Updated 08 November 2016

Knee arthritis drugs beat placebos for pain, but with no clear winner

Injections rated slightly more effective at fighting knee pain than pills.


Pain-relieving treatments for knee arthritis all work better than doing nothing- but it's hard to point to a clear winner, new research concluded.

Using data from almost 140 studies, researchers found all of the widely used arthritis treatments - from over-the-counter painkillers to pain-relieving injections - brought more relief to aching knees over three months than did placebo pills.

But there were some surprises in the study, according to lead researcher Dr. Raveendhara Bannuru, of Tufts Medical Centre in Boston.

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Hyaluronic acid

Overall, the biggest benefit came from injections of hyaluronic acid (HA) - a treatment some professional medical groups consider only marginally effective.

Hyaluronic acid is a lubricating substance found naturally in the joints. Over the years, studies have been mixed as to whether injections of synthetic HA help arthritic joints, and the treatment remains under debate.

Bannuru cautioned that despite his team's positive findings, it's not clear whether hyaluronic acid itself deserves the credit.

That's because his team found a large "placebo effect" across the HA studies. Patients who received injections of an inactive substance often reported pain relief, too. As a whole, they did better than people in other trials who were given placebo pills.

According to Bannuru's team, that suggests there is something about the "delivery method" - injections into the knee joint, whatever the substance - that helps ease some people's pain.

But there's no clear explanation for why that would be, Bannuru said.

He and his colleagues report their findings in the Jan. 6 issue of Annals of Internal Medicine.

According to the U.S. Centres for Disease Control and Prevention, at least 27 million Americans have osteoarthritis - the "wear and tear" form of arthritis where the cartilage cushioning a joint breaks down. The knees are among the most commonly affected joints.

In the earlier stages of knee arthritis, doctors often recommend oral painkillers like acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Aleve).

Injections are another option - either with hyaluronic acid or the anti-inflammatory drug cortisone.

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Hard to compare

The problem is, few studies have actually tested any of those treatments head-to-head, Bannuru said. So it's hard to know whether one is any better than the others.

To get an idea, his team used a statistical method that allowed it to compare results from previous clinical trials that tested either oral medications or injections.

In general, the review found, all therapies were better than placebo pills at easing pain at the three-month mark. But they were not all equal.

Injections of hyaluronic acid were most effective, followed closely by cortisone. NSAIDs came in next, with acetaminophen rounding out the bottom of the list - which is not surprising, though it is important, Bannuru said.

He noted that acetaminophen is often the first painkiller of choice for arthritis, because NSAIDs are linked to increased risks of heart attack and stroke in older adults who take them long-term.

And because acetaminophen is less risky, it is still a "very reasonable" place to start, said Dr. Lisa Mandl, a rheumatologist at the Hospital for Special Surgery in New York City.

"However, I would suggest using a high dose for a short trial period. And if it's not effective quickly, move on to another option," said Mandl, who co-wrote an editorial published with the study.

And based on these findings, she said, injections - whether hyaluronic acid or cortisone - could well be worth a try. That's partly because they often work, but also because they can avoid the systemic side effects of oral painkillers, Mandl said.

With injections, side effects are usually limited to temporary pain and swelling. In rare cases, people can have an allergic reaction or infection, according to the American Academy of Orthopaedic Surgeons.

Bannuru said people with knee arthritis ultimately have to decide for themselves, after discussing the pros and cons of different therapies with their doctor.

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Options beyond drugs and injections

And there are options beyond oral drugs and injections.

"Even though we didn't test [them] in our study," Bannuru said, "it's important for people with knee arthritis to know there are several non-drug treatments, such as exercise and physical therapy."

Read More:
Physical therapy can be as good as knee surgery

Running won't raise risk of knee arthritis


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Professor Asgar Ali Kalla completed his MBChB (Bachelor of Medicine and Bachelor of Surgery) degree in 1975 at the University of Cape Town and his FRCP in 2003 in London. Professor Ali Kalla is the Isaac Albow Chair of Rheumatology at the University of Cape Town and also the Head of Division of Rheumatology at Groote Schuur Hospital. He has participated in a number of clinical trials for rheumatology and is active in community outreach. Prof Ali Kalla is an expert in Arthritis for Health24.

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