Real-World Study Backs Mepolizumab in Rhinosinusitis With Nasal Polyps

Mepolizumab (Nucala) improved outcomes for adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and put about one in five on the way to remission, a real-life study from Italy showed.

The nasal polyp score dropped from a median of 6 at baseline to 3 at 12 months on the 0-8 point scale (P<0.0001), with reductions that grew over time, reported researchers led by Eugenio De Corso, MD, PhD, of the University of Perugia, in Lancet Respiratory Medicine.

Health-related quality of life as measured by the sino-nasal outcome test-22 (SNOT-22; 0-110 point scale, with higher scores worse) gradually improved over 12 months from a median 59 at baseline to 21 at 12 months (P<0.0001).

“The progressive nature of improvement observed over time suggests that clinical benefits could continue to increase beyond the earlier phases of treatment,” the researchers wrote.

Disease control was achieved by 42% of patients at 12 months, and appeared likely to improve further as 20% of patients were on their way to remission (they met remission criteria but had not yet completed the 12-month duration required by its definition).

“Remission is now a recognized and achievable therapeutic goal in CRSwNP,” De Corso and team noted, but this might be the first time this measure has been reported with mepolizumab.

“Longer-term studies are needed to determine whether improvements in disease control and remission continue beyond 12 months or plateau thereafter,” they wrote. Even so, “these findings contribute to the currently limited real-world evidence on the 12-month effectiveness of mepolizumab in severe CRSwNP, offering novel insights for clinical decision-making,” they concluded.

In the phase III SYNAPSE trial that led to mepolizumab’s indication in CRSwNP, the median change in nasal polyp score from baseline to 12 months was 1 point with the anti-interleukin-5 monoclonal antibody compared with 0 in the placebo group. Nearly 22% of patients had at least a 3-point improvement in that score.

Prior real-world studies have affirmed benefit but largely involved single-center cohorts or small sample sizes, “failing to reflect the heterogeneity of the broader CRSwNP patient population in real life,” De Corso and colleagues noted.

This phase IV study included 621 consecutive patients across 25 Italian tertiary referral rhinology clinics experienced in the management of severe, uncontrolled CRSwNP and biologic therapies. Eligible patients started mepolizumab 100 mg every 4 weeks, and had not received any other biologic therapy within the prior 3 months.

Median age was 59 years, 57% were men, 52% had comorbid asthma, and 29% had non-steroidal anti-inflammatory drug-exacerbated respiratory disease. Among the 18% of patients who received prior biologic therapy before switching to mepolizumab, 57% had received dupilumab (Dupixent). While 20% had never undergone surgery for their rhinosinusitis, 38% had one prior surgery, 22% had undergone two, and 19% had undergone at least three.

In terms of secondary endpoints, all major symptoms and olfaction improved. However, 38% of patients with data on olfaction remained unable to smell at 12 months.

Comorbid asthma was associated with greater or more rapid improvements in SNOT-22 scores and self-reported symptoms. Patients with no prior biologic treatment had greater improvements in SNOT-22 scores compared with bio-experienced patients. “This finding could be related to the greater clinical complexity typically observed in patients switching from other biological therapies who did not respond adequately to the previous biological therapy,” the researchers suggested.

While there are no validated biomarkers for predicting mepolizumab response, the study linked better baseline olfactory function with higher likelihood of achievement of disease control across all timepoints, while less severe baseline nasal polyp score significantly predicted progression towards remission at 12 months. Asthma and baseline blood eosinophil count did not predict control or remission.

Limitations included the potential for some degree of selection bias inherent to observational real-world studies and an inability to attribute the effects specifically to mepolizumab due to lack of a control group. Also, “caution is warranted when generalizing these findings to non-European patients, as the study population was exclusively Italian,” De Corso and team noted.