Should Jascayd (nerandomilast) be continued at the prescribed dose during an interstitial lung disease (ILD) flare?

Management of Jascayd (Nerandomilast) During ILD Flare

Continue Jascayd at the prescribed dose during an ILD flare, but the specific management depends critically on whether this represents progressive ILD versus rapidly progressive ILD (RP-ILD), as these require fundamentally different treatment approaches.

Understanding the Clinical Context

The term "ILD flare" is imprecise and requires clarification. Based on current guidelines and the drug's clinical trial data, you need to distinguish between:

Progressive ILD (Chronic Worsening)

• Decline in FVC ≥10% predicted, OR
• Decline in FVC 5-10% predicted PLUS worsening respiratory symptoms or increased fibrosis on HRCT
• Occurs over 24 months 1

Rapidly Progressive ILD (RP-ILD)

• Acute worsening or development of dyspnea typically <1 month duration
• New bilateral ground-glass opacity and/or consolidation on CT
• Deterioration not explained by cardiac failure or fluid overload 2

Management Algorithm

If This is Progressive ILD (Not Acute/Rapid):

Continue Jascayd without interruption. The FIBRONEER-ILD trial specifically enrolled patients with progressive pulmonary fibrosis and demonstrated that nerandomilast reduced FVC decline and improved survival over 15+ months of continuous treatment 2, 3.

• Nerandomilast showed hazard ratio of 0.51 for all-cause mortality compared to placebo 2
• Treatment effects were sustained throughout the trial period with mean exposure of 15.1 months 3
• The drug was specifically designed for and tested in patients with ongoing disease progression

Add or intensify immunosuppressive therapy based on the underlying autoimmune disease:

For autoimmune disease-related ILD progression (which represents the majority of Jascayd use cases given trial enrollment):

• Add mycophenolate, rituximab, cyclophosphamide, or nintedanib 1
• For IIM-ILD specifically: consider adding JAKi or calcineurin inhibitors 1
• For SSc-ILD, MCTD-ILD, or RA-ILD: consider tocilizumab 1
• Avoid long-term glucocorticoids (strongly recommended against in SSc-ILD, conditionally against in other SARD-ILD) 1, 4

If This is Rapidly Progressive ILD (Acute Exacerbation):

Continue Jascayd AND immediately add aggressive immunosuppression. The FIBRONEER-ILD trial excluded patients with acute ILD exacerbation within 3 months prior to enrollment 2, but this doesn't mean you should stop the drug—it means acute exacerbations require additional treatment.

Immediate management for RP-ILD:

1. Pulse IV methylprednisolone (conditionally recommended as first-line) 1
2. Add combination therapy - triple therapy for MDA-5 positive patients, double or triple therapy for others (conditionally recommended over monotherapy) 1
3. First-line RP-ILD options to add: rituximab, cyclophosphamide, IVIG, mycophenolate, CNI, or JAKi 1, 4
4. Early lung transplant referral if appropriate (conditionally recommended over later referral) 1

Do NOT add nintedanib or pirfenidone for RP-ILD - these are conditionally recommended against in this setting 1, 4

Key Clinical Considerations

Why Continue Jascayd?

1. Mechanism of action is complementary: Nerandomilast works via PDE4B inhibition to reduce inflammation and fibrosis through cAMP elevation 5, 6, which is mechanistically distinct from immunosuppressives
2. Trial data supports continuation: Patients in FIBRONEER-ILD who experienced events (including acute exacerbations) continued on study medication 2
3. Mortality benefit: The 49% reduction in all-cause mortality suggests ongoing benefit even during disease complications 2, 3

Safety During Acute Management

• Nerandomilast was well-tolerated with background immunosuppression in trials 7, 3
• Adverse events leading to discontinuation were only 12.3% for the 18mg BID dose over 15+ months 3
• No specific safety signals emerged during acute events in the trial population 2

Common Pitfall to Avoid

Do not stop Jascayd simply because the patient is worsening. Progressive disease was the indication for which this drug was studied and approved. The FIBRONEER trials specifically enrolled patients with documented progression 2. Stopping the drug removes a mechanistically distinct anti-inflammatory and antifibrotic agent at precisely the time when multi-pathway intervention is most needed.

Monitoring During Flare

While continuing Jascayd:

• Monitor for increased diarrhea (most common adverse effect, especially if adding nintedanib) 2
• Watch for weight loss and decreased appetite 2
• Consider dose reduction to 9mg BID only if tolerability becomes limiting (both doses showed similar efficacy) 2, 3

Special Population: Autoimmune ILD

For the 325 patients with autoimmune disease-related ILD in FIBRONEER-ILD, nerandomilast showed a hazard ratio of 0.56 for the composite endpoint of acute exacerbation, respiratory hospitalization, or death with the 18mg dose 7. This subgroup represents the most relevant population for your question, and continuation was standard practice in the trial.