Does nintedanib (generic name) cause weight loss?

Does Nintedanib Cause Weight Loss?

Yes, nintedanib significantly causes weight loss as a well-established adverse effect, occurring 3.7 times more frequently than placebo in patients with progressive pulmonary fibrosis. 1

Magnitude and Frequency of Weight Loss

Weight loss is one of the most common gastrointestinal adverse effects of nintedanib therapy:

• Weight loss occurs 3.7 times more frequently in nintedanib-treated patients compared to placebo across all progressive pulmonary fibrosis populations 1, 2, 3
• In real-world clinical practice, mean weight loss during the first 6 months averages 3.2 kg (approximately 5% of body weight) 4
• Weight loss is consistently reported alongside other gastrointestinal effects including diarrhea (2.8 times more frequent), nausea (3.1 times more frequent), vomiting (3.6 times more frequent), and anorexia (2.8 times more frequent) 1, 2, 3

Clinical Significance and Monitoring Requirements

Weight loss during nintedanib therapy has important prognostic implications and requires systematic monitoring:

• Weight loss ≥5% over the first year predicts worse survival regardless of underlying disease type (IPF vs non-IPF) or baseline body mass index 5
• Weight loss of CTCAE grade ≥2 is an independent predictor of all-cause mortality (hazard ratio 2.448,95% CI 1.080-5.551) 4
• Patients with weight loss ≥5% show significantly higher rates of nintedanib discontinuation 5

Monitoring recommendations from major guidelines:

• The American College of Rheumatology/American College of Chest Physicians recommends monitoring for weight loss during nintedanib therapy 1
• Liver function tests should be performed monthly for 3 months, then every 3 months, while simultaneously monitoring for diarrhea and weight loss 1
• The American Thoracic Society recommends monitoring for weight loss during pirfenidone therapy (which also causes weight loss), suggesting this is a class-wide concern for antifibrotics 1

Risk Factors for Weight Loss

Specific patient characteristics predict higher risk of weight loss:

• Low baseline body weight and BMI are the strongest predictors of significant weight loss (≥5%) during nintedanib therapy 5, 4, 6
• Older age is associated with increased risk of weight loss 5
• Poor performance status at treatment initiation increases susceptibility to gastrointestinal adverse effects including weight loss 6
• Full dosage (150 mg twice daily) at treatment initiation versus dose escalation increases risk 6

Management Strategies

When weight loss occurs, consider these evidence-based approaches:

• Temporary dose reduction to 100 mg twice daily or treatment interruption may be necessary for persistent gastrointestinal effects 2, 3
• Adverse events lead to permanent dose reduction 7.9 times more frequently with nintedanib than placebo 1, 2
• Treatment discontinuation occurs 1.9 times more frequently with nintedanib 1, 2
• Addition of prednisolone to the treatment regimen may help prevent gastrointestinal adverse effects, though this is based on limited evidence 6

Important Clinical Caveats

The weight loss associated with nintedanib must be distinguished from disease-related weight loss:

• Weight loss is a known complication and prognostic indicator of IPF itself, independent of treatment 4
• In one study, mean weight change 6 months before nintedanib was compared to 6 months after, showing significant additional weight loss attributable to the drug (mean difference -2.5 kg, 95% CI -3.6 to -1.4) 4
• This confirms that nintedanib causes weight loss beyond any disease-related decline 4

Despite causing weight loss, nintedanib provides important clinical benefits:

• Nintedanib reduces annual FVC decline by approximately 107-125 ml compared to placebo 2, 3, 7
• It decreases the risk of ILD progression 2.4-fold 2, 3
• The drug is conditionally recommended by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association for progressive pulmonary fibrosis 1, 2

Careful body weight monitoring provides useful information for predicting long-term tolerability and mortality risk in patients treated with nintedanib. 5