One cycle of five intra-articular knee injections of sodium hyaluronate given in a single 8-week knee osteoarthritis treatment program efficiently reduces symptoms and is highly cost-effective.

Osteoarthritis (OA) of knee refers to a disabling condition causing progressive joint pain and dysfunction. It occurs as a result of damage to the articular cartilage, subchondral bone, synovitis, and osteophytes formation and is known to affect about 12% of population aged ≥60 years. Different conservative measures such as analgesics, aerobic training, and muscle strengthening were adopted initially to alleviate the symptoms of joint pain and dysfunction. Also, some surgical options for treating OA such as total knee arthroplasty (TKA) or unicompartmental knee arthroplasty are also available. Alternative nonsurgical choices for patients who failed to respond to conservative therapies are available that could decrease the knee pain, rebuild joint function, and likely limits the necessity for arthroplasty. One such nonsurgical measure is the use of intra-articular injections of hyaluronic acid (HA) or viscosupplementation. The recent meta-analysis has established the effectiveness of this nonsurgical treatment for knee OA over a follow-up period of 6 months. The clinical benefits of HA using conventional meta-analytic techniques are still undervalued due to differences occurring in control group effect sizes as suggested by the accumulated evidence. Intra-articular injections of exogenous HA replace OA-induced reductions in the concentration and molecular weight of endogenous HA, through postulated mechanisms including inhibition of chondrodegradative enzymes and inflammatory processes, stimulation of chondrocyte metabolism, and synthesis of articular cartilage matrix components. The major risk factor for knee OA development was chronic joint overload and while the treatment programs based on the synergy of joint uploading therapy and viscosupplementation can yield better results.

Rationale behind the research:

The clinical benefits of hyaluronate injections are undervalued. The present study was carried to address this great unmet need.

Objective:

To assess the efficacy and safety of nonsurgical intervention such as intraarticular injections of HA in patients with knee OA

Study outcome measures:

The study outcomes included:

• Knee pain severity: Knee pain severity was evaluated on a 0–10 Numeric Pain Rating Scale (NPRS) with higher values representing greater pain severity.
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores: The WOMAC was conducted to estimate knee OA-related pain, function, and stiffness. All WOMAC scores were changed to a 0–100 scale, with a higher score indicating a worse outcome. Responders were defined as patients with ≥30% improvement in NPRS and ≥20% improvement in WOMAC Pain and Function subscales.
• Other Outcomes: Current medication use and history of total knee arthroplasty base-case, subgroup, and sensitivity analyses were conducted to determine the incremental cost-effectiveness ratio (ICER) of the treatment program with comparisons to historical literature controls undergoing usual care.

Time Points:

• Treatment period: Baseline and 8 weeks
• Follow-up period: 3.7 years mean follow-up
  

Study outcomes

• Baseline: No significant baseline differences were observed between the groups
• Over the 8-week treatment period, knee pain NPRS decreased 66%, from 5.5±2.8 to 1.9±2.2 (p<0.001). At final follow-up, NPRS scores remained 60% below baseline and 75% of patients were considered NPRS responders (Fig. 1).
• All WOMAC subscores decreased 43%–49% during the 8-week treatment period. The clinical benefit associated with the multimodal knee OA treatment program was largely maintained over long-term follow-up. Compared to baseline, WOMAC subscale values remained 42% lower for pain, 41% lower for function, and 33% lower for stiffness.
• Routine medication use to alleviate knee OA symptoms was reported by 54.0% of patients, with NSAIDs (48.7%), opioids (8.1%), and cyclooxygenase 2 inhibitors (3.5%) most commonly reported
• TKA was performed in 22.8% (81/356) of knees during follow-up. No baseline patient characteristic had a statistically significant association with TKA risk although younger patients and those with greater radiographic disease severity had a tendency for elevated TKA risk.
• The multimodal knee OA treatment program was highly cost-effective with an ICER of $6,000 per QALY. Results of subgroup analyses, one-way deterministic sensitivity analyses, and second-order probabilistic sensitivity analyses resulted in ICERs ranging from $3,996 to $10,493 per QALY. The percentage of simulations with an ICER below willingness-to-pay limits was 97.2%, 98.9%, and 99.4% for the $50,000, $100,000, and $150,000 per QALY thresholds, respectively.

Figure 1: Decrease of knee pain NPRS from baseline over a 8 week treatment period

In patients with knee OA participated in a single 8-week program involving one cycle of five intra-articular knee injections of sodium hyaluronate given at weekly intervals, structured physical therapy, knee bracing, and patient education showed a clinical reduction in knee OA symptoms maintained over 3.7 years mean follow-up. This multimodal program was highly cost-effective over long range.

It was postulated that the economic burden due to knee OA would increase 50% by 2025, and the cost of knee procedures will increase by 3 million annually. The ideal therapy of OA should provide clinically meaningful improvements in pain and function, delay the need for TKA, and yield an ICER below the willingness-to-pay threshold and the establishment of pay-for-performance initiatives. All patients in this study lack functional improvement following >3 months conservative therapy before participating in the multimodal knee OA treatment program. This represents a protracted period between conservative care failure and TKA, defined as "knee OA treatment gap". In this gap phase, patient experienced debilitating pain, reduced quality of life, and significant financial burden. Non-surgical procedures like intra-articular injections once in a week for 5 weeks was considered as a viable therapeutic strategy to address the treatment gap in knee OA. The novel aspect of this study was clinical benefit, cost effectiveness and long follow up period in real-world settings.