Patients with rheumatoid arthritis who carry a specific allele of the gene MUC5B have about double the risk of developing interstitial lung disease when compared with noncarriers, according to a large Finnish biobank study presented at the annual European Congress of Rheumatology.
Dr. Antti Palomäki
“The risk difference [or carriers relative to noncarriers] started at about age 65, with a bigger difference [for] men than women,” reported Antti Palomäki, MD, PhD, of the center for rheumatology and clinical immunology at Turku (Finland) University.
The gain-of-function MUC5B variant, which encodes mucin 5B, was first linked to RA-associated interstitial lung disease (ILD) more than 3 years ago. At that time, it was already a known genetic risk factor for idiopathic pulmonary fibrosis in the general population. The new data confirm the association in a longitudinal analysis of a large biobank and suggest the association might have clinical utility.
“This is not ready for clinical practice at the moment. We do not yet know whether we can change therapy to reduce risk,” Dr. Palomäki said, adding “in the future we can look.”
One question that might be asked in clinical studies using MUC5B as a tool to assess and modify risk of ILD in patients with RA is whether one therapy is better than another in avoiding or delaying development of lung fibrosis. Dr. Palomäki noted that biologics, for example, might be a more favorable choice in patients with RA who are at high risk of developing ILD.
The association of the MUC5B variant with increased ILD incidence in patients with RA was drawn from a data set known as FinnGen, a biobank collection of epidemiologic cohorts and hospital samples with genotypes of about 10% of the Finnish population. Follow-up extends to 46 years in some of these individuals.
When 248,4000 individuals in this data set were evaluated, 5,534 had a diagnosis of RA. Of these, 178 (3.2%) developed ILD. About 20% of both those with and without RA were MUC5B variant carriers, meaning the remainder were not.
Sex and age factor into lifetime risk
In patients with RA, the lifetime rate of ILD among MUC5B variant carriers was 16.8% versus only 6.1% among noncarriers. This finding translated into a hazard ratio for ILD of 2.27 (95% confidence interval, 1.75–2.96) for variant carriers versus noncarriers.
The lifetime rate of ILD in patients with RA was greater in men versus women regardless of carrier status (18.5% vs. 8.5%). For women, the lifetime rate was lower for carriers, although the difference relative to female noncarriers was greater (14.5% vs. 4.7%).
ILD, whether in the general population or in patients with RA, is a disease of advancing age. When Dr. Palomäki showed a graph, the rise in ILD incidence did not start in any population, whether those with or without RA and regardless of carrier status, until about age 55. In those without RA and in noncarriers of the variant, ILD incidence remained low and began a discernible climb at around age 70.
In those who did not have RA but were positive for the variant, the rates rose more than twice as fast, particularly after age 70. In people who had RA but not the variant, the rate of ILD was greater than in patients who carried the variant without RA, starting the climb earlier and rising more steeply with age. In those with RA and the variant, the climb in ILD incidence rose rapidly after age 65 years even though the incidence remained fairly similar between all of these groups at age 60.