What are the considerations for using Nintedanib (Nintedanib) in a patient with Chronic Kidney Disease (CKD) and Interstitial Lung Disease (ILD) with a Usual Interstitial Pneumonia (UIP) pattern?

Nintedanib Use in CKD Patients with ILD-UIP

Nintedanib can be used in patients with mild to moderate CKD (creatinine clearance >30 mL/min) at the standard dose of 150 mg twice daily, but should be started at a reduced dose of 100 mg twice daily with careful monitoring in severe CKD (creatinine clearance <30 mL/min), as it has not been formally studied in this population. 1

Renal Dosing and Safety Considerations

Standard Dosing Approach

• For mild to moderate CKD (CrCl >30 mL/min): Start nintedanib at 150 mg twice daily with standard monitoring 1
• For severe CKD (CrCl <30 mL/min): Consider starting at reduced dose of 100 mg twice daily due to lack of safety data in this population 1
• The pharmacokinetics and safety of nintedanib have not been formally studied in patients with severe renal impairment 2

Real-World Evidence in Advanced CKD

• A case report demonstrated successful use of nintedanib in a patient who progressed to stage 3/4 CKD and eventually required hemodialysis, showing good tolerability with only sporadic diarrhea and stable pulmonary function 2
• In this case, renal biopsy showed no correlation between nintedanib use and kidney disease progression 2
• The patient maintained nintedanib therapy even after initiating hemodialysis without toxic effects 2

Efficacy in ILD with UIP Pattern

Disease-Specific Recommendations

• For progressive fibrosing ILD with UIP pattern: Nintedanib reduces the annual rate of FVC decline by approximately 107 mL compared to placebo 1
• Some expert panelists consider nintedanib for patients with a UIP pattern of ILD irrespective of the underlying systemic autoimmune rheumatic disease 3
• In patients with UIP-like fibrotic pattern on HRCT, nintedanib reduced the risk of ILD progression (absolute FVC decline ≥10% predicted or death) with HR 0.69 (95% CI 0.53-0.91; p=0.009) 4

Underlying Disease Considerations

• Systemic sclerosis-ILD: Conditionally recommended as first-line option, though immunosuppressive medications are preferred 3
• RA-ILD with fibrotic/UIP pattern: Some panelists consider nintedanib as first-line therapy, though no consensus was reached 3
• Other autoimmune ILDs: Generally conditionally recommended against as first-line, except when UIP pattern is present 3

Monitoring Requirements

Essential Laboratory Surveillance

• Liver function tests: Monitor monthly for the first 3 months, then every 3 months thereafter 5
• Renal function: Regular monitoring is critical in CKD patients, though specific intervals are not defined in severe CKD 1, 2
• Weight and gastrointestinal symptoms: Monitor for diarrhea and weight loss at each visit 1, 6

Adverse Effect Management

Gastrointestinal Effects (Most Common)

• Diarrhea occurs 2.8 times more frequently than placebo 1
• Abdominal pain occurs 4.2 times more frequently 1
• Nausea occurs 3.1 times more frequently 1
• Management strategy: For persistent diarrhea, reduce dose to 100 mg twice daily or temporarily interrupt treatment 1, 6

Hepatotoxicity

• AST elevation occurs 3.2 times more frequently 1
• ALT elevation occurs 3.6 times more frequently 1
• Adverse events lead to permanent dose reduction 7.9 times more frequently than placebo 1

Treatment Discontinuation

• Overall adverse events lead to treatment discontinuation 1.9 times more frequently with nintedanib 1
• In real-world UK experience, discontinuation rates were manageable across diverse ILD populations 7

Clinical Decision Algorithm

1. Confirm progressive fibrosing ILD with UIP pattern on HRCT and document progression (FVC decline ≥10% predicted within 24 months, or FVC decline 5-10% plus worsening symptoms/imaging) 1

2. Assess renal function:

   • CrCl >30 mL/min: Start 150 mg twice daily 1
   • CrCl <30 mL/min: Consider 100 mg twice daily with enhanced monitoring 1

3. Baseline monitoring: Obtain liver function tests, weight, and assess for gastrointestinal symptoms 5

4. Initiate treatment with proactive counseling about diarrhea management 6

5. Follow-up schedule:

   • Monthly LFTs for 3 months, then every 3 months 5
   • Regular renal function monitoring 2
   • Assess for GI symptoms and weight loss at each visit 1

6. Dose adjustment strategy:

   • If persistent diarrhea or significant GI symptoms: Reduce to 100 mg twice daily 6
   • If LFT elevations: Consider temporary interruption and dose reduction 1
   • If severe adverse effects: Discontinue and consider alternative therapies 1

Important Caveats

• Nintedanib slows disease progression but does not reverse existing fibrosis 1, 5
• The quality of evidence for nintedanib in progressive fibrosing ILD is rated as low to moderate 1
• Combination therapy: Generally recommended against adding nintedanib to mycophenolate in patients without evidence of progression due to cost, adverse effects, and limited efficacy data 3
• In Asian populations, nintedanib showed similar efficacy with manageable adverse events 8
• The INBUILD trial demonstrated consistent benefit across diverse ILD diagnoses including hypersensitivity pneumonitis, autoimmune ILDs, and idiopathic NSIP 9