How do Jascayd (nerandomilast) and Ofev (nintedanib) compare for treatment of idiopathic pulmonary fibrosis and other progressive fibrosing interstitial lung diseases?

Jascayd vs Ofev for ILD Treatment

Jascayd (nerandomilast) is not mentioned in current major international guidelines or available evidence, while Ofev (nintedanib) has strong guideline support and FDA approval for both idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases. 1, 2

Current Guideline Recommendations for Nintedanib (Ofev)

The 2022 ATS/ERS/JRS/ALAT guidelines make a conditional recommendation for nintedanib in progressive pulmonary fibrosis (PPF), making it the only antifibrotic with formal guideline endorsement for non-IPF progressive fibrosing ILDs. 1

Established Efficacy of Nintedanib

• In IPF: Nintedanib reduces annual FVC decline by approximately 125 ml compared to placebo (INPULSIS trials), demonstrating clear disease-modifying effects 2, 3

• In progressive fibrosing ILD: Nintedanib reduces annual FVC decline by 107 ml compared to placebo across diverse ILD subtypes 2, 4

• In systemic sclerosis-ILD: Nintedanib reduced annual FVC decline to -52.4 ml/year versus -93.3 ml/year with placebo (p=0.04) 5

• Acute exacerbation reduction: In IPF, nintedanib reduces the risk of acute exacerbations (HR 0.16; 95% CI, 0.04-0.70) 2

Standard Dosing Protocol for Nintedanib

• Start at 150 mg twice daily - this is the evidence-based dose that demonstrated efficacy in all major trials 2, 5

• Reduce to 100 mg twice daily only if intolerable adverse effects occur, particularly persistent gastrointestinal symptoms 2, 6

• Never start at the lower dose - all patients should begin at 150 mg twice daily unless contraindicated 2

Adverse Effect Profile of Nintedanib

Common Gastrointestinal Effects (Compared to Placebo)

• Diarrhea occurs in 62-76% of patients (versus 18-32% with placebo) 2, 5
• Nausea is 3.1-fold more frequent 2
• Vomiting is 3.6-fold more frequent 2
• Abdominal pain is 4.2-fold more frequent 2
• Weight loss is 3.7-fold more frequent 2

Hepatic Monitoring Requirements

• AST/ALT elevations are 3.2-3.6 times more frequent than placebo 2, 6

• Monitor liver enzymes monthly for 3 months, then every 3 months thereafter 2, 5

• Permanent discontinuation required if liver enzyme elevations don't resolve with dose reduction 2

Treatment Discontinuation Rates

• Adverse events lead to permanent dose reduction 7.9 times more frequently than placebo 2, 6

• Treatment discontinuation occurs 1.9 times more frequently with nintedanib 2

• Diarrhea leads to discontinuation in less than 5% of patients when managed appropriately 3

Clinical Application Algorithm

For IPF Patients

1. Confirm IPF diagnosis using 2022 ATS/ERS criteria with HRCT and/or biopsy 1

2. Initiate nintedanib 150 mg twice daily regardless of disease severity 2

3. Monitor monthly for first 3 months: liver enzymes, weight, gastrointestinal symptoms 2, 5

4. If persistent diarrhea develops: reduce to 100 mg twice daily rather than discontinuing 2

5. Continue monitoring every 3-6 months: PFTs, weight, liver enzymes 1, 5

For Progressive Fibrosing ILD (Non-IPF)

PPF must be defined as at least 2 of 3 criteria within the past year: 1

• Worsening respiratory symptoms
• FVC decline >5% predicted OR DLCO decline >10% predicted
• Radiological progression (increased traction bronchiectasis, new ground-glass with traction bronchiectasis, new/increased reticulation, new/increased honeycombing, increased lobar volume loss)

Once PPF is confirmed, initiate nintedanib 150 mg twice daily using the same monitoring protocol as IPF 1, 2

For Systemic Sclerosis-ILD

• Nintedanib 150 mg twice daily is recommended either as monotherapy or in combination with mycophenolate mofetil 5

• The treatment effect is consistent regardless of concurrent mycophenolate use (26.3 ml/year additional FVC preservation with MMF, 55.4 ml/year without) 5

• Strongly avoid daily glucocorticoids due to increased scleroderma renal crisis risk 5

Critical Pitfalls to Avoid

• Do not delay treatment initiation - early treatment preserves more lung function 2

• Do not discontinue prematurely for diarrhea without attempting dose reduction to 100 mg twice daily 2

• Do not add nintedanib to stable patients on mycophenolate without documented progression - this is conditionally recommended against due to cost, adverse effects, and limited efficacy data 6, 5

• Do not use nintedanib in patients with creatinine clearance <30 mL/min without careful dose adjustment 6

Absence of Evidence for Jascayd

No guideline recommendations, FDA approval, or published clinical trial data exist for Jascayd (nerandomilast) in the treatment of IPF or progressive fibrosing ILD. Without established efficacy data, safety profiles, or regulatory approval, Jascayd cannot be recommended as an alternative to nintedanib for any ILD indication at this time.