Translational Medicine and Science, were interested in the real-world effectiveness of mAbs in subgroups of SA patients who were not included in the original randomized clinical trials of the biologics. They included in that group those with pre-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥80%, comorbid COPD, or significant smoking history.

The noninterventional study is ongoing with the objective to examine use of biologics and outcomes among patient subgroups with SA who initiate mAb therapy in treatment with allergists/immunologists or pulmonologists. They also are interested in the effect on SA exacerbation of switching between biologics and switching from biologics to other agents for SA. 

Patients eligible for the study are adults aged ≥18 years with a diagnosis of SA who are receiving FDA-approved biologics and/or maintenance systemic corticosteroids, plus those uncontrolled on high-dose inhaled corticosteroids with additional controller medications.

Participating sites report asthma exacerbations and medications for 12 months prior to enrollment and every 6 months after enrollment. For participants initiating a biologic agent or who switch between 2 biologics, investigators calculated exacerbation rates 6 months before and after the initiation or the change.

RESULTS

For the period between February 2018 and February 2021 there were 2793 patients enrolled in CHRONICLE; at enrollment 66% (n=1832) were receiving biologics. During the study, researchers report that 2025 patients were using biologics at any point, with 1810 reporting ongoing use. Among those using biologic agents, 324 (16%) reported switching between agents.

Decline in exacerbation rates 6 months before/after biologic initiation

• Overall, patients starting biologics experienced a 58% reduction in exacerbations (from 1.80 to 0.76 per patient-year), with a greater reduction observed among those starting non–anti-IgE biologics (62%) vs anti-IgE agents (44%).

• Patients who switched biologics experienced a 49% reduction in exacerbations (1.47 vs 0.75 per person-year).
• Switching from anti-IgE therapy to anti–interleukin (IL)-5/IL-5R/IL-4R therapy was associated with greater reduction in exacerbations than was switching among anti–IL-5/IL-5R/IL-4R therapies (58% vs 46%, respectively).
• Reductions in exacerbation rates were significant in patients who had pre-biologic FEV₁ <80% and those with FEV₁ ≥80% (66% and 54%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with/without a COPD diagnosis (58% and 52%, respectively).

Similar decline in exacerbation rates 12 months before/after biologic initiation

For all patients, the exacerbation rate declined by 70% after biologic initiation (from 1.72 to 0.5 per patient-year). Exacerbation rates were reduced in all subgroups and reductions were statistically significant (P<.0001) in patients with pre-biologic FEV₁< 80%, never smokers, current/former smokers, and patients without a COPD diagnosis.

In their summary points Pannetieri et al point out that the real-world results from CHRONICLE both validate and extend findings from randomized, placebo-controlled trials, providing data on patient groups with SA whose responses to biologic therapy have not been previously studied. The authors emphasize the significant reductions in exacerbations observed in patients who switched biologic therapies during the study, which they say highlights “the need for a personalized approach to biologic therapy and the value of switching if the response to a patient’s initial biologic treatment is suboptimal.”

Reference: Panettieri R, Lugogo N, Moore W, et al. Biologic medications for severe asthma are effective in the real-world, including in subgroups not studied in randomized trials: results from the CHRONICLE study. Chest. 2021;160 (supplement): A20-A25.