Creating a Molecular Crystal Ball for PsA

What do we know right now to help identify the 40% to 50% of patients with psoriatic arthritis (PsA) whose disease will progress to painful and disabling joint erosion, deformity, and destruction? Those with high c-reactive protein (CRP) levels and polyarticular disease involving 5 or more joints tend to progress faster, according to the latest research, says Oliver Fitzgerald MD. But that's about all we know.

The new PsA BioDam study, spearheaded by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), intends to improve that situation by identifying a panel of soluble biomarkers that can predict joint damage in psoriatic arthritis in time to slow or even forestall it. 

“It can be quick and fairly cheap," says Fitzgerald, a key BioDam researcher. "But first we need to identify the protein panel.”

At present, while damage can appear as early as within a year after diagnosis, it’s difficult to predict in which patients erosion will develop, and how quickly.

The task ahead is "not only to identify markers, but also to validate them in patients, then find pharmaceutical partners to help develop an assay or assays,” says Fitzgerald, who is Newman Clinical Research Professor at the University College Dublin's Conway Institute for Biomolecular Research.

Candidate markers include cartilage breakdown products, inflammatory markers, and bone biomarkers, FitzGerald told Rheumatology Network in an interview during the 2014 GRAPPA annual meeting in New York.

Among them are CRP and serum amyloid A (SAA), both indicators of inflammation. Others include collagen breakdown markers, proteolytic enzymes like matrix metalloproteinase 3 (MMP3), and bone turnover markers such as receptor activator of nuclear factor kappa ligand (RANKL).

A panel of proteomic biomarkers might also predict response to TNF inhibitors, FitzGerald says. 

In the meantime, the International Psoriasis and Arthritis Research team (IPART) based in Toronto has been tasked with developing research protocols.

“Some investigators are looking to do small-scale multicenter studies funded by industry, maybe 50 patients at each center, where they would collect MRI data to measure joint damage, as well as biomarkers, over a period of six months,” he says. “We will not see erosions by plain X-ray as early as six months. But MRI is more sensitive and will hopefully identify changes at the early six month period.”

BioDam plans to enroll as many as 1,000 PsA patients in a validation study at multiple sites across the world. They would be followed for two years to identify new erosions using X-rays (less expensive than MRI) of hands and feet at 12 month intervals.

Investigators would also collect patient questionnaires, blood and urine samples for analysis, and perhaps even DNA to explore potential genetic associations with erosive changes.