Background/Purpose: Since family history of RA is among the strongest risk factors for developing the disease, individuals suspected to have RA are routinely asked about their relatives’ disease history. Being a summary measure of a range of genetic and non-genetic risk factors, it would seem likely that family history of RA carries information not only on risk of onset of RA, but also on prognosis, and/or that it may be more strongly associated to certain clinical features of this heterogenic criteria based syndrome. Despite the potential clinical value, and great interest from patients, the role of family history of RA as a clinical marker has been little studied, probably due to the difficulty in ascertaining valid information on familial RA and clinical outcomes.

Methods: We performed a cohort study using prospectively recorded data from Swedish nationwide registers. The cohort was defined as all early RA patients (symptom onset <12 months before inclusion) with a diagnosis of seropositive or seronegative RA in the Swedish Rheumatology register, who started methotrexate monotherapy as first DMARD treatment 2000-2011, and who had parents registered in the Swedish multi-generation register. First degree relatives of cohort members were identified through the Swedish Multi-Generation Register, and the presence of RA among relatives was assessed through the National Patient Register.

The association of RA in one or more first degree relatives to baseline clinical characteristics and treatment response (according to the DAS28-based EULAR response criteria), treatment switch, and change in disease activity measures at 3 and 6 months was estimated using linear regression and generalized logistic regression models.

Results: In our cohort, 380 (9%) of 4210 patients had a first degree relative with RA by their time of RA diagnosis. RA patients with compared to without a family history of RA were more often seropositive (75%/69%), but there were no other significant differences in baseline clinical characteristics (e.g., mean HAQ 0.95/1.01, mean DAS28 5.04/5.06, mean disease duration 0.48/0.49 years). Neither were there any significant differences in treatment response or disease progression at 3 or 6 months, a lack of association that remained after adjustment for sex, age, birth year, and disease duration, and also when further adjusting for baseline DAS28, HAQ, and CRP (Table).

Conclusion: Using a large population-based cohort, we found that despite being a strong predictor of RA itself, family history of RA is not associated with a more severe presentation of RA, nor with short term response to methotrexate monotherapy. Future studies could consider whether family history may be a predictor of long term prognosis or response to treatment other than methotrexate, and what this negative finding implies for the possibility of RA risk genes to also influence disease severity and treatment response.