Family History Linked to Rheumatoid Arthritis, but Can It Also Be Linked to Treatment Effectiveness?

Clinical research has firmly established that family history of rheumatoid arthritis (RA) is among the strongest risk factors for developing RA. Less study has been undertaken regarding hereditary factors as a predictor of response to treatment. A recent Swedish study in Annals of the Rheumatic Diseases took aim at that prime target. It also sought to identify a link between heredity and the clinical presentation of RA, which is dependent on a number of factors beyond direct genetic links.

Sweden is a rich clinical environment for looking at long-term hereditary links, in part because of a national, somewhat centralized system put in place in the 1950s and more or less continuing today. While the country’s system is not without faults—notably, coordination of care among hospitals, primary care physicians, and county health care facilities—it is widely regarded as one of the best in the world. Although coordination of care is an issue, there are several well-established registries that allow for comprehensive studies of treatment outcomes over multiple generations.

The Annals study looked through years of data collected through the Swedish Multi-Generation and Patient registers for family history of RA. Clinical presentation was examined among patients with early RA 2000—2011 (symptom onset <12 months before inclusion, N=6869), and response to methotrexate (MTX) monotherapy in the subset starting this treatment (N=4630). Family history of RA was defined as diagnosed RA in any first–degree relative.

The study authors looked at the clinical response in patients who were given tumor necrosis factor inhibitors (TNFi) as the first biological disease-modifying anti-rheumatic drug. Effectiveness of the drug was estimated using linear and generalized logistic regression models. The results were examined in correlation to family history with clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months. The results were then measured against relatives’ response to the same (or very similar) treatment.

The study revealed that patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. According to the study authors, “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).”

Interestingly, however, having a relative who discontinued TNFi treatment within a year increased the odds of doing the same, despite that lack of familial correlations in change in disease activity measures. Future research will likely focus on hereditary similarities to other RA treatments.