Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Non-Infectious Pulmonary Complications of Biologic Agents for Rheumatic DiseasesA Systematic Literature Review.

Hadjinicolaou2,  Andreas, Bhagat1,  Shweta, Ostor1,  Andrew

Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, Cambridge, United Kingdom
University of Cambridge, United Kingdom

Background:

Systemic inflammatory diseases, such as rheumatoid arthritis (RA) as well as their treatment with disease modifying anti-rheumatic drugs (DMARDS) and anti-TNFa agents may be complicated by a variety of pulmonary disorders. Due to the influx of new biologic agents, we undertook this systematic literature review (SLR) to identify if any of these were associated with non-infectious lung disease.

Methods:

A SLR was conducted in PubMed, the Cochrane Library and EMBASE for reviews, meta-analyses, randomized controlled trials(RCT), clinical trials, case series and reports published up to and including May 2010 using the terms "rituximab""anakinra""certolizumab""golimumab""tocilizumab""abatacept" and "efalizumab" in the advanced search option. Search results were assessed by two independent reviewers. Meeting abstracts from the European League Against Rheumatism and the British Society of Rheumatology annual meetings were included. We manually reviewed references of all the selected publications to complement our search with published data not identified in the initial search or with unpublished data from the Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and manufacturers. Identified articles were included if they reported a possible relationship of biologic agents with lung toxicity, excluded other potential causes or failed to exclude drug-induced causality. A total of 9 RCTs, 15 clinical studies, 10 case series, 35 case reports were identified.

Results:

This SLR revealed possible relationships between some biologic agents and interstitial lung disease (ILD) and other drug-related pulmonary toxicities. No cases of pulmonary toxicity were found with golimumab, certolizumab and efalizumab.

Rituximab(RTX) appeared to have a higher reported rate of ILD as we identified 65 papers reporting at least one case of pulmonary toxicity (148 cases in total). However, RTX was given for a rheumatic disease only in 7 of these studies. In 3 studies in RA and lupus, out of a total of 403 patients involved, there were 3 cases of lung toxicity (1 of ILD and 2 of interstitial pneumonitis, 1 of which was fatal). 4 case reports of RTX (3 given for RA and 1 for lupus) reported 2 cases of Bronchiolitis Obliterans Organising Pneumonia and 2 of ILD with1 death.

3 RCTs of Tocilizumab enrolling a total of 589 patients reported 6 pulmonary adverse events (2 - ILD, 1 - allergic pneumonitis, 3 - interstitial pneumonia). There was 1 case report of fatal exacerbation of RA induced ILD with tocilizumab.

2 RCTs with a total of 1596 patients on Anakinra for RA refractory to DMARDS reported 3 cases of ILD with 2 fatalities.

In all the non-fatal cases, lung pathology was reversible with drug discontinuation and administration of high dose steroid treatment.

Conclusion:

Although the number of reports of pulmonary complications with the newer biologic agents is small, the associated morbidity and mortality is substantial. Drug discontinuation is essential and treatment should be instituted expediously in order to optimise outcomes. Clinicians should remain vigilant for non-infectious pulmonary disease in any patient treated with biologic agents.

To cite this abstract, please use the following information:
Hadjinicolaou, Andreas, Bhagat, Shweta, Ostor, Andrew; Non-Infectious Pulmonary Complications of Biologic Agents for Rheumatic DiseasesA Systematic Literature Review. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :395
DOI: 10.1002/art.28164

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