Interstitial lung disease following certolizumab pegol

Sir, Interstitial lung disease (ILD) has been reported in the literature following treatment with anti-TNF, but never before with certolizumab pegol. We report a case of a 71-year-old lady with an 8-year history of seropositive (RF and anti-CCP) RA who developed ILD after eight doses of certolizumab in combination with MTX. Before commencing this medication, she had severely active RA [28-joint DAS (DAS-28) 5.9 and 5.69] and had failed to respond to conventional DMARD therapy with MTX 25 mg orally weekly and SSZ 1 g bd. She was otherwise fit and well. She was a life-long non-smoker, at low risk of tuberculosis (TB) on history, with no evidence of TB or ILD on physical examination or chest X-ray. After seven doses of etanercept, she developed recurrent injection-site reactions, and was switched to certolizumab. She received eight doses at 2-weekly intervals, and her RA went into remission with DAS-28 reducing to 1.89. However, she attended a routine rheumatology clinic appointment complaining of a 5-day history of shortness of breath and dry cough. On examination, her temperature was 38.4°C, respiratory rate 34, oxygen saturations 88% on air at rest, heart rate 92 and blood pressure 124/88. Auscultation of the chest revealed widespread fine inspiratory crepitations. Arterial blood gas on air showed partial pressure of oxygen in arterial blood (PAO2) of 7.48. CXR showed patchy consolidation in both lung fields. She commenced oral prednisolone 20 mg and oral clarithromycin and amoxicillin on the advice of the respiratory physicians while awaiting high-resolution CT (HRCT) scan of her chest and bronchoscopy with bronchoalveolar lavage (BAL) to differentiate atypical infection from non-infectious ILD. The HRCT showed extensive ground glass shadowing affecting all lobes of the lungs, which was more extensive in the peripheries (Fig. 1). The widespread distribution and lack of any focal consolidation favoured a non-infectious aetiology. Microbiological analysis of BAL fluid showed no evidence of active infection. A transbronchial biopsy was not performed due to the low likelihood of obtaining a diagnostic sample and the patients reduced respiratory function at the time. HRCT of the lower zones showing extensive ground glass shadowing, more extensive in the peripheries than central areas. She commenced i.v. methylprednisolone 1 g daily for 3 days following these procedures. Extensive microbiological tests were all negative, including two sets of blood cultures, sputum culture and an atypical pneumonia screen for legionella. BAL showed no fungal elements or white cells on microscopy, nor acid-fast bacilli. Cultures were sterile, including a 42-day culture for TB. Lower respiratory pathogens (including pnenumocystis) were not detected by IF. However, a report from the reference laboratory detected Pneumocystis jirovecii by PCR at a level more in keeping with colonization. This was interpreted with the clinical picture and appearances at BAL and it was concluded that this was low-level colonization and not clinically significant. Her condition plateaued as soon as treatment commenced and she remained an inpatient for observation for 2 weeks. She was discharged home with resting saturations on air of 95%, but required home oxygen due to rapid desaturation on exertion. Her discharge medication was prednisolone 20 mg daily, lansoprazole, calcichew D3 forte and alendronic acid; and, in addition, her admission medication of aspirin, detrusitol and simvastatin. MTX and certolizumab were both stopped on admission. She made no significant recovery by her most recent review after 2 months. She continues to have resting oxygen saturations of 92% and bilateral crepitations on examination, with rapid desaturation on exertion still requiring home oxygen. Certolizumab pegol is a Pegylated FAb fragment of a humanized mAb directed against TNF-α [1]. It was licensed in June 2009 by the European Medicines Agency for treatment of RA. In February 2010, it was recommended by the National Institute for Health and Clinical Excellence (NICE) for treatment of people with RA who have already tried MTX and another DMARD, usually for at least 6 months, and have severe active RA, as assessed by a rheumatologist on two separate occasions [2]. A search of the literature found no previous reported cases of ILD following treatment with certolizumab pegol. However, onset or exacerbation of ILD is emerging as a recognized adverse drug reaction to anti-TNF drugs. Two recent articles published by the biologic registry of the Spanish Grupo de Estudio de Enfermedades Autoinmunes (GEAS) (BIOGEAS) Study Group from Spain describe 122 cases of ILD following biologic therapies, overwhelmingly (97%) attributable to anti-TNF, and in the vast majority (89%) used for treating RA [3, 4]. Patients have a poor prognosis, with an overall mortality rate of around one-third, rising to two-thirds in patients with pre-existing interstitial disease. This association is well enough recognized that in fact ILD is described as a rare event (estimated between 1 and 10 in 10 000 users) in the summary of product characteristics (Table 1 in Ref. [1]), even though there have been no reports from the three trials of certolizumab pegol [Rheumatoid Arthritis PreventIon of structural Damage (RAPID1 and RAPID2) or EFficAcy and Safety of cerTolizumab pegol– 4 Weekly dosAge in RheumatoiD arthritis (FAST4WARD)] or their on-going extensions [5–9]. In summary, clinicians should remain vigilant to the development of ILD in RA patients receiving anti-TNF therapy including certolizumab. Disclosure statement: The authors have declared no conflicts of interest.