New Insights from an Additional Analysis of the MANDARA Study

Introduction

For people living with eosinophilic granulomatosis with polyangiitis (EGPA), oral glucocorticoids such as prednisone have long been a cornerstone of treatment. While effective in controlling inflammation, these medications can cause significant side effects over time — including bone loss, elevated blood pressure, diabetes, and muscle weakness.

Finding ways to reduce or even stop the use of prednisone, without losing control over the disease, is therefore an important goal in clinical care. A recent post hoc analysis from the MANDARA study provides new data on this topic.

What is the MANDARA study?

MANDARA is a phase 3, international, randomized study comparing the effectiveness of two biologic therapies — benralizumab and mepolizumab — in people with EGPA. Both medications work by targeting interleukin-5 (IL-5) or its receptor, a pathway known to drive eosinophilic inflammation.

The primary goal of the study was to assess whether benralizumab is non-inferior to mepolizumab — in other words, whether it works at least as well — in helping patients achieve remission while using a low dose of prednisone.

The results showed that 57.7% of patients treated with benralizumab and 56.5% of those treated with mepolizumab met this remission goal, confirming that the two therapies are similarly effective at reducing disease activity while tapering prednisone to a low maintenance dose.

What did the additional analysis look at?

In addition to the primary results, researchers conducted a post hoc analysis using a more stringent definition of remission. In this version, remission was only counted if patients had no disease activity, had completely discontinued prednisone, and experienced no relapse during the 52-week study period.

This more demanding measure reflects a treatment outcome that is rarely achieved in clinical practice, but highly desirable: full disease control without ongoing steroid use.

Key findings

• 23.5% of patients in the benralizumab group achieved full remission without prednisone.
• In the mepolizumab group, this was 11.1%.
• Most patients who reached this level of remission did so within the first 36 weeks.
• Stopping prednisone did not lead to increased relapse rates.
• Patients who started the study on a lower prednisone dose and with lower disease activity had a higher likelihood of success.

These results suggest that benralizumab, under the right conditions, may offer a greater chance of achieving steroid-free remission in EGPA.

What does this mean for patients?

For some patients with EGPA, treatment with an IL-5 inhibitor may help achieve complete disease control without the need for long-term prednisone. This is relevant because many patients experience side effects from steroids — especially when used over months or years.

The findings from this analysis offer hope that, with close supervision and appropriate treatment choices, steroid tapering or even full discontinuation may be possible in selected patients.

Important considerations

• This was a post hoc analysis, meaning the outcomes were explored after the main study had concluded. As such, the findings are considered exploratory and not definitive.
• The study included patients with mild to moderate EGPA. The results may not apply to patients with severe organ-threatening disease.
• Tapering off prednisone should always be done gradually and under the guidance of a healthcare provider
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Conclusion

This additional analysis from the MANDARA study shows that steroid-free remission is possible for a subset of patients with EGPA. Biologic therapies such as benralizumab and mepolizumab can support this goal, with benralizumab showing somewhat better outcomes in this specific context. Further research is needed to better understand which patients are most likely to benefit and how these results can be safely translated into clinical practice.