Rheumatoid arthritis

Serial ACPA measures unnecessary in seronegative RA patients


Repeat testing for autoantibodies that signal more severe disease in rheumatoid arthritis patients that are seronegative for the biomarkers after treat to target therapy is started is neither helpful or cost effective, say Australian rheumatologists.

That’s because patients who are double negative for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) are highly unlikely to ever seroconvert to the ACPA positive serology associated with more aggressive disease and worse prognosis, a prospective study shows.

Rheumatologist Professor Alistair Reid from the Department of Medicine at the University of Wollongong and colleagues from the Department of Rheumatology at the Royal Adelaide Hospital conducted a large prospective study investigating the prevalence of seroconversion to ACPA after commencement of triple DMARD treat-to-target therapy in seronegative patients.

Speaking to the limbic, Professor Reid said the risk of seroconversion in this group of patients is extremely low – less than 1%.

He says the common practice of ordering serial ACPA measures in seronegative RA patients is unnecessary and scrapping repeated testing in this group could save the health system ‘a huge amount’ of money.

Despite 20-25% of RA patients being double seronegative it’s been debatable whether seronegative patients should be retested once treatment starts, Professor Reid explains.

“The hypothesis is that people would convert from seronegative to seropositive and there is a temptation to repeat testing to confirm a RA diagnosis. There is also some sentiment that serial testing could be prognostically and therapeutically helpful – if someone became ACPA positive they would be more likely to develop erosive disease.”

But among 154 patients in the study who were seronegative for ACPA at baseline, the rate of seroconversion after a median five-year follow up was low (6.5%) and persistent seroconversion lower still (2.6%).

Only one of 107 patients who were double seronegative at baseline subsequently seroconverted to ACPA positivity and this was transient.

The findings suggest that the combination of ACPA and RF at diagnosis is highly sensitive for seropositive RA and that there is ‘no utility’ for ongoing testing for ACPA and RF in double seronegative patients, Professor Reid says.

Meanwhile, the rates of RF seroconversion (26.5%) and retroversion (47.4%) during follow up were much higher, while the rate of persistent RF seroconversion to positive was low at 8% – suggesting that RF positivity is less stable and potentially more responsive to disease suppression.

“What we’ve shown is that after you’ve got clinically apparent disease, people don’t convert from seronegative to positive,” Professor Reid says, adding that the seroconversion happens at some time before patients become symptomatic.

“We had that information, to some degree, for seropositive people – that the seroconversion event was likely to happen years to many years before clinically apparent arthritis appeared. But we didn’t know for seronegative disease whether people might go on to later seroconvert.”

What the study now shows is that if seroconversion is going to happen, it happens before clinically relevant disease appears.

“If you have clinically apparent seronegative arthritis you won’t then convert to ACPA and it’s not worth checking for … it’s not a useful prognostic tool because seroconversion just doesn’t happen [in this group]”.

It’s also a significant cost to the public purse for no therapeutic benefit, says Professor Reid, noting that patients could have 10 to 20 or even more ACPA measurements taken over the course of their therapy.

“At $35 a test we’re talking about $700 a patient saved. Multiply that over the 1% of the population that’s estimated to have rheumatoid arthritis and that ends up being a huge amount of money saved to the health budget.”

“What we’re really saying is: patients need one ACPA measurement test if they present to a rheumatologist with active inflammatory rheumatoid arthritis. If they’re ACPA and RF negative at baseline then we don’t need to test those markers again in the future. That can be a huge cost saving to medical expenditure if those tests aren’t done.”

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