Improved Pain and Function With Triamcinolone Acetonide Extended-Release and Cryoneurolysis for Knee Osteoarthritis: Use of a New Real-World Registry.

BACKGROUND: Knee osteoarthritis (OA) affects 19% of American adults aged more than 45 years and costs $27+ billion annually. A wide range of nonoperative treatment options are available. This study compared 6 treatments: cryoneurolysis with deep genicular nerve block (Cryo-Deep/Both), cryoneurolysis with superficial nerve block (Cryo-Superficial), intra-articular hyaluronic acid (IA-HA) injections, nonsteroidal anti-inflammatory drug injections (IA-NSAIDs), IA-corticosteroids (IA-CS) injections, or IA-triamcinolone extended release (IA-TA-ER) injections over 4 months for: (1) pain severity and analgesic use; and (2) physical function (from Knee Injury and Osteoarthritis Outcome Score for Joint Replacement). METHODS: Patients who had unilateral knee OA and received nonoperative intervention were enrolled in the Innovations in Genicular Outcomes Research registry, a novel, multicenter real-world registry, between September 2021 and February 2024. A total of 480 patients were enrolled. Both pain and functional outcomes were assessed at baseline, weekly, and monthly, which were analyzed by overall trend, magnitude changes pretreatment to post-treatment, and distribution-based minimally clinically important difference (MCID) score. Multivariate linear regressions with adjustments for 7 confounding factors were used to compare follow-up outcomes among 6 treatment groups. RESULTS: Use of IA-TA-ER injections was associated with the lowest pain, greatest pain reduction, and highest prevalence of patients achieving MCID relative to other treatments (P < .001). Deep/Both-Cryo and IA-CS were associated with a higher prevalence of achieving MCID than IA-HA, IA-NSAIDs, and Cryo-Superficial (P ≤ .001). Use of IA-TA-ER was also associated with the greatest functional score, improvement from baseline, and highest prevalence of patients achieving MCID than other treatments (P ≤ .003). CONCLUSIONS: The IA-TA-ER appears to outperform other treatments in terms of pain relief and functional improvement for up to 4 months following treatment. In addition, outcomes in the novel cryoneurolysis and conventional IA-CS were similar to one another and better than those in IA-HA and IA-NSAIDs.

Cryoneurolysis Associated With Improved Pain, Function, and Sleep in Patients Following total Knee Arthroplasty: Use of a New Real-World Registry.

BACKGROUND: Total knee arthroplasty (TKA) is performed on approximately 790,000 patients annually in the United States and is projected to increase to 1.5 million by 2050. This study aimed at assessing the use of preoperative cryoneurolysis on patients undergoing TKA by analyzing: (1) pain severity; (2) opioid use; (3) functional status; and (4) sleep disturbance (SD) over 6 months following discharge. METHODS: Patients enrolled in the Innovations in Genicular Outcomes Registry between September 2021 and February 2024 were followed for 6 months. Our analyses included patients undergoing unilateral primary TKA with no preoperative opioid prescription, who either received cryoneurolysis, or did not. Baseline patient demographics were collected before TKA and tabulated. Pain management was assessed via the Brief Pain Inventory-Short Form instrument for pain severity. SD was measured using the patient-reported outcomes measurement information system questionnaire. Each outcome measure was assessed prior to TKA, weekly, and at monthly follow-up. Data were analyzed by a generalized linear mixed-effect regression model to compare cryoneurolysis versus control patients, with a P < .05 as significant. RESULTS: There were 80 patients who were treated with preoperative cryoneurolysis, while 60 control patients did not have treatment. Patients receiving cryoneurolysis experienced significantly lower pain severity and SD over the 6-month follow-up than control patients (P = .046). Cryoneurolysis was also associated with a trend toward greater functional improvement that did not reach statistical significance (P = .061). Further, patients who underwent cryoneurolysis were 72% less likely than control group patients to take opioids over 6 months following discharge (P < .001). CONCLUSIONS: Preoperative cryoneurolysis therapy in opioid-naive patients undergoing TKA is associated with improved pain, decreased opioid use, and improved SD for 6 months postoperatively. Cryoneurolysis, a nonopioid pain relief modality administered preoperatively, demonstrated substantial benefits in patients who underwent TKA.

A Randomized, Multicenter, Double-Blind Study of Local Infiltration Analgesia with Liposomal Bupivacaine for Postsurgical Pain Following Total Knee Arthroplasty: Rationale and Design of the Pillar Trial.

INTRODUCTION: Liposomal bupivacaine, a prolonged-release formulation of bupivacaine hydrochloride, is indicated for infiltration into the surgical site for postsurgical analgesia. Results from previous total knee arthroplasty (TKA) studies suggest that analgesic efficacy associated with liposomal bupivacaine may be impacted by variability in infiltration technique. The PILLAR study is designed to assess liposomal bupivacaine efficacy in TKA using a standardized infiltration protocol. Materials and Methods/Design: This phase 4, multicenter, randomized, double-blind, controlled, parallel-group study will compare the safety and efficacy of infiltration with liposomal bupivacaine versus standard bupivacaine for postsurgical pain control in adults undergoing primary unilateral TKA. All subjects will receive a standardized pre-surgical analgesic regimen, and will be randomized to receive either liposomal bupivacaine 266 mg/20 mL (admixed with standard bupivacaine 0.5% 20 mL and expanded to a total volume of 120 mL) or bupivacaine 0.5% 20 mL (expanded to a total volume of 120 mL). The study drug will be infiltrated using six syringes (prefilled with 20 mL of study drug solution) to deliver 1-1.5 mL infusions into prespecified periarticular tissues. All subjects will receive standardized postsurgical analgesia and access to rescue medication. The co-primary efficacy endpoints are area under the curve of visual analog scale pain intensity scores from 12-48 hours postsurgery and total postsurgical opioid consumption from 0-48 hours. Secondary efficacy endpoints include other pain assessments, time to first use of rescue medication, discharge readiness, use of skilled nursing facilities, and hospital length of stay. Safety will be evaluated based on adverse events. DISCUSSION/CONCLUSION: The use of a standardized protocol comparing infiltration of equal volumes of the study drug, designed by experienced investigators to ensure complete coverage of all areas innervating the surgical site while minimizing leakage of study drug, will help define the role of liposomal bupivacaine in the setting of TKA.

Insights from Real-World Analysis of Treatment Patterns in Patients with Newly Diagnosed Knee Osteoarthritis.

BACKGROUND: Several nonpharmacologic and pharmacologic treatments are available for the management of knee osteoarthritis (OA)-related pain and for improving functionality; however, clinical guideline recommendations vary on their use. OBJECTIVE: To compare the treatment patterns in a real-world setting versus the guideline recommendations for the treatment of newly diagnosed patients with knee OA. METHODS: This retrospective analysis used data from the electronic health records of the Geisinger Health System between January 1, 2010, and December 2018 to identify adults with newly diagnosed knee OA who had not received previous therapy with intra-articular corticosteroids, opioids, intra-articular hyaluronic acid, or prescription nonsteroidal anti-inflammatory drugs (NSAIDs). Eligible patients were evaluated for the mutually exclusive treatment categories after diagnosis, including prescription NSAIDs, intra-articular corticosteroids, intra-articular hyaluronic acid (specifically an intra-articular bioengineered hyaluronic acid), opioids, physical therapy, bracing, and total knee arthroplasty. These 7 treatment categories were evaluated for utilization patterns in the real-world setting. RESULTS: A total of 8776 patients with a new diagnosis of knee OA were identified; 88.2% of them received 1 of the 7 evaluated treatments. The most frequently prescribed first treatment was intra-articular corticosteroids (26%), followed by opioids (17.6%), and intra-articular bioengineered hyaluronic acid (14.9%). The most often prescribed second treatment was opioids (15.8%), followed by physical therapy (14%), NSAIDs (11.8%), and intra-articular bioengineered hyaluronic acid (9.6%). Of note, 22.9% of the patients received only 1 evaluated therapy during the study period and did not receive a second treatment. CONCLUSIONS: Real-world treatment patterns in patients with newly diagnosed knee OA indicate that prescribers are using the spectrum of the available therapies that, at times, are different from the current treatment guideline recommendations.

Cost-Effectiveness of Treating Early to Moderate Stage Knee Osteoarthritis with Intra-articular Hyaluronic Acid Compared to Conservative Interventions.

INTRODUCTION: Evidence has demonstrated greater benefit of intra-articular hyaluronic acid (IA-HA) within earlier stages of knee osteoarthritis (OA) rather than waiting for patients to have progressed to later stages of disease progression. High molecular weight (HMW) HA has also been shown to be more effective than low molecular weight (LMW) HA products in mild to moderate knee OA, providing an important distinction to make within the class of IA-HA therapies. The purpose of this study is to evaluate the cost-effectiveness of treating patients with knee OA with HMW HA compared to LMW and conservative treatment, while taking into account disease stage. METHODS: Decision analytic models were created for early/moderate, as well as late stage knee OA. Models for late stage knee OA were created by assuming a range of response rates to IA-HA treatments from 10% to 50%. These models included conservative treatment using physical therapy/exercise, braces/orthosis, and medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. The models compared the cost per quality adjusted life year (QALY) gained for these treatments to the use of either LMW or HMW HA. Incremental cost-effectiveness ratios (ICERs) were calculated for each treatment in relation to HMW HA. RESULTS: When evaluating treatment in early to moderate knee OA, HMW HA was dominant over LMW HA and physical therapy/exercise, as it was less expensive and provided greater benefit. HMW HA was cost-effective versus braces/orthosis and NSAID/analgesic medications based on a willingness to pay threshold of $50,000. In the model of 50% response rate to IA-HA for late stage OA, HMW HA remained cost-effective in comparison to physical therapy/exercise and braces/orthosis at a willingness to pay threshold of $50,000; but not NSAID/analgesic medications. In the worst-case scenario of a 10% responder rate to IA-HA, HMW HA was no longer cost-effective in any circumstance. CONCLUSION: IA-HA, particularly HMW formulations, demonstrate cost-effectiveness when compared to conservative treatment options and LMW HA in patients with early/mid stage knee OA. The cost-effectiveness of HMW HA in patients with later stage knee OA was not as apparent, particularly because of the uncertainty in the proportion of patients with late stage OA who have a meaningful improvement after receiving IA-HA. This cost-effectiveness finding supports the use of IA-HA in patients with early and moderate knee OA, as the benefits of IA-HA are apparent within the patient population with mild to moderate knee OA. The findings of this study suggest that there is a potential cost savings benefit as a result of utilizing HMW HA in earlier stages of knee OA as opposed to later stages. FUNDING: Ferring Pharmaceuticals Inc.