Scientists race to regrow lost knee cartilage

Bad knees sideline athletes and mere mortals alike.

About 14 million Americans have osteoarthritis of the knees severe enough to cause pain and inflammation, according to the Arthritis Foundation, and more people are getting the condition — also known as OA — as they age.

Kathleen Doheny, Medscape December 13, 2017

As the knee’s natural cushioning — the cartilage — wanes, inflammation and pain rise, and people can’t get around as well.

Building knee cartilage has been a dream of researchers, and now several methods are under study. None has yet shown it can prevent or cure osteoarthritis, and all are in early phases, caution the scientists who presented their findings at the recent annual meeting of the American College of Rheumatology in San Diego, CA.

Stopping Excess Bone Breakdown

A treatment known as MIV-711 targets an enzyme called cathepsin K that is thought to play a role in the destruction of cartilage and the breakdown of too much bone.

In adults, bones are constantly being broken down and built up or replaced to maintain a healthy skeleton. “This [treatment] stops the increased breakdown of bone that happens in OA,” says researcher Philip Conaghan, MD, a professor of musculoskeletal medicine at the University of Leeds in Great Britain. “It inhibits the cathepsin K.” The bone changes happen before the cartilage loss does, he says.

In the study, researchers assigned 244 men and women who have knee arthritis to get one of two oral doses of the treatment or a placebo pill for up to 28 days. The participants’ average age was 62, and many were overweight or obese.

The researchers did MRIs at the beginning of the study and at week 26 to find changes around the bone, which reflect cartilage change. They found 65% less bone disease progression in the treated groups, regardless of dose, Conaghan says.

But they found no less pain. “It did not help symptoms,” he says.

Stimulating Cartilage

Another treatment, sprifermin, is a type of human fibroblast growth factor, which plays a role in cell growth and tissue repair. “It stimulates the cells in the cartilage to make more cartilage,” says Marc Hochberg, MD, primary investigator of the study and head of rheumatology and clinical immunology at the University of Maryland School of Medicine.

He reported on the 2-year results of what will be a 5-year study. “The cartilage becomes thicker, and it will do a better job of shock absorption and it will slow the progression of already established knee OA,” he says.

Always warm up with a 5-minute walk first. Lie down when you’re ready to stretch your hamstring. Loop a bed sheet around your right foot. Use the sheet to help pull the straight leg up. Hold for 20 seconds, then lower the leg. Repeat twice. Then, switch legs.

The researchers assigned 549 men and women, ranging from age 40 to 85, to get three weekly shots of sprifermin in one of two doses or a placebo every 6 or 12 months.

Those in the groups treated with the higher dose of sprifermin had slightly more cartilage, about .03 millimeters in one area, but not all, as shown on MRI scans. Those in the placebo group lost about .02 millimeters over the same period, which Hochberg says is the natural progression of knee arthritis.

Pain scores fell a little in all groups, but the treated groups got no better pain relief than those getting a placebo. If future studies bear out these results, the ideal candidate for the treatment would be someone with early and mild arthritis of the knee, Hochberg says.

Stopping Cartilage Breakdown

Another treatment works with tissue regeneration and stops an enzyme from breaking down cartilage in the knee, says Yusuf Yazici, MD, chief medical officer of Samumed, a medical research and development firm. Yazici is also a clinical associate professor of medicine at New York University School of Medicine. With the treatment, he says, you restore the normal equilibrium in the knee by protecting it from cartilage breakdown.

He assigned 455 men and women, average age 60, to get one of three doses of the treatment or a placebo in a single shot in one knee.

The researchers did X-rays to see if the treatment made more space in the joint, which is a sign of more cartilage, Yazici says. “For the middle dose, in patients with one painful knee, it increased the joint space over placebo at 6 months and [it] further increased at 12,” he says. He says the people in this group were able to get around better and had less pain.

Perspective

Choosing which of the new treatments is most promising is difficult, says Brian Feeley, MD, an associate professor of sports medicine and orthopedic surgery at the University of California, San Francisco. He was not involved in the studies but reviewed the findings.

“The studies are all done slightly differently, so it’s hard to compare.” But, he says, so far, the improvement in some cases is very small.

Bottom line, for now? “Although the data does not show that these treatments are going to prevent or cure arthritis, the agents may be able to slow the progression of arthritis, which we don’t yet have the ability to do,” Feeley says.

Source Medscape

SAN DIEGO — At the American College of Rheumatology Annual Meeting, Marc C. Hochberg, MD, spoke about a study that evaluated the efficacy and safety of intra-articular sprifermin in patients with symptomatic radiographic knee osteoarthritis. When sprifermin was administered at a higher dose at 6 months or 12 months it slowed progression of joint space loss or cartilage thinning and was associated with an increase in cartilage thickness. Published on Healio November 14, 2017

References

Efficacy and Safety of Intra-Articular Sprifermin in Symptomatic Radiographic Knee Osteoarthritis: Results of the 2-Year Primary Analysis from a 5-Year Randomised, Placebo-Controlled, Phase II Study, Marc C. Hochberg, Ali Guermazi, Hans Guehring, Aida Aydemir, Stephen Wax, Patricia Fleuranceau-Morel, Asger Reinstrup Bihlet, Inger Byrjalsen, Jeppe Ragnar Andersen and Felix Eckstein. Abstract 1L, 2017 ACR/ARHP Annual Meeting October 19, 2017

oarsi_white_paper_oa_serious_disease_121416_1

Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration December 1, 2016 in Osteoaerthritis Research Society International, OARSI

Also see
Sprifermin may be effective in treatment of osteoarthritis Healio
New drug effective, well tolerated in patients with osteoarthritis knee pain Healio
A Study to Evaluate the Efficacy, Safety and Tolerability of MIV-711 in Osteoarthritis Patients ClinicalTrials.gov Identifier NCT02705625
MIV-711 phase IIa osteoarthritis study data presented as a late breaking poster at the Annual Meeting of the American College for Rheumatology Medivir
What’s New in Knee Osteoarthritis Treatments? WebMD