Mean WOMAC Pain Research Articles

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

BackgroundWeight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.MethodsWe conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).ResultsA total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was −13.7% with semaglutide and −3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was −41.7 points with semaglutide and −27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.ConclusionsAmong participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.)

The Effect of Intra-articular Injection of Hypertonic Saline Versus Dextrose Prolotherapy for Knee Osteoarthritis

Background: Knee osteoarthritis (OA) is the most common chronic arthritis worldwide, often causing knee stiffness, pain, and functional impairment. This study aims to compare the effects of Dextrose prolotherapy and Hypertonic saline prolotherapy on knee pain, stiffness, and function in patients with knee OA. Methods: The study was conducted as a randomized clinical trial. Patients meeting radiological and clinical criteria for knee OA were sequentially contacted and provided written informed consent. Participants were randomly assigned to receive injections of Hypertonic saline (n = 30) or dextrose prolotherapy (n = 33). The primary outcome measure was clinical manifestations assessed using the compound score of the Western Ontario and McMaster University Arthritis Index (WOMAC). Results: Within-group analysis revealed significant differences in outcome scores for both treatments after 6 months. Both Hypertonic saline and dextrose prolotherapy showed significant improvements in the Visual Analog Scale (VAS), WOMAC composite score, pain, stiffness, and function. In the first month, VAS scores were higher with hypertonic saline compared to dextrose. Additionally, stiffness decreased more with dextrose than with hypertonic saline. After 6 months of treatment, although not statistically significant, hypertonic saline showed better outcomes in the mean WOMAC composite score and pain sub-score compared to dextrose. Conclusions: Among patients with knee OA, Hypertonic saline prolotherapy administered by a trained specialist yields safe and significant improvements in knee pain, stiffness, and function. Our results suggest no significant difference in VAS and WOMAC scores between hypertonic saline and dextrose prolotherapy.

The Effect of St. John's Wort Oil (Hypericum Perforatum L.) in Knee Osteoarthritis: A Randomized Controlled and Qualitative Study

BackgroundReducing pain and improving physical function are critical in the treatment of osteoarthritis. Although individuals use St. John's Wort oil to relieve pain due to osteoarthritis, no scientific research has been found investigating its effectiveness. AimThis study investigated the effect of St. John's Wort oil on pain intensity and physical functions in people with knee osteoarthritis. MethodsThis study adopted a single-blind, randomized, placebo-controlled, and qualitative mixed design. The sample consisted of 60 patients randomized into intervention (n = 30) and placebo control (n=30) groups. The experimental group participants were treated with topically St. John's Wort oil three times a week for 3 weeks, and the placebo control group participants were treated with olive oil three times a week for 3 weeks. Quantitative data were collected using a patient identification form, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Visual Analogue Scale. Qualitative data were collected through semi-structured interviews. ResultsThe experimental group had a significantly lower mean Visual Analog Scale score in the first, third, and fourth follow-ups than the control group. The experimental group had significantly lower mean WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function subscale scores in the last follow-up than in the first follow-up. The qualitative data agreed with the quantitative data. ConclusionsThe results show that St. John's Wort oil helps people with knee osteoarthritis feel less pain and become physically more active. Additional research is warranted to better understand the effect of St. John's Wort oil on pain intensity and physical functions in people with knee osteoarthritis.

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers

PurposeTo characterize the safety, efficacy, and potential role of genicular artery embolization (GAE) as a disease-modifying treatment for symptomatic knee osteoarthritis (OA). Materials and MethodsThis is an interim analysis of a prospective, single-arm clinical trial of patients with symptomatic knee OA who failed conservative therapy for greater than 3 months. Sixteen patients who underwent GAE using 250-μm microspheres and had at least 1 month of follow-up were included. Six patients completed the 12-month follow-up, and 10 patients remain enrolled. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was evaluated at baseline and at 1, 3, and 12 months. Serum and plasma samples were collected for biomarker analysis. The primary end point was the percentage of patients who achieved the minimal clinically important difference (MCID) for WOMAC pain score at 12 months. Baseline and follow-up outcomes were analyzed using the Wilcoxon matched-pairs signed-rank test. ResultsTechnical success of the procedure was 100%, with no major adverse events. The MCID was achieved in 5 of the 6 (83%) patients at 12 months. The mean WOMAC pain score decreased from 8.6 ± 2.7 at baseline to 4.9 ± 2.7 (P = .001), 4.4 ± 2.8 (P < .001), and 4.7 ± 2.7 (P = .094) at 1, 3, and 12 months, respectively. There was a statistically significant decrease in nerve growth factor (NGF) levels at 12 months. The remaining 8 biomarkers showed no significant change at 12 months. ConclusionsGAE is a safe and efficacious treatment for symptomatic knee OA. Decreased NGF levels after GAE may contribute to pain reduction and slowing of cartilage degeneration.

Association of adipokines with severity of knee osteoarthritis assessed clinically and on magnetic resonance imaging

ObjectivesWe aimed to evaluate the association between the adipokines: Leptin, Adiponectin, Resistin, and high sensitive-C-reactive protein (hs-CRP) with clinical, radiographical and magnetic resonance imaging (MRI) assessment of knee osteoarthritis (OA) severity. DesignWe performed a cross-sectional study in participants with earlier knee OA. Demographics, clinical (WOMAC), radiographical and MRI (BLOKS scoring) severity of knee OA were assessed. Serum leptin, adiponectin, resistin and hs-CRP were measured. Association of adipokines and hs-CRP with clinical, radiographic and MRI severity outcomes were evaluated using regression models with adjustment with age, sex, and body mass index (BMI). Results137 participants with earlier knee OA (82% women, mean ​± ​SD age: 55.5 ​± ​7.8 years) were included. Participants had moderate knee OA symptoms, mean WOMAC pain and function were 30.6 ​± ​18.0, and 31.7 ​± ​19.8 respectively. Mean BMI was 27.0 ​± ​5.9 ​kg/m2. After adjustment with age, sex and BMI, serum leptin was positively associated with osteophyte size, cartilage integrity, infrapatellar synovitis and effusion. While hs-CRP was associated with meniscus extrusion and adiponectin was associated with WOMAC pain and function. ConclusionSerum adipokines, particularly leptin was associated with severity of various structural defects of the knee joint on MRI beyond age, sex and BMI in earlier knee OA.

The impact of primary patella resurfacing on health-related quality of life outcomes and return to sport in total knee arthroplasty (TKA).

Primary patella resurfacing (PPR) in primary total knee arthroplasty (TKA) is a topic without clear clinical evidence. Using Patient Reported Outcome Measurements (PROM), previous work found TKA patients without PPR to have more pain postoperatively, but little is known whether this may impede patients from returning to their usual leisure sport. This observational study aimed at evaluating the treatment effect of PPR, with PROMs and return to sport (RTS). 156 primary TKA patients were retrospectively included from August 2019 to November 2020, from a single hospital in Germany. PROMs were measured with the Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the EuroQoL Visual Analog Scale (EQ-VAS), preoperatively and 1year postoperatively. Leisure sport with three levels of intensity (never, sometimes, regular) were requested. The treatment effect of PPR was evaluated with a difference-in-difference (DiD) approach, with several confounders. Descriptively, the mean WOMAC total score and the mean WOMAC pain score were postoperatively better with PPR, ( - 4.8 points, - 1.1 points), then without PPR. The mean improvements of the WOMAC total score were better with PPR ( - 7.8 points). Mean improvements for the WOMAC pain score were also better with PPR ( - 1.2 points). Mean EQ-VAS were postoperatively similar, and the mean improvements were better with PPR (3.4 points). Rate of RTS was 93% for patients with PPR and 95% for patients without PPR. The DiD revealed minor differences in PROMs and RTS, not to result in statistically significant treatment effects. There was no treatment effect for TKA with PPR, regarding PROMs and RTS, and descriptive differences were below published thresholds for clinical relevance. Rate of RTS was high for all patients, regardless of PPR. For the two endpoint categories, there was no measurable advantage of TKA with PPR over TKA without PPR.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity

Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. ClinicalTrials.gov Identifier: NCT02577549.

OUTCOME OF USING PLATELET, PLASMA AND GROWTH FACTORS AS AN ORTHOBIOLOGIC DERIVATIVE TO AVOID INVASIVE SURGICAL PROCEDURES FOR TREATING KNEE OSTEOARTHRITIS AMONG ELDERLY PATIENTS

Background: The application of platelet, plasma and growth factors (PP&amp;GF) is an intra-articular orthobiologic intervention that has been proven to be safe, having less systemic complications compared with conventional treatments and could constitute an option for treating elderly patients with knee osteoarthritis (OA). However, an intermediate result of using PP&amp;GF has yet to be well established.&#x0D; Objectives: This study aimed to report the survival analysis of 24-month follow-up treatment using PP&amp;GF among elderly patients with knee OA as primary outcome. The secondary outcomes were functional improvement in terms of international knee documentation committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score and visual analog scale (VAS) pain score.&#x0D; Methods: A prospective cohort study was performed among patients with knee OA (Kellgren and Lawrence (KL) grade I-IV), aged more than 65 years who did not respond to conservative treatments. All patients received intra-articular PP&amp;GF treatment and were followed up to 24 months. Primary outcome was recorded as any surgical treatment at any time point post-PP&amp;GF injection. Secondary outcomes including IKDC, WOMAC and VAS pain score were also assessed.&#x0D; Results: A total of 184 participants were enrolled in this study. The overall survival rate of patients not undergoing any surgical procedures during 24-month follow-up was 87.50%±2.44%. The mean IKDC, WOMAC and VAS pain scores were 39.59±0.58, 55.9±1.09 and 6.63±0.13, respectively at baseline while those at 24-month follow-up were 46.77±0.81, 38.32±1.33 and 4.92±0.13, respectively. The mean platelet concentrations before and after centrifugation were 1.85x105 cells/μL (1.20-3.36x105 cells/μL) and 1.4x106 cells/μL (5.80x105-3.5 x106) cells/μL, respectively, which showed final PP&amp;GF products contained 6-10 times higher platelet concentration than those in the peripheral blood.&#x0D; Conclusion: Intra-articular injection of PP&amp;GF is a potential treatment for severe knee OA especially among elderly patients. This method provided 87.50% survivorship from surgical intervention at 24-month follow-up. Most patients improved both pain and functional outcomes. We propose that the optimal preparation technique for PP&amp;GF is the key step for improving patients’ clinical outcomes and regaining their quality of lives.

Nortriptyline for pain in knee osteoarthritis: a double-blind randomised controlled trial in New Zealand general practice.

BackgroundOsteoarthritis (OA) of the knee is a common cause of chronic pain. Analgesics that are currently available have limited efficacy and may be poorly tolerated. Tricyclic antidepressants are used as analgesics for other chronic conditions, but they have not been evaluated as analgesics in OA.AimTo investigate the analgesic efficacy of nortriptyline in people with knee OA.Design and settingA two-arm, parallel-group, 1:1, double-blind, randomised, placebo-controlled trial in Christchurch, New Zealand.MethodParticipants were recruited from orthopaedic outpatient clinics, primary care, and through public advertising. Adults with knee OA and a pain score of ≥20 points on the 50-point Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale were randomised to receive either nortriptyline or identical placebo for 14 weeks. The primary outcome was knee pain at 14 weeks measured using the WOMAC pain subscale. Secondary outcomes included: function; stiffness; non-steroidal anti-inflammatory drug, opioid, and/or paracetamol use; each participant’s global assessment; and adverse effects at 14 weeks.ResultsOf the 205 randomised participants, 201 (98.0%) completed follow-up at 14 weeks. The baseline-adjusted mean WOMAC pain subscale score at week 14 was 6.2 points lower (95% confidence interval = −0.26 to 12.6, P = 0.06) in the nortriptyline arm versus the placebo arm. Differences in secondary outcomes generally favoured the nortriptyline arm, but were small and unlikely to be clinically relevant. However, the following were all more commonly reported by participants taking nortriptyline than those taking a placebo: dry mouth (86.9% versus 51.0%, respectively, P<0.001), constipation (58.6% versus 30.4%, respectively, P<0.001), and sweating (31.3% versus 20.6%, respectively, P = 0.033).ConclusionThis study suggests nortriptyline does not significantly reduce pain in people with knee OA. The adverse effect profile was as expected.

A prospective study to evaluate tibial plateau fractures functional outcome treated by locking compression plate in a tertiary care centre, South India

Background: Knee joint is the major weight bearing joints in the lower extremity. Proximal tibial fractures are commonest intra-articular fractures. As more and more concepts about biological fixation become clearer the innovation of plates progressed and lead to the development of less invasive stabilizing system. This new system is technically mature as it offers numerous fixation possibilities and has proven to worth in complex fracture situations and in osteoporotic bones. Objectives:To evaluate functional outcome following three column locking compression plate reconstruction for treating tibial plateau fractures in a tertiary care centre in South India. Methods:This study was a prospective study done on 34 consenting cases of proximal tibial fractures admitted to the Department of Orthopaedics, and underwent surgical treatment for tibial plateau fractures at MS Ramaiah Hospitals, Bengaluru. The patients were chosen based on the inclusion and exclusion criteria. Results were evaluated by fracture union on X ray and descriptive statistics were used to analyze the data. Results: In the present males were, 97%, most patients belonged to the category 40-50 years (14 patients, 41.18%). The mean age was 39 years. Vehicular accident (27 patients, 79%). right sided injury (24 patients, 69.38%), type of Schatzker's fracture type VI (29 patients, 85.2%), followed by Type IV 4 patients 11.76%. Mean WOMAC pain, stiffness and functional limitation score were 15.706 and 12.706, 5.8. and 3.7 and 66.7 and 53.7 in the preoperative and the post-operative period respectively and was statistically significant. Conclusion: Three-column fixation is a new fixation concept in treating complex tibial plateau fractures, which is especially useful for multiplanar fractures involving the posterior column. The combination of posterior and anterior-lateral approaches is a safe and effective way to have direct reduction and satisfactory fixation for such difficult tibial plateau fractures.

Evaluation of results of arthroscopic debridement and lavage with injection of hylan polymer in the management of osteoarthritis of knee

Objective: An evaluation of safety and efficacy of high molecular weight hyaluronic acid (HA) delivered at the time of arthroscopic debridement of the osteoarthritic knee. Methods: Thirty-four consecutive patients who met inclusion and exclusion criteria underwent arthroscopic debridement by a single surgeon and concomitant delivery of 6 ml/90 mg HA. These patients were evaluated preoperatively, at 3 months, 6 months and 9 months postoperatively. Evaluations consisted of WOMAC pain score and complications. Results: No complications occurred during this study. Pre-op average mean WOMAC pain score was 65.050 (n = 34) and 80.544 at 3 months (n = 34). Final average WOMAC pain score improved to 79.994 at six months (n = 34). No patients had deterioration of the WOMAC pain score. Conclusion: The results show that concomitant delivery of high molecular weight hyaluronan is safe when given at the time of arthroscopic debridement of the osteoarthritic knee. By delivering HA at the time of the arthroscopic debridement, there may be a decreased risk of joint infection and/or injection site pain. Furthermore, the combination of both procedures show efficacy in change of WOMAC pain scores.

Gonartrozlu Yaşlı Hastada D Vitamininin Kas Gücü ve Fonksiyonel Durum Üzerine Etkisi

Introductıon: The aim of this study was to evaluate the effects of vitamin D levels on pain intensity, muscle strength and functional status of elderly patients with osteoarthritis of the knee. &#x0D; Methods: Eighty one patients with osteoarthritis of the knee were enrolled in this study. The pain was measured with visual analogue scale (VAS). Western Ontario and McMaster University Arthritis Index (WOMAC) was used to evaluate pain, stiffness, and physical function. The maximum isokinetic muscle strength and the peak torque/body weight values were measured. &#x0D; Results: The patients were divided into two groups according to their 25 (OH) vitamin D levels: Group 1 consisted of patients whose 25 (OH) vitamin D levels were below 20 ng/ml and Group 2 comprised those with levels above 20 ng/ml. The VAS scores, the mean WOMAC pain, function and total scores were higher in Group 1 than Group 2. The maximal isokinetic muscle strength of extensor and flexor muscles of the knee and the peak torque/body weight values were significantly lower in Group 1 than in Group 2 (p

Fitbit Analysis Shows Enhanced Mobility Of Knee Osteoarthritis Patients Treated With Triamcinolone Acetonide Extended Release

PURPOSE: In knee osteoarthritis (OAK), walking >6000 steps/day can prevent functional limitation (White DK. Arthritis Care Res. 2014;66:1328). Intra-articular triamcinolone acetonide extended-release (TA-ER) is approved for OAK pain. This Phase 3b study assessed safety and an exploratory endpoint of mobility (steps/day) in patients treated with TA-ER. METHODS: OAK patients aged ≥40 years, symptomatic ≥6 months, with Western Ontario and McMaster Universities Osteoarthritis Index pain (WOMAC-A) score ≥6, and index-knee pain >15 days during the past month received TA-ER on Day 1. Movements were analyzed with a Fitbit® device (≥7 days prior to Day 1 to end of Week 12). RESULTS: A total of 208 patients were treated with TA-ER; 67.8% had moderate-severe OAK, mean age of 60.8 years, and mean body mass index (BMI) of 31.4 kg/m2. Baseline mean WOMAC pain score was 2.17. Mobility improved as seen by increases in weekly mean steps/day. 73 of 203 patients (36%) with sufficient step data at baseline had <6000 steps. Of these, 42 (57.5%) had ≥1 post-baseline week with average daily steps >6000; 19 (26.0%) had ≥50% of their follow-up with >6000 steps. Patients treated with TA-ER had mean changes from baseline in WOMAC pain scores of −1.4, −1.2, and −0.8 at Weeks 4, 8, and 12, respectively. A significantly greater change in steps from baseline was associated with decreases in WOMAC pain scores, male sex, lower BMI, lower baseline GPAQ average MET, and lower baseline steps/day. For every 1-unit decrease (from baseline) in mean WOMAC pain, mean steps/day increased by 339 (Figure 1). CONCLUSIONS: OAK patients given TA-ER had increased mobility (≥6000 steps/day) as measured by fitness monitor which was associated with a decrease in pain. Limitations were incomplete adherence to monitor usage and a no comparator open-label design. Fitness monitors are a feasible tool to measure patient mobility and understand pain and function.

Osteoarthritis physical activity care pathway (OA-PCP): results of a feasibility trial

BackgroundTo obtain information on feasibility and acceptability, as well as preliminary data on efficacy, of an Osteoarthritis Physical activity Care Pathway (OA-PCP).MethodsThis was a single group pilot study involving 60 participants with symptomatic, physician diagnosed knee or hip OA, recruited from primary care clinics. Participants self-reported completing less than 150 min per week of moderate-to-vigorous physical activity (MVPA) at baseline. The 3-month OA-PCP intervention involved 3 physical activity (PA) coaching calls (focused on goal setting), three check-in emails and linkage with community-based or online resources to support PA. Efficacy outcomes were collected at baseline and 4-month follow-up. The primary efficacy outcome was minutes of MVPA, assessed via accelerometer. Secondary outcomes included minutes of light intensity activity, sedentary minutes, step counts, and Western Ontario and McMaster Universities (WOMAC) pain and function subscales. Participants were also asked to rate the helpfulness of the OA-PCP intervention on a scale of 0–10. Differences in efficacy outcomes between baseline and 4-month follow-up were assessed using paired t-tests.ResultsAmong participants beginning the study, 88% completed follow-up assessments and ≥ 90% completed each of the intervention calls. Average daily minutes of MVPA was 8.0 at baseline (standard deviation (SD) = 9.9) and 8.9 at follow-up (SD = 12.1, p = 0.515). There were no statistically significant changes in light intensity activity, sedentary time or step counts. The mean WOMAC pain score improved from 8.1 (SD = 3.6) at baseline to 6.2 (SD = 3.8) at follow-up (p < 0.001); the mean WOMAC function score improved from 26.2 (SD = 13.2) to 20.2 (SD = 12.5; p < 0.001). The mean rating of helpfulness was 7.6 (SD = 2.5).ConclusionsResults supported the feasibility and acceptability of the study, and participants reported clinically relevant improvements in pain and function. PA metrics did not improve substantially. Based on these results and participant feedback, modifications including enhanced self-monitoring are being made to increase the impact of the OA-PCP intervention on PA behavior.Trial registrationNCT03780400, December 19, 2018.

Safety, tolerability, pharmacokinetics, and clinical outcomes following treatment of painful knee osteoarthritis with senolytic molecule UBX0101

Purpose: To report the Results of a Phase 1 study that assessed the safety, pharmacokinetics (PK), and clinical outcomes of single dose, intra-articular (IA) UBX0101 in patients (pts) with painful knee osteoarthritis (OA). In a previous observational biomarker study of patients with painful knee OA, the percentage of senescent cells (SnCs) in synovial biopsies positively correlated with disease severity, synovitis severity, and knee pain. UBX0101 is an MDM2/p53 interaction inhibitor that can induce apoptosis of senescent synovial fibroblasts. Reducing the number of SnCs from painful OA joints with UBX0101 may reduce pain and create a pro-regenerative environment. Methods: This was a Phase 1, double-blind, randomized, placebo-controlled, single, ascending dose (SAD) study in 48 pts randomized 3:1 to IA UBX0101 (dose range of 0.1 to 4.0 mg) or placebo IA. Key eligibility criteria included knee OA by ACR criteria, Kellgren-Lawrence (KL) grade 1-4, and mean daily pain between 4-9 on a Numeric Rating Scale (NRS, 0-10). Clinical outcomes through 12 weeks included NRS and total WOMAC with pain, function, and stiffness sub-scores derived from the Knee Injury and Osteoarthritis Outcome Score (KOOS) Survey. PK modeling was used to pre-define low (0.1 to 0.4 mg) and high (1.0 to 4.0 mg) dose groups, predicted to achieve knee concentrations below and above 50% effective concentration (EC50) pharmacological thresholds for senolysis, respectively. The SAD study design and sample size were chosen for evaluation of safety. Statistical significance for efficacy endpoints in this Phase 1 SAD study size was considered to be p<0.1. WOMAC sub-scores were item-averaged (i.e., each was normalized to a 0-4 Likert scale). A minimal clinically important difference (MCID) for the WOMAC pain sub-score was considered to be a within-subject reduction in the pain sub-score of ≥0.5. In addition, the rate and extent of pain reduction was determined using the area under the effect curve (AUC) for both NRS and WOMAC pain sub-score. Odds ratios for achieving response were determined using logistic regression models controlling for baseline NRS score and baseline WOMAC sub-score. Results: The SAD study population was balanced regarding patient characteristics and baseline outcome measure values; mean age was 62 years, 67% were female, 89.6% white, mean WOMAC pain sub-score at baseline was 1.96 ± 0.46. Single IA doses of UBX0101 up to 4 mg were well-tolerated. Most adverse events (AEs) were mild. No serious AEs occurred and no AEs led to discontinuation. The plasma PK of UBX0101 following single IA injection demonstrated minor inter-patient variability at all dose groups and systemic concentrations were low and further minimized by an estimated 4-hour elimination half-life. Improvements in pain and function were dose-dependent, clinically meaningful, and durable through 12 weeks for the high doses group of UBX0101 (table). Greater proportions of pts in the high doses group achieved decreases from baseline in the WOMAC pain sub-score equivalent to the MCID, and twice the MCID, at Week 12 compared to the placebo and low dose groups. The odds ratio of 3.68 versus placebo of having a 70% reduction from baseline in the WOMAC pain sub-score in the high doses group was nearly statistically significant (p=0.106, alpha=0.1). The magnitude and duration of pain reduction as measured by the mean (standard deviation) WOMAC pain AUC from baseline to Week 12 was 4.94 (3.66) in the high doses group (p=0.034 vs placebo), 3.32 (3.62) in the low doses group, and 2.28 (2.35) in the placebo group. Conclusions: Single IA doses of UBX0101 up to 4.0 mg were well-tolerated by patients with painful knee OA. Systemic exposure was well described by a one-compartment model with first order absorption. The activity of UBX0101 is supported by the dose-dependent, clinically meaningful, and durable improvements in pain and function observed. Senolysis with IA UBX0101 may be an important future therapeutic option for pts with knee OA.Tabled 1Clinical Outcomes at Week 12UBX0101EndpointPlaceboInjection(n=14)Low doses,0.1-0.4mg (n=16)High doses,1.0-4.0mg (n=18)WOMAC Pain (0-4)Baseline, mean1.872.141.86LSM Change from BL to Week 12 (95% CI)-0.74 (-1.14, -0.34)-0.49 (-0.89, -0.10)-1.09 (-1.38, -0.80)p-value0.430.07Mean Daily Pain NRS (0-10)Baseline, mean6.476.296.31LSM Change from BL to Week 12 (95% CI)-1.96 (-3.14, -0.77)-2.66 (-3.78, -1.55)-3.95 (-4.74, -3.16)p-value0.42<0.01WOMAC Function (0-4)Baseline, mean1.932.051.94LSM Change from BL to Week 12 (95% CI)-0.72 (-1.12, -0.31)-0.49 (-0.88, -0.10)-1.05 (-1.36, -0.74)p-value0.430.13WOMAC= Western Ontario and McMasters Universities Osteoarthritis Index (Likert) 0-4, LSM= Least-squares mean, BL=Baseline, CI=Confidence Interval, NRS=Numeric rating scale 0-10 Open table in a new tab WOMAC= Western Ontario and McMasters Universities Osteoarthritis Index (Likert) 0-4, LSM= Least-squares mean, BL=Baseline, CI=Confidence Interval, NRS=Numeric rating scale 0-10

A clinical study to evaluate efficacy and safety of AHPL/AYTAB/0313 tablet in subjects suffering from osteoarthritis of knee(s).

Background:Osteoarthritis (OA) is the most common form of arthritis with unsatisfactory treatment outcomes.Objectives:To evaluate efficacy and safety of AHPL/AYTAB/0313 tablet in subjects with OA of knee joint.Study Design:Prospective, open-label, single-arm clinical study conducted in daily clinical practice setting.Method:Subjects were advised to take 2 AHPL/AYTAB/0313 tablets twice daily orally after meals for 180 days. 48 subjects completed the study. The primary endpoints were changes in mean visual analogue scale (VAS) pain score and WOMAC score. Secondary endpoints were quality of life, time to walk 50 feet, knee joint swelling, use of analgesic drug as rescue medicine, and safety parameters.Results:At baseline visit, the mean index knee joint pain (VAS) score was 82.29 ± 15.19, which reduced significantly to 19.38 ± 13.75 on day 180. The mean WOMAC combined score at baseline was 39.94 ± 11.67, which reduced significantly to 09.58 ± 05.77 (76.0%) on day 180. The mean WOMAC pain score at baseline was 09.65 ± 02.91, which reduced significantly to 02.06 ± 01.46 on day 180. The mean WOMAC stiffness score at baseline was 03.48 ± 01.58, which reduced significantly to 00.63 ± 01.08 on day 180. The mean WOMAC difficulty score at baseline was 26.81 ± 09.63, which reduced significantly to 06.90 ± 04.78 on day 180. The mean walking time to walk 50 feet reduced significantly by 40% on day 180. Not a single subject was known to have knee joint swelling from 150 days onwards. Only 5 subjects were using analgesic as rescue medicine on day 180. Twenty-six subjects had adverse events (AEs). Most of the AEs were not associated with the study medication. Vitals and all the safety laboratory parameters were within normal limits both at baseline and on day 180.Conclusion:“AHPL/AYTOP/0113” tablet is safe and significantly effective in reducing pain, swelling, and stiffness of knee joints and improving mobility of knee joints in patients with OA. CTRI registration No. is CTRI/2015/09/006177.

Effect of medial meniscus extrusion on arthroscopic surgery outcome in the osteoarthritic knee associated with medial meniscus tear: a minimum 4-year follow-up.

Background:The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up.Methods:This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model.Results:Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD −0.630, 95% CI: −1.250, −0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022).Conclusions:Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.

Lack of evidence that beta blocker use reduces knee pain, areas of joint pain, or analgesic use among individuals with symptomatic knee osteoarthritis

The potential for beta blocker use to reduce joint pain and analgesic use in osteoarthritis (OA) patients has not been well established. The objective of this study was to estimate the association between beta blocker use and knee pain, areas of joint pain, and analgesic use among participants with symptomatic knee OA. We selected participants with symptomatic knee OA from the Osteoarthritis Initiative. Outcome measures included knee pain (e.g., WOMAC pain subscale), areas of joint pain (e.g., widespread joint pain), and analgesic use (e.g., use of strong pain prescriptions including opioids). We decomposed time-varying beta blocker use into within-person and between-person variation, and included these components in linear mixed effects models for repeated outcome measures of knee pain, joint pain, and analgesic use over 8 years. Among 1,168 participants, 15% reported beta blocker use at baseline. Beta blocker users (5.2, 95% CI [4.7, 5.8]) had similar estimated mean WOMAC pain scores as other anti-hypertensive users (4.9, 95% CI [4.6, 5.2]), with an estimated within-person difference of 0.1 (95% CI [-0.3, 0.4]). Proportion of participants reporting widespread joint pain was similar between beta blocker users and other anti-hypertensive users (40.1% vs 40.3%; within-person effect, odds ratio [OR]=0.87, 95% CI [0.63, 1.22]). Reported use of strong prescription pain medication was also similar between beta blocker users and other anti-hypertensive users (7.7% vs 8.2%; within-person effect, OR=1.39, 95% CI [0.75, 2.55]). We found no evidence that beta blockers confer a clinically meaningful reduction in knee pain severity, areas of joint pain, or analgesic use among participants with symptomatic knee OA.

Self-Reported Metal Allergy and Early Outcomes After Total Knee Arthroplasty.

The impact of self-reported metal allergy (SRMA) in total knee arthroplasty (TKA) remains controversial. In the absence of objective tests, SRMA is often used as a screening tool for implant selection. The objective of this study was to determine the effect of SRMA on early outcomes after TKA. Between 2010 and 2014, 168 patients with SRMA underwent TKA; 150 (89%) received nickel-free implants, and 18 (11%) received cobalt-chrome implants that contained nickel. Mean age was 67 years, and 95% were female. A cohort of 858 TKA patients (mean age, 68 years) without SRMA matched by sex served as the control group. Outcomes included Knee Society Score (function [KSS-F] and knee [KSS-K]), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, knee flexion, further surgery, and complications. No differences were seen in KSS-F and KSS-K between patients with and without SRMA. The mean WOMAC pain scores were 89.1 for patients with SRMA and 85.2 for patients without SRMA (P=.030). Stiffness and physical function scores were similar. Knee flexion was similar. No differences were found between nickel-free and cobalt-chrome SRMA groups. Patients with SRMA and those without demonstrated similar early functional outcomes. Patients with SRMA who received standard cobalt-chrome implants had no significant difference in functional outcomes compared with patients with nickel-free implants. Better identifiers of patients at risk for adverse events due to implant material are needed. [Orthopedics. 2019; 42(6):330-334.].

Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee

Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments. To assess 2 subcutaneous tanezumab dosing regimens for OA. A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions. Patients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232). Co-primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores. Among 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were -0.60 [-1.07 to -0.13; P = .01] for tanezumab, 2.5 mg, and -0.73 [-1.20 to -0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, -0.66 [-1.14 to -0.19; P = .007] for tanezumab, 2.5 mg, and -0.89 [-1.37 to -0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, -0.22 [-0.39 to -0.05; P = .01] for tanezumab, 2.5 mg, and -0.25 [-0.41 to -0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively. Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings. ClinicalTrials.gov Identifier: NCT02697773.