NEW YORK (Reuters Health)—Having a family history of rheumatoid arthritis (RA) does not appear to influence the clinical presentation or treatment response of RA to standard medications, researchers from Sweden report.
“At first we were a bit surprised by our findings,” Dr. Thomas Frisell from Karolinska Institutet in Stockholm told Reuters Health by email. “Patients with a family history of disease should on average have more of the genetic (and some non-genetic) risk factors for developing RA, and I would have guessed that this would be connected to a more severe or active disease, possibly more difficult to treat. In hindsight, the difference in genetic risk factors may not be very large, since all patients with RA are of course at increased levels of these risk factors, or they would not have developed the disease!”
Having a family history of RA increases the risk of RA threefold to fivefold, but whether such a family history influences the prognosis and treatment response once RA develops remains unclear.
Dr. Frisell’s team used data from the Swedish Rheumatology Quality of care register to assess if family history of RA is associated with a different clinical presentation of RA or if it predicts response to methotrexate or TNF inhibitor therapy.
Among more than 6,800 newly diagnosed patients, the 580 (8%) with at least one first-degree relative with RA were slightly more likely to have morning stiffness and slightly less likely to have arthritis in the hand or to have rheumatoid factor, compared with patients without a family history of RA.
There were no significant associations between family history of RA and any measure of response to methotrexate treatment, the researchers report in Annals of the Rheumatic Diseases, online June 19.
Similarly, family history of RA did not predict response to TNF inhibitor treatment three months after the start of such treatment. Slightly more patients with a family history of RA (13%) than without (11%) had switched treatment; among those remaining on treatment, family history of RA was associated with failure to achieve EULAR response. Disease activity changes, however, did not differ between patients with and without a family history of RA.
“Although weak associations can never be ruled out, we were able to reject a strong predictive value in overall family history of RA on the short-term response to either mono-methotrexate or TNF inhibitor therapy,” the researchers note. “We did find lower drug retention rate and EULAR response after 6 months on TNF inhibitors among those with family history of RA, but these associations were too weak to be useful in clinical decisions.”
“Family history of RA is not itself enough to change a clinical decision,” Dr. Frisell said. “We do not yet have evidence enough to be sure if a patient’s family history of response to specific treatments is predictive of treatment response, but our data was in line with this, and it may be expected from several genetic studies.”
Dr. Frisell’s message to patients: “The fact that you have ‘familial’ RA does not mean that you will have a more aggressive disease, or that it will be more difficult to treat.”
Dr. Jeffrey A. Sparks from Brigham and Women’s Hospital’s division of rheumatology, immunology, and allergy in Boston told Reuters Health by email, “There have been studies that show that familial RA occurs earlier and is more often seropositive, which typically has a more severe disease course. Given the size of this study, I was somewhat surprised that those with family history had fairly similar courses compared to those without family history.”
“However, there might be other differences that family history does not adequately measure or might even improve,” Dr. Sparks said. “For example, those with family history are already familiar with the signs and symptoms of RA so might present earlier when treatment is more effective. However, based on self-reported symptoms prior to RA diagnosis, this did not seem to explain the findings of this study.”
“Another previous study found that a particular gene controlling immune function was associated with worse outcomes in RA patients,” Dr. Sparks said. “While family history by itself did not correlate with worse outcomes in RA in this study, there may be particular genes or lifestyle factors that might be important in determining the disease course for RA.”
