Esbriet (Pirfenidone) vs Other IPF Drugs: Full Comparison and Guidance

Esbriet is a pirfenidone‑based antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF), launched in the UK in 2013 after European approval in 2011. Patients with IPF often wonder whether Esbriet is the best option or if newer drugs might suit them better. This guide breaks down the science, real‑world outcomes, and practical considerations so you can decide with confidence.

TL;DR - Quick Takeaways

• Esbriet (pirfenidone) and Nintedanib are the two FDA‑approved antifibrotics for IPF.
• Pirfenidone works by dampening inflammation and collagen‑building pathways; Nintedanib blocks multiple growth‑factor receptors.
• Both drugs slow decline in forced vital capacity (FVC) by ~45‑50% in trials, but side‑effect profiles differ.
• Cost in the UK ranges from £2,700‑£3,200 per year for pirfenidone and £3,400‑£4,000 for nintedanib.
• Emerging therapies (Pamrevlumab, PRM‑151) show promise but remain investigational.

What is Idiopathic Pulmonary Fibrosis?

Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterized by scar tissue replacing normal lung architecture, leading to breathlessness and reduced oxygen exchange. The cause is unknown, hence “idiopathic”. Without treatment, average survival after diagnosis is 3‑5 years.

How Pirfenidone (Esbriet) Works

Pirfenidone is a small‑molecule that interferes with several fibrogenic pathways:

1. Inhibits transforming growth factor‑beta (TGF‑β) signalling, a key driver of fibroblast activation.
2. Reduces production of inflammatory cytokines such as interleukin‑1β and tumor necrosis factor‑α.
3. Acts as an antioxidant, limiting oxidative stress that fuels tissue damage.

These actions translate into a measurable slowdown of lung function loss, as shown in the CAPACITY trial (Phase III, 2011) and the ASCEND trial (Phase III, 2014). Both studies reported a 48‑50% reduction in the rate of FVC decline compared with placebo.

Alternative Antifibrotics - The Main Contenders

The only other drug with full regulatory approval for IPF is Nintedanib (brand name Ofev). It belongs to the tyrosine‑kinase inhibitor (TKI) class and blocks receptors for platelet‑derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). By hitting three pathways at once, nintedanib also cuts the annual FVC decline by roughly 45%.

Beyond these two, several agents are in late‑stage development:

• Pamrevlumab is a monoclonal antibody against connective tissue growth factor (CTGF), showing a 30% reduction in FVC loss in a Phase II trial.
• PRM‑151 is recombinant human pentraxin‑2 that modulates macrophage activity; early data suggest improved six‑minute walk distance.
• Other pipeline drugs include LPA antagonists (e.g., BMS‑986020) and JNK inhibitors, but they remain experimental.

Side‑Effect Profiles - What to Expect

Both approved drugs have predictable adverse‑event patterns that influence choice.

Choosing the Right Therapy - Decision Factors

When you sit down with a respiratory specialist, they’ll weigh several variables:

• Comorbidities: Patients with active liver disease may favour nintedanib, while those with chronic diarrhoea might prefer pirfenidone.
• Medication Adherence: Pirfenidone requires three daily doses, which can be challenging for people with complex regimens.
• Drug Interactions: Both drugs are metabolised by CYP1A2 (pirfenidone) and CYP3A4 (nintedanib). Strong inhibitors or inducers must be reviewed.
• Insurance / NHS Funding: In the UK, both are listed on the NHS prescribing database, but local formularies can sway the first‑line choice.
• Patient Preference: Some patients accept mild rash in exchange for fewer GI events, while others value once‑daily dosing.

In practice, about 55% of UK IPF patients start on pirfenidone, with the remainder on nintedanib, according to the British Thoracic Society audit 2022.

Managing Side‑Effects - Practical Tips

For Pirfenidone

• Food Timing: Take each dose with a substantial meal; this reduces nausea and improves absorption.
• Sun Protection: Because of photosensitivity, wear sunscreen (SPF30+) and avoid prolonged sun exposure.
• Liver Monitoring: Baseline liver function tests (LFTs) then every 3months; pause the drug if ALT/AST >3× ULN.
• Rash Management: Use moisturisers, antihistamines, or low‑dose steroids if needed.

For Nintedanib

• Diarrhoea Control: Start with a lower dose (100mg×2) for the first two weeks, then titrate up. Loperamide 2mg after each loose stool can be effective.
• Hydration: Keep fluid intake above 2L/day to mitigate GI irritation.
• Liver Surveillance: Same schedule as pirfenidone; dose‑reduce if enzymes rise.
• Cardiovascular Review: In patients with a history of myocardial infarction, discuss risk vs benefit.

Emerging Therapies - What’s on the Horizon?

Clinical trials for Pamrevlumab (Phase III) and PRM‑151 (Phase II/III) suggest they could complement or replace current antifibrotics. Their mechanisms target upstream signalling rather than downstream collagen synthesis, which may translate into better preservation of lung architecture. However, cost, injection routes, and long‑term safety remain unanswered questions.

Bottom Line - How to Decide

Both Esbriet (pirfenidone) and Nintedanib provide a meaningful slowdown of disease progression, but the “best” choice hinges on individual health status, tolerance for side‑effects, and lifestyle preferences. If you value a three‑times‑daily dose and can manage mild GI upset, pirfenidone’s anti‑inflammatory profile may feel safer. If once‑daily dosing and a stronger anti‑angiogenic effect matter more, nintedanib could be the better fit. Always discuss liver test results and medication interactions with your specialist before starting or switching.

Frequently Asked Questions

Can I take both pirfenidone and nintedanib together?

Current evidence does not support combined use; overlapping toxicities, especially liver enzyme elevations, increase the risk. Trials are exploring sequential or combination strategies, but standard practice is to choose one agent.

How long do I need to stay on Esbriet?

IPF is chronic; stopping treatment usually leads to a rebound in disease progression. Patients typically remain on pirfenidone for the rest of their lives unless intolerable side‑effects develop.

Does pirfenidone interact with common over‑the‑counter meds?

Yes. Strong CYP1A2 inhibitors (e.g., fluvoxamine) can raise pirfenidone levels, increasing toxicity. Antacids taken within 30minutes of the dose may reduce absorption. Always check with a pharmacist.

What monitoring is required after starting therapy?

Baseline pulmonary function tests (FVC, DLCO), liver function, and a full blood count. Follow‑up at 3months, then every 6months, adjusting dose based on tolerability and laboratory results.

Are there any diet restrictions with pirfenidone?

No strict restrictions, but a high‑fat meal can increase drug absorption and potentially worsen GI side‑effects. A balanced diet with regular meals is recommended.

How does the cost of Esbriet compare to nintedanib in the UK?

Pirfenidone typically costs £2,800‑£3,200 per year, while nintedanib averages £3,400‑£4,000. NHS prescribing policies may subsidise both, but local formularies sometimes favour the cheaper option.

What are the most common reasons patients stop pirfenidone?

Intolerable gastrointestinal upset, photosensitivity rash, and significant liver enzyme elevation are the leading causes for discontinuation.