“Injectable Peptides” for Knee Arthritis? What the Sprifermin RCT Found

If you’ve heard about “injectable peptides” to regrow cartilage for knee arthritis, you’ve probably heard the name sprifermin. Sprifermin is a lab-made form of fibroblast growth factor-18 (FGF-18)—a signal that tells cartilage cells to grow. It’s injected directly into the knee joint. A large, well-run clinical trial looked at whether sprifermin can actually increase cartilage thickness and help symptoms in people with knee osteoarthritis.

The Study at a Glance (FORWARD Trial)

• Who was studied? 549 adults (median age 65) with symptomatic knee osteoarthritis (KL grade 2–3).

• What was tested? Injections into the knee of sprifermin at different doses and schedules versus placebo (salt water).

• Main outcome at 2 years: Change in total femorotibial cartilage thickness measured by quantitative MRI (an accurate way to measure cartilage).

• Key result: The highest dose (100 µg) increased cartilage thickness by ~0.05 mm more than placebo at 2 years. Lower doses didn’t outperform placebo. Symptoms (WOMAC pain/function/stiffness) were not better than placebo in any group.

How big is 0.05 mm?

It’s small—about half the thickness of a human hair. Importantly, there’s no established minimal clinically important difference (MCID) for cartilage thickness on MRI, so we don’t know whether a 0.05 mm gain is something patients can feel. The trial authors explicitly state the clinical importance is uncertain.

For context, observational research suggests people who go on to need a knee replacement tend to lose slightly more cartilage (on the order of a few hundredths of a millimeter over a couple of years) than those who don’t. Sprifermin’s 0.05 mm gain is in that same tiny range—but again, symptoms did not improve versus placebo in this RCT.

What about longer-term follow-up?

A 5-year follow-up analysis of the same trial reported that the structural benefit (the small cartilage increase) with the highest-dose sprifermin persisted through year 5. However, WOMAC pain scores improved by similar amounts in all groups, including placebo (a common pattern in injection trials), so no consistent symptom advantage was seen.

Did people feel better?

In the 2-year primary report, no—sprifermin did not beat placebo on the WOMAC (a standard knee pain and function questionnaire). For reference, the MCID for total WOMAC is roughly 7 points (or about 14% improvement). Sprifermin didn’t meet that benchmark versus placebo.

Is it safe?

Across groups, the rates and types of side effects were similar to placebo. The most common issues were temporary joint aches, swelling, or injection-site discomfort. Serious adverse events were not increased with sprifermin.

Is sprifermin FDA-approved?

No. As of today, sprifermin is not FDA-approved for knee osteoarthritis. Research is ongoing to determine whether structural changes translate into meaningful pain or function benefits for patients and whether they delay surgery.

Bottom line for patients

• What it does: At the right dose, sprifermin adds a very small amount of cartilage (about 0.05 mm) compared with placebo.

• What it doesn’t do (yet): In the RCT, it did not improve pain or function more than placebo over 2 years, and follow-up to 5 years still hasn’t shown a clear symptom advantage.

• What we still need: Trials that prove patients feel and function better and that structural gains change long-term outcomes (like delaying knee replacement).

• Practical take: For now, sprifermin remains investigational. Established options—exercise therapy, weight optimization, targeted physical therapy, NSAIDs (when appropriate), and selected injection strategies—remain the backbone of care.

References

1. Hochberg MC, Guermazi A, Guehring H, et al. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial. JAMA. 2019;322(14):1360-1370. doi:10.1001/jama.2019.14735. (Primary 2-year results: small structural gain; no symptom benefit; MCID for cartilage thickness unknown; WOMAC MCID ~7 points / 14%.) JAMA Network+2PMC+2

2. Eckstein F, Hochberg MC, Guehring H, et al. Long-term efficacy and safety of intra-articular sprifermin: 5-year FORWARD study results. Ann Rheum Dis. 2021;80(8):1062-1070. (Structural signal sustained to year 5; symptom improvements similar across groups.) BMJ Arthritis Care & Research

3. Eckstein F, et al. Cartilage thickness change by MRI and OA progression risk (FNIH OA Biomarkers Consortium). Osteoarthritis Cartilage. 2015;23(12):2194-2203. (Background on how tiny cartilage changes relate to progression risk.) PMC

4. Kim H, et al. State of OA drug development. Clin Transl Sci. 2022. (Sprifermin status in development; no current FDA approval.) PMC