Other “remarkable strategies” are emerging in the search for biomarkers, according to Dr. Rigby, who pointed to an article in the New England Journal of Medicine for an example.3 In that research, investigators looked at response of patients with melanoma treated with ipilimumab or tremelimumab. The malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were sequenced and characterized for their ability to predict clinical response. Their findings exemplify the potential of these approaches when they are applied to rheumatology, Dr. Rigby says.
Psoriatic arthritis is another type of rheumatologic disease in great need of a predictive biomarker, because skin psoriasis occurs many years before developing into psoriatic arthritis, Dr. Ruderman says. Only about 30% of people with skin psoriasis develop joint disease. “Right now, we can only watch it more carefully for when joint disease develops, but maybe we can then figure out what to do to prevent it from progressing if we could figure out who those people are.”
The search for biomarkers in rheumatic diseases may depend on some kind of breakthrough that is brought on by exome sequencing or by protein analysis or some other strategy. “The power of novel technologies is so striking and advancing so quickly that I think that it will happen. But I can’t decide whether these things are going to happen based on analyzing synovium from affected joints or some completely unexpected tissue in RA,” Dr. Rigby says.
“All of these things are out there. For the moment, the most encouraging thing for me is that the field is becoming increasingly rigorous, that questions are increasingly refined. First reports are always greeted with warmth and a certain amount of enthusiasm, but also with ‘let’s see it confirmed,’” he says.
Dr. Kremer says the Corrona registry, which has data on 40,000 patients with RA and psoriatic arthritis who are on biologic therapy, is looking at genetic or biomarker analyses on 2,800 of those patients. “Do we necessarily expect to find a smoking gun? That would be unrealistic, but if we can advance the ball down the field.”
Predicting Disease Progression
Biomarker research has shown results for a measurement of disease activity that helps predict the risk of future joint damage. Study of biomarkers in blood led to development and marketing of a composite test, Vectra DA (Crescendo Bioscience), which measures 12 serum proteins to provide a score on a scale of 1–100. The proteins, or biomarkers, included in the test are VCAM-1, EGF, VEGF-A, IL-6, TNF-R1, MMP-1, MMP-3, YKL-40, leptin, resistin, serum amyloid A and C-reactive protein (CRP). The Vectra DA score represents the level of RA disease activity and can provide objective information that is independent of CRP or conventional, physical exam-based measures.
