Safety profiles similar for benralizumab, mepolizumab in severe eosinophilic asthma
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Key takeaways:
- Benralizumab induces depletion of eosinophils and mepolizumab reduces activation.
- The study followed patients for up to 5 years.
- The most common serious adverse events were related to asthma.
Mepolizumab and benralizumab had similar safety profiles for patients with severe eosinophilic asthma despite their different mechanisms, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
These findings also indicate that targeting eosinophils remains a safe strategy for treating these patients, Andrew Menzies-Gow, MD, global medical head, respiratory biologics, AstraZeneca, and colleagues wrote.
“Uncontrolled severe eosinophilic asthma has considerable disease burden, including poor symptom control, poor quality of life and morbidity,” Menzies-Gow told Healio. “So, it’s important that treating physicians and patients have options for treatment.”
Benralizumab (Fasenra, AstraZeneca) induces the direct, rapid and nearly complete depletion of eosinophils from the peripheral blood and lungs, whereas mepolizumab (Nucala, GSK) reduces their maturation, recruitment and activation, the researchers explained.
However, the researchers noted that eosinophils may help maintain homeostasis and protect the body from parasitic infections, prompting them to investigate the long-term safety of treatment that partially or nearly completely depletes them.
Study results
The study comprised 446 adults from the MELTEMI study and 347 patients aged 12 years and older from the COLUMBA study. The COLUMBA group (mean age, 52.2 years; 65% women; 92% white) received 100 mg of mepolizumab every 4 weeks.
In the MELTEMI group, 226 (mean age, 51.2 years; 63.7% women; 92.5% white) received 30 mg of benralizumab subcutaneously every 4 weeks (q4w) and 220 (mean age, 51.8 years; 63.6% women; 92.7% white) received it every 8 weeks (q8w).
Total drug exposures among the patients in the MELTEMI group with up to 5 years of enrollment included 784.28 patient-years for the q4w cohort and 797.03 for the q8w cohort, for 1,581.31 patient-years overall. The COLUMBA study had a total drug exposure of 1,201 patient-years for patients enrolled up to 4.5 years.
Mean times since diagnosis with asthma included 18.3 years (standard deviation [SD], 14.98 years) for the MELTIMI q8w group, 17.6 years (SD, 13.26 years) for the MELTIMI q4w group and 21.4 years (SD, 14.22 years) for the COLUMBA group.
“This side-by-side analysis of MELTEMI and COLUMBA reinforces the safety of targeting eosinophils as a treatment strategy for patients with severe eosinophilic asthma,” Menzies-Gow said.
Viral upper respiratory tract infections were the most common nonserious adverse events across all three groups, impacting 47.3% of the MELTIMI q4w group, 46.5% of the MELTIMI q8w group and 48.7% of the COLUMBA group.
These infections were most prevalent during the first year for the MELTIMI q8w group, affecting 22.1%, and during the second year for the MELTIMI q4w group, affecting 25.6%, with decreases during the third year and beyond for both groups.
Event rate findings were similar for both groups as well. Also, there were no parasitic infections for any of the patients in the MELTEMI or COLUMBA groups. Bronchitis and asthma, which were the next most common nonserious adverse events, had generally similar rates in the MELTEMI and COLUMBA groups.
Rates of headaches, which were the next most common nonserious adverse events, included 28.5% for the COLUMBA group, 13.3% for the MELTEMI q8w group and 20.9% for the MELTEMI q4w group.
Event rates for bronchitis, asthma and headaches generally decreased for both MELTEMI groups. Also, tachycardia was the most frequent nonserious cardiac adverse event in the MELTEMI groups, affecting 1.3% in the q8w cohort and 2.3% in the q4w cohort.
Percentages of five nonserious types of patient-reported adverse events were about twice as high in the COLUMBA group, compared with the MELTEMI groups.
Upper respiratory tract infection percentages included 23.3% for COLUMBA, 8% for MELTEMI q8w, and 12.3% for MELTEMI q4w. For back pain, percentages included 18.2% for COLUMBA, 7.1% for MELTEMI q8w and 7.3% for MELTEMI q4w.
Percentages of patients reporting arthralgia included 16.7% in COLUMBA, 6.6% for MELTEMI q8w and 6.4% for MELTEMI q4w. Extremity pain percentages included 2.7% for COLUMBA, 3.5% for MELTEMI q8w, and 2.7% for MELTEMI q4w.
Finally, respiratory tract infections affected 11% in the COLUMBA group, 2.7% in the MELTEMI q8w group and 1.8% in the MELTEMI q4w group.
Except for four reports of back pain, one report of a respiratory tract infection in the q8w group and one upper respiratory tract infection in the q4w group, there were no further adverse events after 3 years in the MELTEMI study.
Percentages of patients experiencing injection site reactions included 12.1% of the COLUMBA group, 4.5% of the MELTEMI q4w group and 2.2% of the MELTEMI q8w group. Event rates for injection site reactions included 107 per 1,000 patient-years for COLUMBA, 53.55 for the MELTEMI q4w group and 11.29 for the MELTEMI q8w group.
The MELTEMI q4w group’s second year had the highest year-by-year event rate at 106.3 per 1,000 patient-years, or 22 events involving seven patients. This fell to 39.94 per 1,000 patient-years in the third year, with six events among two patients.
“Asthma-related events were the leading type of severe eosinophilic asthma for both studies across all treatment groups,” Menzies-Gow said. “This result was not unexpected, given the challenge to control SEA in this patient population. It is also the basis for treating these patients with benralizumab and mepolizumab.”
Asthma-related serious adverse events affected 8.6% of the MELTEMI q4w group, 8% of the MELTEMI q8w group and 9.5% of the COLUMBA group. Most of the other serious adverse events across all three groups affected one to two patients.
Overall event rates for serious adverse events for the three groups were comparable, the researchers said, with 35.1 per 1,000 patient-years for the MELTEMI q8w group, 40.8 for the MELTEMI q4w group and 39 for the COLUMBA group.
Rates of asthma-related serious adverse events were consistent for the first 2 years before falling, with only one event after 3 years, among the MELTEMI q8w group. These rates saw a gradual decline from the first to the second year with no serious asthma events reported after the third year in the MELTEMI q4w group.
The highest year-by-year asthma serious adverse event rates were highest in the third year for the MELTEMI q8w group at 41.47 per 1,000 patient-years and 45.6 per 1,000 patient-years for the MELTEMI q4w group.
Pneumonia was the second most common serious adverse event, reported by six patients in COLUMBA and two patients in the MELTEMI q8w group. None of the patients in the MELTEMI q4w group reported any pneumonia.
Additionally, none of the patients in any group reported any major cardiac adverse events.
Malignancies included one case of basal cell carcinoma, papillary thyroid cancer, prostate cancer and transitional cell carcinoma each in the MELTEMI q8w group; two cases of basal cell carcinoma and one case each of adenocarcinoma and transitional cell carcinoma in the MELTEMI q4w group; and three cases of basal cell carcinoma, two cases of prostate cancer and one case of breast cancer in COLUMBA.
Conclusions, next steps
These findings indicated comparable long-term safety and tolerability for benralizumab and mepolizumab for patients with severe eosinophilic asthma, the researchers said, reinforcing the safety of targeting eosinophils as a treatment strategy, adding that near-complete depletion does not increase risks compared with partial reductions.
“These findings align with what I have seen in practice,” Menzies-Gow added.
Along with these safety signals, Menzies-Gow continued, these biologics also reduced oral corticosteroid use among these patients.
“However, questions remained regarding potential differences in safety between partial versus near-complete eosinophil reductions, respectively,” he said.
Further studies should continue to evaluate the long-term safety of these biologics, the researchers said.
Menzies-Gow further noted the growing consensus across the scientific community to review asthma management targets with innovations in patient care and treatments including biologics, which he said could change the trajectory of severe asthma care.
Perspective
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These findings are significant, given that we hypothesize that there are biologic benefits of near complete eosinophilic depletion with benralizumab, but it was previously unknown if that posed a higher risk for adverse effects compared with partial reduction with mepolizumab. This is particularly important in light of the recently documented inhaled steroid-sparing effects of benralizumab.
Also, these findings are consistent with our anecdotal experience in clinic of an overall low adverse effect profile with both benralizumab and mepolizumab. These findings additionally can allow providers to communicate to their that biologics overall have favorable safety profiles with low occurrences of related to the biologics.
The next step in this research should be continued long-term follow-up and comparison with dupilumab and other biologics from a safety and efficacy perspective. Long-term studies should include a set of core efficacy outcomes, such as those determined via a stakeholder Delphi consensus, and adverse effect outcomes.
Reference:
Tejwani V, et al. Ann Allergy Asthma Immunol. 2021;doi:10.1016/j.anai.2021.03.022.
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