Mepolizumab reduces need for corticosteroids among patients with severe asthma
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Mepolizumab reduced the need for maintenance oral corticosteroids and systemic corticosteroid bursts among patients with severe asthma, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
The monoclonal antibody also was well tolerated by patients as it provided disease control, Charles Pilette, MD, professor with the department of pulmonary medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium, and colleagues wrote in the study.
The REALITI-A prospective, observational cohort study involved 84 centers across Europe and North America and included 822 patients (63% female; mean age, 54 years; standard deviation [SD], 13.6). Mean asthma duration totaled 19.7 years, and geometric mean baseline blood eosinophil count totaled 353 cells/µL.
The researchers further reported that 319 (39%) of these patients had used maintenance oral corticosteroids (mOCS) at baseline and that these patients began mepolizumab (Nucala, GSK) treatment predominantly to reduce their OCS burden.
Treatment results
After a year of treatment, 80% of patients on mepolizumab continued to use it, with a mean proportion of possible treatment days covered of 87.6% (SD, 15.15%). Lack of efficacy (6%) and patient decision (4%) were the most common reasons for discontinuing treatment.
At baseline, the median mOCS dose was 10 mg per day (interquartile range [IQR], 5-15). This decreased to 2.5 mg per day (IQR, 0-5) during weeks 53 to 56, which equaled a 75% reduction.
When stratified into baseline mOCS doses, those taking less than 10 mg per day saw doses decrease during weeks 53 to 56 from a median of 5 mg per day to 0.4 mg per day, or a reduction of 92%. Patients taking 10 mg or more per day saw a decrease from a median of 12.9 mg per day to 5 mg per day, or a 61% reduction, during the same time period.
The proportion of patients discontinuing daily mOCS treatment increased from 29% during weeks 25 to 28 to 43% during weeks 53 to 56. Also, 64% reported a 50% or greater reduction in mOCS dose from baseline.
Specifically, 49% of patients taking less than 10 mg per day and 36% of patients taking 10 mg or more per day at baseline discontinued daily mOCS use during weeks 53 to 56. Also, 60% of the former group and 69% of the latter group experienced a 50% or greater reduction in use since baseline.
Exacerbation decreases
Researchers assessed the impact of treatment on the use of systemic corticosteroid bursts — defined as OCS usage for at least 3 days or a single parental systemic corticosteroid administration for worsening asthma symptoms — by assessing the rate of clinically significant exacerbations (CSEs), or deterioration in symptom control requiring systemic corticosteroid bursts with or without an ED visit or hospital admission.
The researchers called the 71% decrease in CSEs between the pretreatment and 1-year follow-up periods significant (P < .001). This reduction occurred regardless of baseline mOCS use. Patients taking less than 10 mg per day of mOCS at baseline saw greater improvements than those taking higher doses.
Compared with the treatment period, patients had greater odds for experiencing no CSEs during the follow-up period (OR = 13.2; 95% CI, 10-17.4), which persisted in analyses of patients taking less than 10 mg per day at baseline (OR = 19.2; 95% CI, 9.4-39.2) and those taking 10 mg or more per day (OR = 6.2; 95% CI, 3.6-10.4).
These reductions in CSEs indicated a reduced need for systemic corticosteroid bursts, the researchers wrote. Higher and cumulative systemic corticosteroid doses have been associated with higher rates of infections and cardiovascular, gastrointestinal and metabolic disorders.
The researchers further found reductions in rates of exacerbations requiring hospitalization or an ED visit (RR = 0.24; 95% CI, 0.2-0.29) or hospitalization alone (RR = 0.31; 95% CI, 0.24-0.39) compared with the pretreatment period regardless of baseline mOCS use.
Follow-up period
Compared with the pretreatment period, there also was significantly less health care resource utilization related to asthma such as rates of hospitalization (RR = 0.47; 95% CI, 0.37-0.58), and ED (RR = 0.42; 95% CI, 0.33-0.53) and outpatient visits (RR = 0.43; 95% CI, 0.37-0.51) during the follow-up period, the researchers found.
Asthma Control Questionnaire-5 score improvements over baseline between baseline and month 3 were clinically significant (least squares mean change, –1.21; 95% CI, –1.32 to –1.1), and these improvements were sustained through month 12 (least squares mean change, –1.23; 95% CI, –1.38 to –1.08). Work Productivity and Impairment scores improved by month 12 as well, according to the researchers.
Among the safety population (n = 823), treatment-related adverse events occurred in 85 patients (10%) during follow-up, with six patients (< 1%) experiencing serious adverse events. One patient died of a diffuse liver malignancy and hepatic cancer that the researchers considered related to the mepolizumab treatment.
Mepolizumab can substantially safely reduce OCS burden for patients with severe asthma while improving symptom control, the researchers concluded, adding that physicians should consider initiating its treatment among these patients.
Perspective
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Andrew M. Namen, MD, FCCP, FAASM
The use of steroid therapy for asthma is associated with a number of complications, including the development of elevated blood sugars, diabetes, bone loss, osteoporosis, glaucoma, high blood pressure and neuropathy. Anytime you’re stuck between the possibility of not breathing and the risk for these complications, you weigh treatment decisions very closely.
This study specifically looked at people with eosinophilic asthma. These patients respond favorably to steroids as maintenance therapy, which helps their asthma get under better control. As a monoclonal and IL-5 antibody, mepolizumab reduces eosinophilic inflammation, which is why it is being investigated as an alternative.
This significant study mirrored what many of us who have been using this medication have experienced. Mepolizumab has been associated with getting patients off steroids or reducing their overall daily steroid does. But this represents the largest prospective cohort of eosinophilic asthmatics in which the changes in the study mirrored what you hope to see in practice.
Its results compared very well with what I see in practice, where patients have a reduced number of exacerbations with mepolizumab. In fact, its cohort of patients were very sick compared with other smaller studies. These patients had a higher mean eosinophil count on presentation and longer periods of having asthma. Also, a significant proportion of patients had prior or active tobacco use. These patient features mirror my practice.
However, about 92% of the population in the study was Caucasian, which is a little different from my group. But it was a multicenter multinational prospective cohort, which is representative of a good design. It also used at least 12 months of historical information, with results based on these data vs. what happened during the 56-week observed study period. It found a reduction from four exacerbations a year, which is significant and means a sick population, to less than two or about 1.5.
Another interesting finding was who benefitted from mepolizumab more when the cohort was separated into those patients who used 10 mg or more a day of OCS and those who used less than 10 mg a day. The patients who used less than 10 mg a day saw greater reductions in the number of exacerbations and in steroid use compared with those with dosages greater than 10 mg a day, which really occurred toward the tail end of week 29 and continued into week 56.
That was surprising, because you would think that if someone was on a higher dose of steroids, mepolizumab would have a greater impact. Maybe as the study continues into its second year, we will see similar reductions among the patients taking higher OCS doses.
This also tells us as providers not to wait until someone is on 10 mg of OCS a day to try mepolizumab. You might want to consider mepolizumab earlier when your patients are still on lower daily maintenance doses and experiencing exacerbations.
Also, quality-of-life scores all showed signs of improvement before there was any clinically significant data showing symptom improvement. OCS and exacerbation reductions all were trending down nicely by about 25 weeks, but then really came down between 52 and 56 weeks, which is significant for each of those two groups.
Most patients exhibited quality-of-life improvements by 3 months that were sustained through 12 months. That’s the kind of result you like to see. You don’t want to see a person getting worse with longer therapy. You like to see that the improvement starts and is maintained or continues to improve.
Patients do not like being on OCS for the long term. Their need to breathe is sometimes outweighed by the long-term OCS side effects, in which they can feel weak and run down, and their attitude changes. When they come off OCS, or use OCS less, and don’t have to go to the hospital, they feel a whole lot better about their life in general. That’s what appears to have occurred in this group under mepolizumab, which mimics practice. They didn’t have to go to the hospital as often. They didn’t have to go to the ED. Their overall health and attitudes were better.
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Pilette C, et al. J Allergy Clin Immunol Pract. 2022;doi:10.1016/j.jaip.2022.05.042.
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