Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up

The upshot

For knee osteoarthritis, does a structured exercise and education program work better than a placebo injection one year later?

At 1 year, the GLAD exercise and education program and open-label placebo saline injections both produced only minor improvements with no meaningful difference between them. An exploratory finding suggests people who were taking pain medication at the start may benefit more from GLAD, but this needs confirmation.

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Primary study206 ParticipantsModerate evidence

Key points

Both groups improved only slightly in knee pain after 1 year, with no significant difference between them.
The between-group difference in KOOS pain was 1.5 points (95% CI -2.6 to 5.5), well below the 8-point threshold for a clinically meaningful change.
No differences were seen in any secondary outcome including function, quality of life, or global disease impact.
A large 33.5% loss to follow-up undermines confidence in the results.
An exploratory subgroup analysis hinted that patients using analgesics at baseline may benefit more from GLAD.

How it was conducted

Design: 1-year follow-up of an open-label, single-centre, randomized controlled trial (this extension was not pre-registered)
Participants: Adults 50 years or older with symptomatic, radiographically confirmed knee OA (Kellgren-Lawrence grade 2 or higher), BMI 35 or below, knee pain at least 4/10
Groups: 8-week GLAD exercise and education program vs open-label placebo of 4 intra-articular isotonic saline injections over 8 weeks
Primary outcome: Change from baseline in KOOS pain subscale at 1 year (intention-to-treat); MCID set at 8 points

What they found

KOOS pain change at 1 year: 8.4 points (SE 1.8) for GLAD vs 7.0 points (SE 1.7) for OLP; mean difference 1.5 points (95% CI -2.6 to 5.5), P = 0.48.
KOOS function change: -1.1 (95% CI -5.0 to 2.8), P = 0.56; KOOS quality of life change: 1.0 (95% CI -3.1 to 5.2), P = 0.62.
Patient Global Assessment change (VAS mm): mean difference -1.6 (95% CI -8.8 to 5.6), P = 0.66.
OMERACT-OARSI responders: 21 (20.6%) GLAD vs 18 (17.3%) OLP; OR 1.25 (95% CI 0.62 to 2.55), P = 0.53.
Exploratory subgroup: patients using analgesics at baseline favored GLAD by 9.9 KOOS pain points (95% CI 2.4 to 17.4, P = 0.0099).
Of 544 screened, 206 were randomized (102 GLAD, 104 OLP); only 137 provided 1-year data, with 69 participants (33.5%) lost to follow-up.

Limitations

Large attrition of about 30 to 40%, with only 137 of 206 randomized participants providing data at 1 year.
The 1-year follow-up was not part of the original a priori plan and was not registered.
Subgroup findings, including the analgesic-use result, were exploratory and require confirmation.
Single-centre, open-label design limits generalizability and allows expectation effects.

Why it matters

For patients: If you have knee osteoarthritis, a structured exercise and education program is likely to give about the same modest pain relief at one year as a placebo injection, so the broader health benefits of exercise are a reasonable reason to choose it.
For clinicians: Neither GLAD nor placebo saline showed superiority at 1 year, though patients already taking analgesics may be a subgroup worth watching in future trials.
For readers: This trial shows that much of the long-term benefit attributed to OA exercise programs may overlap with placebo response, but heavy dropout means the conclusion is not definitive.

Source

doi:10.1016/j.joca.2022.12.011

Read the original paper

Clinically assessing this area? See the knee special tests.