Thursday, 21 Mar 2019

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Spotlight on Interstitial Lung Disease at ACR 2018

Here are a few important advances in our understanding of interstitial lung disease (ILD) from the ACR 2018 meeting last week.

  • MUC5B promoter variant  and RA-ILD - Recently reported in both the NEJM and as a plenary session at the ACR 2018, Juge et al reported that a gain-of-function MUC5B promoter variant, rs35705950, would also contribute to the risk of rheumatoid arthritis (RA)–associated interstitial lung disease (ILD).  An analysis of 620 patients with RA-ILD and  614 patients with RA without ILD, and 5448 unaffected controls revealed an association between the minor allele of the MUC5B promoter variant rs35705950 in RA-ILD patients (adjusted OR  3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10−17) and was significantly (5 fold higher) overrespresented in RA-ILD patients.  Lastly, the MUC5B promoter variant was associated with an increased risk of ILD among RA patients (aOR 3.1; 1.8 to 5.4).
    • There was no significant association with the MUC5B promoter variant and the diagnosis of RA alone and this promoter variant is not associated with ILD among patients with systemic sclerosis.
    • Thus, the MUC5B promoter variant rs35705950 is a risk factor for RA-ILD (UIP pattern).  While being clearly important from understanding the pathogenesis of RA-ILD, it is unclear when MUC5B genotyping would prove useful in assessing prognosis or guiding management of either disease.
  • ILD and Disease Activity - Dr. Jeff Sparks oral presentation on ILD took a prospective analysis of the BRASS cohort (1,281 RA patients) with a median RA duration was 9 years and found 86 cases of incident ILD.  They showed that moderate to high disease activity had significantly increased the risk of ILD  (HR 2.41; 95%CI 1.37-4.25). Seropositivity was also strongly associated with ILD risk (HR 2.69, 95%CI 1.38-5.27). 
  • Seropositivity and Lung Disease - Huang and colleagues also looked at 1500+ RA patients from the BRASS registry who had CT scans of the chest and found that Seronegative patients were just as likely as seropositive patients to have lung abnormalities like lung nodules (RF- 36% vs RF+ 40%), ILD (16% vs 15.9%), pleural effusions (10% vs 9.4%), etc.  Suggesting that RA lung findings are not just limited to the seropositive RA population. 
  • ACPA+ and ILD -  Alemao et al examined claims data on over 177,000 with ACPA testing, finding ACPA+ in 11% of this cohort.  While ACPA positivity, in the general population, was more frequently associated with an ILD diagnosis (Incidence rate 13.3 vs 8.4 per 1000PY; compared to ACPA negative) the rate of ILD among RA patients was not influenced by ACPA positivity (IR 12.9 vs 11.7 per 1000 PY). 


The author has no conflicts of interest to disclose related to this subject

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