Long-term outcomes improve in severe eosinophilic asthma with mepolizumab, benralizumab

Key takeaways:

• Annual exacerbation rates fell from 5.8 at baseline to 1.2 at 36 months.
• Quality-of-life questionnaire scores improved through 36 months.
• 29 patients were “super-responders” at 12 months.

Mepolizumab and benralizumab were associated with prolonged reductions in oral corticosteroid use among real-world patients with severe eosinophilic asthma, according to data in The Journal of Allergy and Clinical Immunology: In Practice.

These biologics also were associated with increased asthma control and improvements in asthma-associated quality of life, Fred Fyles, MBBS, junior clinical fellow in critical care at Liverpool University Hospitals, National Health Service Foundation Trust, and colleagues wrote.

The retrospective, single-center study comprised 81 patients (58% women; average age, 53.7 years) with severe eosinophilic asthma (SEA) who completed 36 months of treatment with mepolizumab (n = 56; Nucala, GSK) or benralizumab (n = 25; Fasenra, AstraZeneca).

All the patients were taking high doses of inhaled corticosteroids (ICS) when they began biologic therapy with average daily doses of 2,004 µg (standard deviation [SD], 395 µg) of beclomethasone propriate equivalents.

Also, all of the patients were using a concurrent long-acting beta agonist, 77 were using a long-acting muscarinic antagonist, 56 were using a leukotriene receptor antagonist and 54 were using all three.

Reduction in oral corticosteroids

Daily doses of maintenance oral corticosteroids (mOCS) across the entire cohort fell from 5.3 mg (SD, 6.9 mg) to 2.4 mg (SD, 4.3; P < .001) by 12 months and to 0.6 mg (SD, 1.9 mg; P < .001) at 36 months, with the decrease between 12 and 36 months also reaching significance (P < .001).

Proportions of patients who required daily mOCS fell from 60.5% (n = 49) at baseline to 32.1% (n = 26; P < .001) at 12 months and 11.1% (n = 9; P < .0001) at 36 months.

Also, 92% (n = 45) of the patients who needed mOCS at baseline had decreased corticosteroid requirements while on biologic therapy, with 82% (n = 40) experiencing complete mOCS cessation at 36 months.

The 49 patients mOCS using at the start of biologic treatment had an average daily dose of 8.8 mg (SD, 6.9 mg; range, 2.5-50 mg), which decreased to 3.8 (SD, 4.9; P < .0001) at 12 months and 1 mg (SD, 2.4; P < .0001) at 36 months.

These patients using mOCS at baseline also experienced improvements in annual exacerbation rates (AER) from 5.45 (SD, 3.3) at baseline to 0.9 (SD, 1.2; P < .0001) at 12 months and 1 (SD, 1.3; P < .0001) at 36 months.

Researchers observed significant improvements in Mini Asthma Quality of Life Questionnaire (mAQLQ) and Asthma Control Questionnaire-6 (ACQ-6) scores from baseline to 12 and 36 months for this group as well.

Other findings

In the total cohort, AER improved, from 5.8 (SD, 3) at baseline to 0.9 (SD = 1.2; P < .0001) at 12 months and 1.2 (SD, 1.5; P < .0001) at 36 months.

There were significant improvements across the full cohort in mAQLQ and ACQ-6 scores as well, the researchers found, with average changes from baseline to 12 and 36 months exceeding minimally important differences for both questionnaires.

Researchers observed modest improvements in FEV₁ and FEV₁ percent predicted across the cohort from baseline to 12 and 36 months, and fractional exhaled nitric oxide (FeNO) appeared to increase from baseline to those time points, but none of these results were statistically significant.

Eosinophil counts fell from baseline (0.52 mg/dL; SD, 0.45 mg/dL) to 12 months (0.06 mg/dL; SD, 0.09 mg/dL; P < .001) and 36 months (0.07 mg/dL; SD, 0.07 mg/dL; P < .001) as well.

The patients on benralizumab had complete eosinophil suppression at 36 months, with an average eosinophil count (EC) of 0 mg/dL. Fifteen of the 56 patients on mepolizumab achieved eosinophil suppression with a mean EC of 0.1 mg/dL.

There were no significant adverse events among the full cohort through 36 months as well, the researchers wrote, although there were 43 patients who began treatment but stopped before 36 months, including 28 who did so due to lack of efficacy.

‘Super-responders’

Also, 21 of the patients on mepolizumab (37.5%) and eight of the patients on benralizumab (32%) experienced a super-response to treatment at 12 months, including a reduction or cessation of all OCS and evidence of adequate asthma control, with improvements in FeNO and FEV₁.

These patients had significantly lower mOCS doses, lower AER and better mAQLQ and ACQ-6 scores at baseline than those patients who did not have a super-response, the researchers found.

At 36 months, 23 patients on mepolizumab (41%) and seven on benralizumab (28%) were super-responders, including 12 mepolizumab patients and two benralizumab patients who did not have a super-response at 12 months.

Based on these findings, the researchers said that mepolizumab and benralizumab led to significant and prolonged improvements in a range of clinical parameters, including reduced OCS use, increased asthma control, and improved asthma-related quality of life.