Family History and Rheumatoid Arthritis Save

Researchers at the Karolinska Institute have studied their prospective Swedish Rheumatology register to examine the role of a family history of rheumatoid arthritis (RA) on clinical presentation or treatment responses.  Family history is defined as RA in a first-degree relative.

Patients with early RA (N=6869) with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation.

Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7).

Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although they found no significant familial correlations in change in disease activity measures. 

Thus, while a family history of RA may portend a risk for incident RA, in this study it did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi.

These same authors have also published a review of family clustering, recognizing that it may result from genetic and environmental factors shared within families. Nonetheless, assessments of RA in relative risk in first degree relatives has been marred by numerous methodologic issues. (Citation source http://buff.ly/29gc4r6)

Overall they concluded that the risk of RA in FDRs of affected individuals is increased roughly threefold, and in second-degree relatives approximately twofold, with the association being modified by age at onset but not by sex. Twin studies have revealed concordance rates of 12-15% for monozygotic and <4% for dizygotic twin pairs.

Historically, numerous studies published in the 1950s and 1960s reported a stronger familial aggregation for seropositive than seronegative RA.  But more recently a twin study by Silman and colleagues found equal heritability (~67%) in ACPA-positive and ACPA-negative RA patients.