Researchers have developed a tool to predict those at greatest risk for primary knee osteoarthritis (KOA) progression that incorporates using both genetic and clinical information, according to a study published online Jan. 7 in Rheumatology. By better identifying those likely to experience radiographic progression of joint degradation and the need for total knee replacement (TKR), this test may facilitate earlier diagnosis of joint destruction and enable early interventions intended to slow disease progression. The clinical outcomes of primary KOA are highly variable,” says lead author Francisco Blanco, M.D., in a statement. “Some patients may live for years without suffering significant loss of functional capability or evident radiologic progression. Instead, others may end up disabled or needing prosthetic surgery in a few years. In this, genetics play a key role: rapid progression of knee osteoarthritis is hereditary in 60 to 70 percent of all cases. Most older individuals show signs of OA. But, OA diagnosis remains based on symptomatic and radiographic presentation. Yet, the clinical course is “highly variable” and mean annual total direct costs for OA patients can be substantial, the authors report. So better prediction of those at risk for rapid progression could aid in optimizing clinical management of […]
Researchers have developed a tool to predict those at greatest risk for primary knee osteoarthritis (KOA) progression that incorporates using both genetic and clinical information, according to a study published online Jan. 7 in Rheumatology. By better identifying those likely to experience radiographic progression of joint degradation and the need for total knee replacement (TKR), this test may facilitate earlier diagnosis of joint destruction and enable early interventions intended to slow disease progression.
The clinical outcomes of primary KOA are highly variable,” says lead author Francisco Blanco, M.D., in a statement. “Some patients may live for years without suffering significant loss of functional capability or evident radiologic progression. Instead, others may end up disabled or needing prosthetic surgery in a few years. In this, genetics play a key role: rapid progression of knee osteoarthritis is hereditary in 60 to 70 percent of all cases.
Most older individuals show signs of OA. But, OA diagnosis remains based on symptomatic and radiographic presentation. Yet, the clinical course is “highly variable” and mean annual total direct costs for OA patients can be substantial, the authors report. So better prediction of those at risk for rapid progression could aid in optimizing clinical management of the disease by increasing the number of control office visits, and utilizing more expensive imaging evaluations for high-risk patients, while allowing low-risk patients to continue their usual physical activity.
Spanish researchers conducted a retrospective, multicenter study involving 220 KOA patients in the exploratory cohort (180 females and 40 males; mean age 61.3 years) and a replication cohort of 62 KOA patients (47 females and 15 males). Participants had a Kellgren–Lawrence (KL) grade 2 or 3 at the time of primary KOA diagnosis, with “progressors” defined as those whose KL grade increased to 4 or who were referred for total knee replacement within 8 years after diagnosis. Saliva or serum samples were collected for DNA isolation and genotyping using real-time polymerase chain reaction.
Older age at KOA diagnosis was the only clinical variable analyzed that was significantly associated with KOA progression (88 progressors in the exploratory cohort and 37 in the replication group). The researchers identified 23 single nucleotide polymorphisms significantly associated with KOA severe progression in the exploratory cohort. The predictive accuracy of the clinical variables alone was limited, but when genetic variables (eight single nucleotide polymorphisms) were added to the model, prediction significantly improved (area under the curve, 0.66 versus 0.82). The predictive ability for KOA progression of the full model was confirmed on the replication cohort.
Bioiberica Pharma is developing this tool, the Arthrotest, which has been available clinically in Spain since June 2013 (cost roughly $276). The company tells DTET that they are developing plans for expanded commercial access in Europe and the United States, with a U.S. replication study planned for this year. Bioiberica funded the study.
Takeaway: By incorporating genetic variants into a model with clinical variables (i.e. age) clinicians may be able to better predict which patients are at greatest risk for KOA progression, thereby personalizing disease management.
