11.13.2015

No effects on structural progression in 2-year randomized study

by Nancy Walsh
Senior Staff Writer, MedPage Today

SAN FRANCISCO — Intra-articular steroid injections are not effective over the long term for preventing structural damage in knee osteoarthritis, a 2-year randomized trial found.

In the study, which was funded by the National Institutes of Health, there were no significant differences between patients who received injections of triamcinolone hexacetonide every 12 weeks and those given placebo in change in pain on the Western Ontario and McMaster University Arthritis Index (WOMAC), with differences of -2.2 in the steroid group and -2.8 in the placebo group (P=0.3), reported Timothy E. McAlindon, MD, of Tufts University in Boston.

And while there were significantly greater changes on the Cartilage Damage Index (CDI) among patients in the steroid group compared with the placebo group, with changes per year of -52.1 in the steroid group and -17.8 in the placebo group (P=0.03), the difference was actually “tiny,” being only about 1%, and was of “uncertain clinical significance,” McAlindon said during a press conference at the annual meeting of the American College of Rheumatology here.

It’s now known that some degree of inflammation is present in the joint in osteoarthritis, and studies have suggested that the inflammation seems to predict structural progression, which raises the possibility that an intervention that reduces inflammation might delay the progression.

“Intra-articular corticosteroids are already in widespread use in the treatment of knee osteoarthritis, for short-term pain relief, but have never been tested specifically for effects on structural progression,” he said.

Another question is the safety of the procedure, because there have been case reports of patients who had repeated injections of cortisone into a joint and developed rapid structural progression, or analgesic arthropathy.

“To address those questions, we decided to test the hypothesis that intra-articular steroids might reduce structural progression in a randomized clinical trial using MRIs to look for structural changes,” he said.

The study included 140 patients, with slightly more than half being women. A third were nonwhite, and mean body mass index was 31.2 kg/m².

Participants had injections of 40 g triamcinolone or saline every 12 weeks, for a total of eight injections.

MRI cartilage damage was assessed using the validated quantitative CDI, which focuses on the regions of the joint that are most liable to damage. The area of denudation also was evaluated, and a semiquantitative feature score rated fissures, delamination, superficial fibrillation, and signal change.

As with pain on the WOMAC scale, similar findings were seen for the steroid and placebo groups for function, with changes in the triamcinolone group of -7.1 compared with -9.2 in the placebo group (P=0.4) and on the chair stand test (-1.1 versus -1.6, P=0.8).

The only structural endpoint other than the CDI that differed between the two groups was in the progression of superficial fibrillation, with more changes being seen in the placebo group (24% versus 11%, P=0.04). No differences were seen in total cartilage denudation, subchondral bone, or effusion volume.

“However, I think it’s salient that none of the structural differences seemed to translate into patient-reported outcome differences,” McAlindon said.

“I think we can conclude that intra-articular corticosteroids used at the dose of 40 mg for 2 years has no major effect on structure in the joint — either deleterious or beneficial — and that over the long-term we don’t see an overall effect on patient-reported outcomes or physical function,” he said.

A limitation of the study was the use of only one dose, and it’s possible that a larger dose might have had more of an effect, he said.

In addition, the study didn’t attempt to measure the short-term treatment benefits associated with intra-articular steroid injections, he noted.