What are the next steps for a patient with unilateral right knee osteoarthritis who has already received Euflexxa (hyaluronic acid) injections?

Management After Euflexxa Injections for Knee Osteoarthritis

Do not continue hyaluronic acid injections—current major guidelines from the American Academy of Orthopaedic Surgeons and American College of Rheumatology/Arthritis Foundation conditionally recommend against routine use of hyaluronic acid for knee osteoarthritis due to inconsistent evidence and minimal clinical benefit. 1, 2

Critical Assessment of Prior Euflexxa Response

The pivotal decision depends on whether the patient experienced meaningful pain relief and functional improvement from the initial three-injection series:

If Patient Had Inadequate Response to Euflexxa:

• Stop viscosupplementation immediately and transition to intra-articular corticosteroid injections, which have Level 1B evidence from 19 high-quality and 6 moderate-quality studies demonstrating effective short-term pain relief 1, 2
• The number needed to treat for hyaluronic acid is 17 patients, meaning 16 patients receive no benefit for every 1 patient who does 1
• When limited to trials with low risk of bias, meta-analyses show that hyaluronic acid's effect size compared to saline injections approaches zero 1

If Patient Had Significant Benefit from Euflexxa:

• Re-injection could be considered based on documented response, though this contradicts general guideline recommendations 3
• Patients with Kellgren-Lawrence grade 3 osteoarthritis often demonstrate better response with a second series of hyaluronic acid injections compared to their first series 3
• Mean duration of symptom control is approximately 6 months (27 ± 7 weeks) between injection series 4
• However, corticosteroid injections remain the evidence-based standard and should be strongly considered even in responders 1, 2

Recommended Treatment Algorithm

First-Line Optimization (Must Be Implemented):

• Land-based exercise programs with joint-specific strengthening and range of motion exercises, which reduce pain and improve function with effect sizes ranging from -0.58 to 1.05 5, 2
• Weight loss if overweight, as this is recommended for virtually all patients with knee osteoarthritis 5, 2
• Physical therapy with structured rehabilitation protocols 1, 2
• Knee bracing for mechanical support, which has shown improvement in controlled studies 5, 2

Pharmacological Management:

• Intra-articular corticosteroid injections provide effective pain relief for up to 3 months with strong evidence (effect size 1.27 for pain relief over 7 days) 5, 1, 2
• Corticosteroids are particularly indicated for acute exacerbations, especially if accompanied by effusion 5
• Oral NSAIDs are strongly recommended when not contraindicated 2
• Topical NSAIDs as an alternative with fewer systemic side effects 1, 2
• Acetaminophen up to 3g daily in divided doses for additional pain control 1, 2

Treatments to Avoid:

• Do not use oral narcotics including tramadol, as they cause notable increase in adverse events without consistent improvement in pain or function 1, 2
• Do not proceed with arthroscopic debridement or partial meniscectomy for primary osteoarthritis, as it provides no benefit and delays definitive treatment 1
• Avoid using hyaluronic acid as "bridge therapy" when the patient has already failed appropriate conservative management 1

Important Caveats and Pitfalls

Guideline Evolution:

The evidence provided includes older EULAR guidelines from 2000-2003 5 that supported hyaluronic acid with Level 1B evidence for pain reduction and functional improvement, noting effect sizes of 0.04-0.9 for pain reduction over 60 days to one year 5. However, more recent high-quality guidelines from 2025 have reversed this recommendation based on rigorous meta-analyses limited to low-risk-of-bias trials 1, 2.

Radiographic Severity Considerations:

• Patients with Kellgren-Lawrence grade 2 demonstrate significantly greater positive response to hyaluronic acid compared to grade 3 patients 3
• Those with less severe radiographic changes benefit more from viscosupplementation 3
• Most trials investigating hyaluronic acid exclude severe osteoarthritis 5

When to Consider Total Knee Replacement:

• Refractory pain with radiological deterioration when conservative management has failed warrants referral for joint replacement 1
• No intra-articular injection will cause osteophytes to regress or cartilage to regenerate in patients with substantial and irreversible bone and cartilage damage 6

Cost-Effectiveness Concerns:

• Patients must be informed about the limited efficacy and cost-effectiveness of hyaluronic acid preparations 6
• The logistical burden of requiring 3-5 weekly injections with slower onset of action compared to corticosteroids (which provide relief within days) must be weighed against the potential for several months of benefit 5