Background/Purpose:

Exacerbation of interstitial lung disease (ILD) is a problem when biologics are administrated in patients with RA, and not a few fatal cases have been reported in Japan.  According to the post-marketing surveillance report of TNF blockers, the development/exacerbation rate of ILD was 0.5 %.  In our department, however, the rate was 5 % probably because we have many RA cases with ILD.  We have shown that in patients with pre-existing ILD, the rate is nearly 30%.  In japan there are 6 biologics available for the treatment of RA, 4 of which are TNF blockers and 2 are non-TNF blockers.  Here we compared the incidence of exacerbation of pre-existing ILD in patients administrated with TNF blockers and non-TNF blockers.

Methods:

Subjects were 58 patients with RA, with the mean age of 66.  As a part of workup before administration of biologics, chest CT scan was done.  After administration of biologics, chest X-ray film (CXR) was taken at least every 3 months.  When newly developed shadows were found on CXR or when patients complained of respiratory symptoms for more than 2 weeks, chest CT scan was done again.  The severity of ILD was graded into 3, grades 1 to grade 3, according to the extent of ILD on chest CT.  The biologics administrated were infliximab (IFX) for 8, etanercept (ETN) for 36, adalimumab (ADA) for 2, tocilizumab (TCZ) for 9 and abatacept (ABT), respectively.  The duration of observation was 12 months, except when the biologics were withdrawn because of exacerbation of ILD. 

Results:

The ILD of 30, 22 and 6 patients were graded into grade 1, 2 and 3, respectively.  The ILD exacerbated in 14 subjects (24.1 %); the duration from the introduction of biologics to the exacerbation was from 1 to 12 months with the median of 7 months.  The biologics used at the exacerbation of ILD were IFX in 5, ETN in 8, ADA in 1, TCZ in 0 and ABT in 0, respectively.  The incidence of ILD exacerbation with TNF blockers and non-TNF blockers were 30.4 % (14/46) and 0 % (0/12), respectively, and there was a significant difference between them (p = 0.024).There were no differences between the subjects with ILD exacerbation and those without it in age, gender, RF titer, the ILD grade, KL-6 concentration, and the dose of prednisolone and MTX.  The KL-6 concentration increased significantly when ILD exacerbated (p < 0.05).  The biologics were withdrawn in 11 of 14 subjects with ILD exacerbation, and 2 subjects with ILD grade 2 and 3 died due to respiratory failure.

Conclusion: The exacerbation rate was high in patients with pre-existing ILD when TNF blockers were administrated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-incidence-of-exacerbation-of-pre-existing-interstitial-lung-disease-ild-is-higher-in-tnf-blockers-than-in-non-tnf-blockers-in-ra/