Likely Target of Next-Generation Arthritis Treatments

Can TNF inhibitors stop bone damage in psoriatic arthritis?

Posted 3/6/08

Researchers have learned more about how a leading drug prevents certain types of arthritis from eating away at bone, according to a study published in the March issue of Annals of the Rheumatic Diseases.

Psoriatric arthritis (PsA), like rheumatoid arthritis, is an autoimmune disease in which the body mistakenly attacks its own tissues. The attack comes in the form of inflammation and can result in bone erosions.

“In erosive psoriatic arthritis, mistaken immune signals tell osteoclasts to keep digging, as if they were trying to get at an infection buried inside the bone,” said Edward M. Schwarz, PhD, professor of Orthopaedics within the Center for Musculoskeletal Research at the University of Rochester Medical Center, and an author of the study.

Osteoclasts: Cells that rid the body of aging bone. Osteoblasts: Cells that form new bone.

In past studies, Schwarz and his team found an increased frequency of osteoclast precursors in the blood of patients with PsA. Past work has also shown that TNF blockers decrease osteoclast precursor frequency.

In the current study, researchers examined the molecular effects of the TNF inhibitor etanercept (Enbrel) in people with PsA. The research team took advantage of new imaging technology to show that the high level of osteoclast precursors seen in erosive arthritis originates in bone marrow lesions near affected joints.

Patients treated with anti-TNF therapy saw a dramatic drop in the median level of osteoclastic precursor cells (OCP) in their blood after 6 months of treatment. The rapid decline in OCPs after anti-TNF therapy provides one explanation for the anti-erosive effects of TNF blockade in PsA.

A second, related explanation may be seen in the bone marrow lesion results. The study found that the lesion volume decreased in 47 joints, indicating that the inflamed bone marrow was returning to normal. However, the analysis also revealed an increase in edema-like lesions in 31 joints at 6 months.

“A simple blood test can determine a person’s osteoclast precursor levels,” Schwarz said. “That should soon change medical practice as we can tell by OCP levels if a person has erosive disease. If those levels fail to drop immediately with anti-TNF therapy, that person is likely among the 30 percent of people who don’t respond to etanercept. We can spare them the side effects and perhaps switch them to drugs like rituximab or abatacept, which are approved for rheumatoid arthritis patients that do not respond to anti-TNF therapy. While the blood test can tell you if you have PsA, it cannot tell which joints are affected. That feat has been achieved in this study for the first time with new MRI technology, which shows which joints have pre-erosive, osteoclast precursor lesions forming in the nearby bone marrow. These two tests, done in serial fashion, should allow for earlier diagnosis and more precise treatment of psoriatic erosive arthritis.”