A fifth of patients no longer needed oral steroids 2 years after starting biologic
by Salynn Boyles
SAN ANTONIO — Treatment with the interleukin-5 (IL-5) antagonist mepolizumab (Nucala) increased freedom from oral corticosteroids after 2 years in patients with severe eosinophilic asthma, according to a post-hoc analysis of the real-world prospective REALITI-A trial.
The proportion of those achieving freedom from oral corticosteroids increased from 4% at week 0 to 22% at week 104 in the treated population of over 800 patients, and from 0% to 15% in those with baseline maintenance oral corticosteroid use, reported Peter Howarth, MD, BSc, DM, of GSK, during the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.
Howarth told MedPage Today that the sustained response to the biologic was particularly noteworthy given that the patients in the real-world trial tended to have very severe asthma.
“In this study, 39% of patients were on maintenance oral corticosteroids when they started mepolizumab and, despite high inhaled steroid use, they were averaging more than four exacerbations a year,” he said.
The data make a case for prescribing mepolizumab earlier in the disease course for patients with eosinophilic asthma, rather than as a last-resort drug, “before patients progress to very severe disease,” he added.
Other post-hoc analyses of REALITI-A presented at AAAAI examined outcomes among critical subgroups of patients with eosinophilic asthma, including those with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP), those with comorbid gastroesophageal reflux disease (GERD) or anxiety/depression, and those with overlapping allergic and eosinophilic endophenotypes.
Among 323 patients with severe eosinophilic asthma with comorbid CRSwNP, mepolizumab led to greater improvements at 2 years compared with patients without CRSwNP.
Compared with baseline, both groups experienced reductions in clinically significant exacerbations, with a rate ratio of 0.23 (95% CI 0.19-0.27) in patients with CRSwNP and 0.29 (95% CI 0.26-0.32) in patients without CRSwNP.
Asthma-related quality of life, measured by the Asthma Control Questionnaire-5 (ACQ-5), improved for both groups, but with greater improvements reported in the CRSwNP patients (mean score 2.72 vs 2.96).
Meanwhile, patients with comorbid GERD (n=309) or anxiety/depression (n=203) also saw reductions in clinically significant exacerbations after a year of treatment, but the reductions were not as great as those seen among patients without these conditions.
In addition, 39% of patients with GERD discontinued use of maintenance oral corticosteroids compared with 45% of patients without GERD, while 32% of those with anxiety/depression discontinued versus 46% of those without anxiety/depression.
Howarth pointed out that roughly three out of four patients with severe asthma have overlapping allergic and eosinophilic endophenotypes and are eligible for treatment with anti-eosinophilic biologics or anti-immunoglobulin E biologics, such as omalizumab (Xolair).
Among the 540 patients with overlapping allergic and eosinophilic endophenotypes, omalizumab-eligible versus -ineligible patients had higher geometric mean baseline blood eosinophil counts (352 vs 303 cells/mL) and higher geometric mean baseline total immunoglobulin E (213 vs 131 KU/L).
After a year on mepolizumab, median maintenance oral corticosteroid dose decreased versus baseline, regardless of omalizumab eligibility (eligible: 3.3 vs 10.0; ineligible: 1.9 vs 10.0).
The international REALITI-A trial included 822 adults with severe asthma and no prior use of mepolizumab before study enrollment across 84 treatment centers in Europe, Canada, and the U.S.
Mean age was 54, 63% were women, and mean asthma duration was 19.7 years.
Previous results showed that patients on a median 10-mg maintenance dose of oral corticosteroids at baseline reduced their intake to 2.5 mg at 1 year, while those on a median 5-mg maintenance dose at the start of the trial reduced their use to 0.4 mg.
Patients who were more likely to achieve oral corticosteroid freedom at 2 years included those with higher baseline blood eosinophil counts and those with slightly fewer clinically significant asthma exacerbations (mean 3.4 vs. 4.6) in the year prior to starting mepolizumab.