Can certolizumab (Cimzia) cause organizing pneumonia or nonspecific interstitial pneumonia (NSIP)?

Can Certolizumab Cause Organizing Pneumonia or NSIP?

While certolizumab is not specifically documented in the available evidence as causing organizing pneumonia or NSIP, anti-TNF agents as a class have been associated with paradoxical pulmonary inflammation including granulomatous reactions, and drug-induced interstitial lung disease can manifest as organizing pneumonia or NSIP patterns. 1, 2

Evidence for Anti-TNF Agent Pulmonary Toxicity

The European consensus on inflammatory bowel disease extra-intestinal manifestations specifically notes that granulomatous inflammation compatible with sarcoidosis has been documented in patients receiving anti-TNF monoclonal antibodies, which improves with cessation of the anti-TNF agent and/or steroid treatment 1. This establishes that anti-TNF biologics, the class to which certolizumab belongs, can cause pulmonary inflammatory reactions.

Drug-Induced Interstitial Lung Disease Patterns

Pulmonary drug reactions commonly mimic various forms of idiopathic interstitial pneumonia, including nonspecific interstitial pneumonia (NSIP), organizing pneumonia, diffuse alveolar damage, or usual interstitial pneumonia 2. This means that when certolizumab or other biologics cause lung toxicity, these are the expected radiographic and histologic patterns.

Organizing Pneumonia Characteristics

• Presents with subacute illness with cough and dyspnea (typically <3 months duration) 1
• HRCT shows patchy, often migratory consolidation in subpleural, peribronchial, or bandlike pattern 1
• Characterized histologically by intraluminal plugs of connective tissue in bronchioles extending into alveolar ducts and alveoli 1

NSIP Characteristics

• Presents with dyspnea and cough for months to years 3, 4
• HRCT shows bilateral symmetric ground-glass opacities, predominantly lower lobe subpleural reticular changes, and traction bronchiectasis 3, 4
• Histologically shows alveolar and interstitial mononuclear cell inflammation and fibrosis in a temporally uniform pattern 3

Clinical Approach When Suspecting Drug-Induced Pneumonitis

The identification of pulmonary drug reaction requires stringent interdisciplinary correlation between clinical presentation, radiographic findings, and temporal relationship to drug exposure 2. Key diagnostic steps include:

• Temporal correlation: Document timing of certolizumab initiation relative to symptom onset 2
• Exclusion of infection: Bronchoscopy with bronchoalveolar lavage to rule out infectious causes 1
• Radiographic pattern recognition: HRCT to identify organizing pneumonia versus NSIP patterns 1
• Multidisciplinary discussion: Include pulmonologist, radiologist, and pathologist for consensus diagnosis 3, 4

Management Algorithm

If drug-induced pneumonitis from certolizumab is suspected, the primary intervention is immediate discontinuation of the drug 1, 2:

1. Stop certolizumab immediately upon suspicion of drug-induced lung disease 1
2. Initiate corticosteroids: Most respiratory changes associated with biologics respond to corticosteroids, with route depending on severity 1
3. Monitor response: Clinical improvement after drug cessation supports the diagnosis 2
4. Do not rechallenge: Unlike some targeted therapies where rechallenge may be considered, anti-TNF-induced pulmonary inflammation typically requires permanent discontinuation 1

Important Caveats

• Diagnosis is often by exclusion: A stringent correlation between dose/time of administration and type of reaction exists for only a few drugs, making drug-induced pneumonitis frequently a diagnosis of exclusion 2
• Lung biopsy may be necessary: In cases where clinical and radiographic findings are ambiguous, surgical lung biopsy may be required for definitive diagnosis 2
• Consider underlying disease: Patients with inflammatory bowel disease (the primary indication for certolizumab) have increased baseline risk of pulmonary manifestations independent of drug therapy 1