Background Major progress in the treatment of Rheumatoid Arthritis (RA) has followed the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDS) into clinical practice. However, concern exists over their use in patients with concomitant interstitial lung disease (ILD), due to the reported risk of ILD exacerbation. This poses a significant problem given the prevalence of ILD in up to 10% of RA patients. We have previously reported the case of a patient with RA-ILD in whom treatment with abatacept (ABA) was associated with an improvement in several lung parameters.
Objectives To systematically review the impact of ABA upon ILD.
Methods We searched Medline, Embase and Cochrane databases from their inception until Sept 2014.ACR, BSR and EULAR abstracts from 2012 and 2013 were also screened. We selected all reports in human subjects who had been administered ABA and had evidence of ILD. The quality of the selected studies was stratified according to the Oxford Centre for Evidence Based Medicine Evidence (2001 update). A manual search of the references of included studies was also performed.
Results A total of 152 citations were identified, with 21 selected for review. Four were suitable for quantitative analysis (1 meta-analysis and 3 observational studies), 3 for qualitative analysis (3 case studies).The remaining 13 articles were included as supplementary evidence. In a meta-analysis in which data from 8 RA clinical trials were pooled (3173 ABA treated patients with 2331 patient years of exposure in the short term and 4149 treated patients with 12 132 patient years of exposure in the long term), ILD occurred in 2 patients in the short term period (Incidence Rate (IR) of 0.09, 95% CI 0.01, 0.31) compared with no events in the control group. During the pooled long term period, ILD was reported in 11 patients giving an IR of 0.11 (95% CI 0.06, 0.20) . In summary, ABA had a low IR of ILD in both short term and long-term, with no apparent increase over time. Another study reviewed 2683 new ABA treatment episodes taken from MarketScan (1775 total person years) and MediCare databases (1767 total person years), of which an IR of 1.1 (95% CI, 0.1, 4.1) and 4 (95% CI, 1.6, 8.2) respectively were found. Two observational studies with sample sizes of 25 and 12 respectively also concluded that ABA did not increase the prevalence of ILD events. Of the published case reports and series, all but one showed improvements in ILD-related parameters after ABA. In the outlying case, the exact cause for deterioration of chest CT changes was uncertain. Supplementary evidence suggested that ABA use was not contra-indicated in ILD patients.
Conclusions There is limited data available on the relationship between ABA and ILD. Case reports suggest that ABA may improve pre-existing ILD, however one case exists of potential worsening of interstitial pneumonia. Several studies concluded that there was no increased IR of ILD events in patients receiving ABA treatment. Whether ABA should be used as the biologic of choice in RA-ILD patients requires further research.
Weinblatt, M. E., Moreland, L. W., Westhovens at al. (2013) ‘Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: Integrated analyses of up to 8 years of treatment from the abatacept clinical trial program’, Journal of Rheumatology, 40(6), 787-797.
Disclosure of Interest D. Nelson: None declared, M. McLaughlin: None declared, A. Östör Speakers bureau: Consulting and expert testimony fees for expert opinion, honoraria for lectures; fees for the development of educational presentations and aids; and travel expenses to attend conferences from all or some of the following: Roche, Chugai, MSD, Abbvie, Pfizer, BMS & Lilly.