REALITI-A shows mepolizumab effectiveness in severe asthma
Preliminary real-world findings of the REALITI-A* study, presented at ERS 2019, have demonstrated a significant reduction in asthma exacerbations with mepolizumab, a result comparable to that of regulatory clinical trials with this drug.
Previous studies have demonstrated that mepolizumab is well tolerated and is associated with consistent reductions in exacerbations and oral corticosteroid (OCS) use in patients with severe eosinophilic asthma (SEA), said Professor Tim Harrison from the Nottingham NIHR Biomedical Research Centre, Nottingham City Hospital, Nottingham, UK, who presented the findings.
“However, in large numbers, data is lacking on the impact of mepolizumab in patients treated in routine clinical practice where patients are much more likely to be more heterogeneous and have other comorbidities,” he said.
“This 12-month initial analysis of the REALITI-A study, in patients with SEA who were early treatment initiators and receiving treatment in the real world, shows that mepolizumab is associated with significant reductions in the rate of exacerbations and … in maintenance OCS use,” he said.
The multinational (51 centres in seven countries) study population comprised 368 adults (mean age 53.1 years, 62 percent female, mean asthma duration 20 years) with SEA (mean blood eosinophil count 370 cells/μL) who were newly prescribed subcutaneous mepolizumab (100 mg).
Eighty-one and 83 percent of patients were on high-dose inhaled corticosteroids and additional asthma medications, respectively. Forty-eight percent of patients were on maintenance OCS at a median dose of 10 mg/day, and 19 percent of patients had previously received omalizumab for a mean 29.1 months.
Forty-three percent of patients were initiating mepolizumab to reduce exacerbations, while 28 and 20 percent were aiming to reduce OCS burden and asthma symptoms, respectively. A majority of patients (93 percent) had experienced a clinically significant exacerbation in the past 12 months (mean number of exacerbations, 4.7), defined as deterioration in asthma requiring use of systemic corticosteroids and/or hospital admission and/or emergency department (ED) visit.
Over 342.9 total patient-years of exposure and a median 13 mepolizumab administrations, there was a 69 percent reduction in the rate of clinically significant exacerbations/year following mepolizumab use compared with the 12 months prior (from a mean of 4.63 to 1.43 exacerbations/year; p<0.001). [ERS 2019, abstract OA2104]
The rate of exacerbations leading to hospitalization or ED visits was also reduced by 77 percent with mepolizumab (from a mean 1.14 to 0.27 exacerbations/year; p<0.001).
These findings were similar to those demonstrated in the MENSA** and MUSCA*** clinical trials which showed exacerbation rate reductions of 53 and 58 percent, respectively, with subcutaneous mepolizumab. [N Engl J Med 2014;371:1198-1207; Lancet Respir Med 2017;5:390-400]
However, the baseline exacerbation rates in the placebo groups in these trials were lower than that of REALITI-A (mean 1.74 [MENSA] and 1.21 [MUSCA] exacerbations/year vs 4.63 [REALITI-A]), noted Harrison.
In REALITI-A, mepolizumab was also associated with a 50 percent reduction in maintenance OCS use (from 10 to 5 mg/day) after 21–24 weeks that was sustained at 53–56 weeks. Thirty-four percent of patients who were on maintenance OCS at baseline were able to discontinue OCS by 12 months.
Fourteen percent of patients experienced adverse events (AEs), the most common of which was nervous system disorders (7 percent). Mepolizumab-related AEs led to permanent treatment discontinuation in nine patients. Two patients experienced severe AEs, with one incident each of hypersensitivity and pharyngeal swelling, with no fatalities.
“The safety profile of mepolizumab was similar to that observed in previous studies, with no new safety concerns,” said Harrison.