Lower Dose Nucala Safe, Effective in EGPA With Fewer Adverse Events

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by Steve Bryson PhD |

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A lower, 100 mg dose of Nucala (mepolizumab) is equally effective at treating eosinophilic granulomatosis with polyangiitis (EGPA) as the standard 300 mg dose, and leads to less frequent adverse events, or AEs, a large European study showed.

These findings suggest that a lower monthly dose of Nucala could be acceptable for people with this form of ANCA-associated vasculitis, though randomized clinical trials should be conducted to confirm the benefits, the researchers said.

“At all time-points, AEs were more frequent among patients receiving mepolizumab 300mg/4 weeks” than the 100 mg dose, the investigators wrote.

“Around one fifth of patients reported AEs, and the 100mg/4 weeks dosage appeared associated with a lower rate of AEs,” they added.

The study, “Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European multicenter observational study,” was published in the journal Arthritis & Rheumatology.

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Nucala is approved in the U.S. and used off-label in Europe for the treatment of EGPA, an inflammatory disease that affects those with a history of asthma and/or allergies. It is currently prescribed at a dose of 300 mg, administered through under-the-skin injections (subcutaneously) every four weeks or about once per month.

Small recent studies have reported that a lower dose of Nucala — 100 mg every four weeks — could successfully control respiratory symptoms in EGPA patients. However, the benefits and adverse events (side effects) of 100 mg versus 300 mg of Nucala as a treatment for EGPA have never been compared.

Now, researchers based at the University of Florence, in Italy, decided to do just that.

“This study aimed to investigate the effectiveness and safety of [Nucala] 100 vs 300 mg/4 weeks in a large European cohort of patients with EGPA,” the team wrote.

The medical records of 203 eligible patients from eight countries, with a median age of 55.1 at the time of treatment initiation, were examined. All had been treated with Nucala between 2015 and 2020. Most were female (57.1%) and their median disease duration was 4.8 years.

At the start of treatment with Nucala, 92.1% of the patients had active disease, as determined by a Birmingham Vasculitis Activity Score (BVAS) above 0. Before Nucala, almost all (95.6%) had been receiving a stable regime of glucocorticoids (prednisone) in the previous three months, and 95% were taking inhaled therapy for asthma. Additional therapies included methotrexate, azathioprine, rituximab, or intravenous (into-the-vein) immunoglobulins.

A total of 168 patients received Nucala at a dose of 100 mg every four weeks, and 35 received the higher 300 mg monthly dose. During the follow-up period, 10 switched from 100 mg to 300 mg due to a lack of efficacy, while two switched from 300 mg to 100 mg for personal reasons. The remaining patients maintained a stable dose regimen for the entire follow-up.

After three months of Nucala, 25 patients (12.3%) had achieved a complete response to treatment — meaning no signs of disease activity (BVAS of 0), plus a corticosteroid dose of 4 mg/day or less. An additional 64 (31.5%) reached a partial response, defined as no disease activity plus a corticosteroid dose more than 4 mg/day.

Complete remission rates increased at 23.6% at six months, 30.4% after one year, and 35.7% at two years.

Of note, complete responses after three months were similar between patients on 100 mg or 300 mg of Nucala (12.0% vs. 18.2%), as were partial response outcomes (32.9% vs. 36.4%). Complete responses rates with both doses similarly increased at six months and one year.

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After two years, data were available for 39 patients on the 100 mg dose and 12 patients on 300 mg. More patients receiving 300 mg had a complete response (58.3% vs. 33.3%) or a partial response (33.3% vs. 30.8%), but the difference was not statistically significant, most likely due to the small number of 300 mg participants (just 12 individuals). Also, there was a non-significant higher response rate among those without ANCA antibodies, especially at two years.

Although 31.0% of patients who reached a complete response relapsed after a median time of six months, the relapse rates and time to relapse were similar between the two doses. For the 10 participants who switched from a lower to a higher dose, there was no clear benefit.

After three months of 100 mg Nucala monthly, there was a significant reduction in all active disease manifestations, which was maintained during follow-up. For those taking 300 mg, there was a significant reduction in pulmonary and ear, nose, and throat symptoms at all time points. In contrast, no apparent effect was observed on other non-respiratory symptoms.

Systemic disease activity also was reduced during follow-up for both doses. The median BVAS overall decreased from 4 at baseline to 2 at three months and further to a median of 0 at the other time points. Similarly, both doses were associated with a significant decline in daily glucocorticoid doses, with a significant number of patients discontinuing their glucocorticoid treatment. A reduction in other medications also was observed.

Overall, adverse events were experienced by 21.7% of patients, but were more common in those receiving the highest dose. Six patients required hospitalization due to adverse events, which included respiratory tract infections, stroke, heart inflammation, and adrenal insufficiency.

“In conclusion, this large European real-world study shows that [Nucala] is associated with an effective control of … EGPA manifestations, with a good safety profile,” the investigators wrote.

“Our data also suggest that [Nucala] 100mg/4 weeks could be an acceptable dosage for EGPA patients, and a valid alternative to the dosage licensed for this therapeutic indication,” they added.