My last blog discussed the Rheumatoid Factor, its significance, and perhaps its insignificance. The bottom line, however, is that rheumatologists are on a seemingly never-ending quest to find ways to predict who among our patients will have a worse outcome, and therefore are perhaps deserving of being treated aggressively even before their clinical presentation shows aggressive disease.
A study presented by Dr. Hitchon of the University of Manitoba in Canada tried to sort out what a rheumatologist is to do, as she understands that those of us on the front lines of treating rheumatoid arthritis patients need prognostic indicators to guide our treatment decisions, so that the appropriate drug is used without unnecessary cost or potential toxicity to the patient.
Patients’ response to treatment is a function of how their immune systems function, and the function of the immune system is reflected in laboratory markers called cytokines. And so Dr. Hitchon’s study looked at cytokines which cause inflammation and those which fight inflammation in patients being treated for their inflammatory arthritis.
The study looked at patients with inflammatory arthritis who have had arthritis for no more than one year, and who had never been treated with disease modifying drugs (for example, methotrexate, sulfasalazine, leflunomide). These patients were than separated into 3 groups: those with rheumatoid arthritis, those with undifferentiated arthritis, and those with spondyloarthropathies.
Rheumatoid factor was positive in 85% of the rheumatoid arthritis patients, 33% of the undifferentiated arthritis patients, and in 0% of the spondyloarthropathy patients. In addition, the rheumatoid arthritis group was more likely to be CCP antibody positive, which in turn is associated with a lower rate of remission. CCP antibodies were positive in 70% of the rheumatoid arthritis group, 13% of the undifferentiated arthritis group and 6% of the spondyloarthropathy group (and this 6% accounted for all of the psoriatic arthritis patients). There was bone destruction due to inflammation in 15% of the rheumatoid arthritis patients, but not in the other two groups.
Two groups were identified based on cytokine levels upon entry into the study, with one group having more of both the pro- and anti-inflammatory cytokines. The group with the higher amounts of cytokines trended toward more disease activity and the patients were more likely to be rheumatoid factor positive and CCP antibody positive.
After one year the group with the higher amounts of cytokines was more likely to be on methotrexate, and in fact was using multiple drugs for their arthrtitis. Despite the use of stronger medications, this group had a significantly lower rate of remission.
Although the findings did not show that cytokines concentrations were 100% correlated with poor response to treatment, it is a beginning. And more studies are indicated.