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Knee osteoarthritis improvement and related biomarker profiles are sustained at 24 months following bariatric surgery
Abstracts / Osteoarthritis and Cartilage 25 (2017) S8eS75
fractures (SIF), osteonecrosis (ON) and rapidly progressive osteoarthritis (RPOA). The primary efficacy variable, change from baseline to week 16 in the WOMAC pain subscale score, was analyzed using a mixed-effect model repeated measure (MMRM) approach. Results: 419 subjects received at least one dose of study medication. At week 16, LS mean changes from baseline in the WOMAC pain subscale in patients were -2.25 for placebo and -3.03 to -3.65 for the fasinumab groups; all fasinumab groups showed significant improvement vs placebo (p¼<0.05). Improvements were also observed for WOMAC physical function and PGA. Symptoms scores returned toward baseline after treatment was discontinued. Over the entire 36-week treatment and follow-up period, fasinumab was generally well tolerated. As previously reported for the class of NGF antibodies, certain neuromuscular events, including arthralgia, paraesthesia, hypoaesthesia, and peripheral edema, occurred more commonly in fasinumab treated patients compared to the placebo-treated group. Over the 36-week period, the incidence of adjudicated arthropathies was found to be dose-related, with a higher rate of patients experiencing arthropathies in the higher dose groups [12 percent (9mg), 7 percent (6mg), 5 percent (3mg), 2 percent (1mg) and 1 percent (placebo)]. Conclusions: In this 36-week clinical trial, fasinumab provided significant improvement compared to placebo in both pain and function in patients with moderate to severe OA. All doses provided efficacy, with the 9 mg dose providing the best effect. Fasinumab was generally well tolerated, with an apparent dose relationship for some adverse events, including adjudicated arthropathies. The efficacy and safety of lower doses of fasinumab, shown here, provide the basis for selection of the optimal treatment regimen for OA pain.
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surgery and was maintained through 24 months post-surgery (Fig. 1). This held true in the sleeve and bypass subgroups (with altered anatomy), while banding showed a less consistent DKOOS despite a similar trend in %EWL. By 24 months post-surgery, sleeve and bypass patients achieved a higher percent of their potential DKOOS pain improvement from pre-op than did banding (65.2% and 60.1% vs. 16.8% of remaining KOOS points to 100), and a higher percent of patients improved to any degree (93.1% and 88.9%, respectively, vs. 66.7%). Radiographic severity did not predict DKOOS at 12 or 24 months post-surgery. Levels of inflammatory adipokines and cytokines related to obesity and osteoarthritis, including leptin, IL-1Ra, IL-6, LPS, decreased over the course of the first year after bariatric surgery (previously shown) and these changes were sustained through 24 months post-surgery. This was specifically the case for leptin, whose most significant drop at one month post-surgery and subsequent stabilization corresponded closely with the initial reduction and stabilization in knee OA pain. Conclusions: Knee pain relief from bariatric weight loss surgery, previously reported at the 12-month mark, was largely maintained at 24 months. Most knee pain relief occurs during the first month postbariatric surgery, before much of the weight loss, suggesting that there might be a metabolic impact beyond mechanical load reduction on joints. Leptin may be a key biomarker that contributes to knee pain relief as its serum concentration closely mirrored pain relief post-surgery.
74 KNEE OSTEOARTHRITIS IMPROVEMENT AND RELATED BIOMARKER PROFILES ARE SUSTAINED AT 24 MONTHS FOLLOWING BARIATRIC SURGERY S.X. Chen y, F. Bomfim y, T. Mukherjee y, E. Wilder y, S. Aharon y, K. Toth y, L. Browne y, R. La Rocca Vieira y, J. Patel y, C. Ren-Fielding y, M. Parikh y, S.B. Abramson y, M. Attur y, J. Samuels z. y NYU Langone Med. Ctr., New York, NY, USA; z NYU Langone Hosp. for Joint Diseases, New York, NY, USA Purpose: Patients who are obese and have knee osteoarthritis (OA) face barriers to successfully relieve their symptoms, as diet, exercise, and physical therapy to relieve weight loss or knee pain improvement fail. Thus, recent studies have turned to bariatric surgery as a method for reducing the mechanical load on joints and relieve pain. While it is intuitive that bariatric weight loss improves knee pain, it is not clear how much is due to decreased mechanical load or metabolic changes. The goal of this study is to quantify the degree and duration of improvement in knee OA pain and symptoms following bariatric weight loss, identify and track the biomarkers related to knee OA and obesity, and compare knee pain and symptom improvement between different bariatric surgical methods (gastric bypass, sleeve gastrectomy, and laparoscopic adjustable gastric banding). Methods: Patients from Bellevue Hospital and NYU Langone Medical Center were screened for knee pain prior to bariatric surgery. We required pain for 15 days/month and VAS pain 30, excluding patients with lupus, inflammatory arthritis, crystal disease, psoriasis, and/or bilateral knee replacement. Enrolled patients took standing knee x-rays for Kellgren-Lawrence (KL) grading. We measured BMI and used the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire at baseline and 1, 3, 6, 12, and 24 months post-surgery, calculating percent excess weight loss (%EWL) and DKOOS. We collected blood at baseline and follow-ups to study biomarkers for predicting KOOS scores. Results: Of 536 patients considering bariatric surgery, we found 308 with knee pain and enrolled 176 (91.5% female; BMI 43.6±7 kg/m2, 32e61; age 42±11 years, 18e73) well distributed in x-ray severity (KL 0e4). A total of 150 patients had surgery, with 35 undergoing bypass surgery, 97 undergoing sleeve gastrectomy, and 18 undergoing laparoscopic gastric banding. Across all surgery types, we found a modest but statistically significant correlation between %EWL and DKOOS pain at one year following surgery (R ¼ 0.262, n ¼ 114, p ¼ 0.005), similar to other time intervals and to other KOOS measures, but with some attenuation and loss of significance by 24 months (R ¼ 0.181, n ¼ 91, p ¼ 0.096). While patients lost weight consistently through the first year and generally sustained their new BMI by the 24-month mark, their mean knee improvement plateaued after only one month after
75 KNEE OSTEOARTHRITIS PHENOTYPES AND THEIR RELEVANCE FOR OUTCOMES: A SYSTEMATIC REVIEW OF THE LITERATURE L.A. Deveza y, L. Melo y, T. Yamato z, K. Mills x, D.J. Hunter y. y Rheumatology Dept., Royal North Shore Hosp. and Inst. of Bone and Joint Res., Kolling Inst., Univ. of Sydney, Sydney, Australia; z The George Inst. for Global Heath, Univ. of Sydney, Sydney, Australia; x Faculty of Med. and Hlth.Sci., Dept. of Hlth.Professions, Macquarie Univ., Sydney, Australia Purpose: Knee osteoarthritis (OA) has been increasingly recognized as a heterogeneous condition, with a variety of mechanisms leading to joint destruction and multiple factors involved in the perception of pain. At present, however, there is a lack of clarity over the phenotypes that may comprise the disease OA. The main purpose of this systematic review was to examine the disease characteristics used to identify distinct knee OA phenotypes and the relation of the different phenotypes identified with outcomes. Methods: Our search was performed in Medline via Ovid, EMBASE, Web of Sciences, CINAHL, and Scopus (Health Sciences) databases from inception to September 2016. Included studies were: human studies of individuals with symptomatic knee OA that aimed to identify subgroups of knee OA based on any type of OA characteristic (e.g. structural, clinical, laboratory, trajectory of disease, etc.). Any type of subgrouping analytical strategy was permitted. Inclusion was limited to observational studies that attempted to determine the clinical relevance of the phenotypes by assessing their association with clinical or structural imaging outcomes. Two reviewers independently screened abstracts and full-texts for inclusion and assessed studies' methodological quality
fractures (SIF), osteonecrosis (ON) and rapidly progressive osteoarthritis (RPOA). The primary efficacy variable, change from baseline to week 16 in the WOMAC pain subscale score, was analyzed using a mixed-effect model repeated measure (MMRM) approach. Results: 419 subjects received at least one dose of study medication. At week 16, LS mean changes from baseline in the WOMAC pain subscale in patients were -2.25 for placebo and -3.03 to -3.65 for the fasinumab groups; all fasinumab groups showed significant improvement vs placebo (p¼<0.05). Improvements were also observed for WOMAC physical function and PGA. Symptoms scores returned toward baseline after treatment was discontinued. Over the entire 36-week treatment and follow-up period, fasinumab was generally well tolerated. As previously reported for the class of NGF antibodies, certain neuromuscular events, including arthralgia, paraesthesia, hypoaesthesia, and peripheral edema, occurred more commonly in fasinumab treated patients compared to the placebo-treated group. Over the 36-week period, the incidence of adjudicated arthropathies was found to be dose-related, with a higher rate of patients experiencing arthropathies in the higher dose groups [12 percent (9mg), 7 percent (6mg), 5 percent (3mg), 2 percent (1mg) and 1 percent (placebo)]. Conclusions: In this 36-week clinical trial, fasinumab provided significant improvement compared to placebo in both pain and function in patients with moderate to severe OA. All doses provided efficacy, with the 9 mg dose providing the best effect. Fasinumab was generally well tolerated, with an apparent dose relationship for some adverse events, including adjudicated arthropathies. The efficacy and safety of lower doses of fasinumab, shown here, provide the basis for selection of the optimal treatment regimen for OA pain.
S57
surgery and was maintained through 24 months post-surgery (Fig. 1). This held true in the sleeve and bypass subgroups (with altered anatomy), while banding showed a less consistent DKOOS despite a similar trend in %EWL. By 24 months post-surgery, sleeve and bypass patients achieved a higher percent of their potential DKOOS pain improvement from pre-op than did banding (65.2% and 60.1% vs. 16.8% of remaining KOOS points to 100), and a higher percent of patients improved to any degree (93.1% and 88.9%, respectively, vs. 66.7%). Radiographic severity did not predict DKOOS at 12 or 24 months post-surgery. Levels of inflammatory adipokines and cytokines related to obesity and osteoarthritis, including leptin, IL-1Ra, IL-6, LPS, decreased over the course of the first year after bariatric surgery (previously shown) and these changes were sustained through 24 months post-surgery. This was specifically the case for leptin, whose most significant drop at one month post-surgery and subsequent stabilization corresponded closely with the initial reduction and stabilization in knee OA pain. Conclusions: Knee pain relief from bariatric weight loss surgery, previously reported at the 12-month mark, was largely maintained at 24 months. Most knee pain relief occurs during the first month postbariatric surgery, before much of the weight loss, suggesting that there might be a metabolic impact beyond mechanical load reduction on joints. Leptin may be a key biomarker that contributes to knee pain relief as its serum concentration closely mirrored pain relief post-surgery.
74 KNEE OSTEOARTHRITIS IMPROVEMENT AND RELATED BIOMARKER PROFILES ARE SUSTAINED AT 24 MONTHS FOLLOWING BARIATRIC SURGERY S.X. Chen y, F. Bomfim y, T. Mukherjee y, E. Wilder y, S. Aharon y, K. Toth y, L. Browne y, R. La Rocca Vieira y, J. Patel y, C. Ren-Fielding y, M. Parikh y, S.B. Abramson y, M. Attur y, J. Samuels z. y NYU Langone Med. Ctr., New York, NY, USA; z NYU Langone Hosp. for Joint Diseases, New York, NY, USA Purpose: Patients who are obese and have knee osteoarthritis (OA) face barriers to successfully relieve their symptoms, as diet, exercise, and physical therapy to relieve weight loss or knee pain improvement fail. Thus, recent studies have turned to bariatric surgery as a method for reducing the mechanical load on joints and relieve pain. While it is intuitive that bariatric weight loss improves knee pain, it is not clear how much is due to decreased mechanical load or metabolic changes. The goal of this study is to quantify the degree and duration of improvement in knee OA pain and symptoms following bariatric weight loss, identify and track the biomarkers related to knee OA and obesity, and compare knee pain and symptom improvement between different bariatric surgical methods (gastric bypass, sleeve gastrectomy, and laparoscopic adjustable gastric banding). Methods: Patients from Bellevue Hospital and NYU Langone Medical Center were screened for knee pain prior to bariatric surgery. We required pain for 15 days/month and VAS pain 30, excluding patients with lupus, inflammatory arthritis, crystal disease, psoriasis, and/or bilateral knee replacement. Enrolled patients took standing knee x-rays for Kellgren-Lawrence (KL) grading. We measured BMI and used the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire at baseline and 1, 3, 6, 12, and 24 months post-surgery, calculating percent excess weight loss (%EWL) and DKOOS. We collected blood at baseline and follow-ups to study biomarkers for predicting KOOS scores. Results: Of 536 patients considering bariatric surgery, we found 308 with knee pain and enrolled 176 (91.5% female; BMI 43.6±7 kg/m2, 32e61; age 42±11 years, 18e73) well distributed in x-ray severity (KL 0e4). A total of 150 patients had surgery, with 35 undergoing bypass surgery, 97 undergoing sleeve gastrectomy, and 18 undergoing laparoscopic gastric banding. Across all surgery types, we found a modest but statistically significant correlation between %EWL and DKOOS pain at one year following surgery (R ¼ 0.262, n ¼ 114, p ¼ 0.005), similar to other time intervals and to other KOOS measures, but with some attenuation and loss of significance by 24 months (R ¼ 0.181, n ¼ 91, p ¼ 0.096). While patients lost weight consistently through the first year and generally sustained their new BMI by the 24-month mark, their mean knee improvement plateaued after only one month after
75 KNEE OSTEOARTHRITIS PHENOTYPES AND THEIR RELEVANCE FOR OUTCOMES: A SYSTEMATIC REVIEW OF THE LITERATURE L.A. Deveza y, L. Melo y, T. Yamato z, K. Mills x, D.J. Hunter y. y Rheumatology Dept., Royal North Shore Hosp. and Inst. of Bone and Joint Res., Kolling Inst., Univ. of Sydney, Sydney, Australia; z The George Inst. for Global Heath, Univ. of Sydney, Sydney, Australia; x Faculty of Med. and Hlth.Sci., Dept. of Hlth.Professions, Macquarie Univ., Sydney, Australia Purpose: Knee osteoarthritis (OA) has been increasingly recognized as a heterogeneous condition, with a variety of mechanisms leading to joint destruction and multiple factors involved in the perception of pain. At present, however, there is a lack of clarity over the phenotypes that may comprise the disease OA. The main purpose of this systematic review was to examine the disease characteristics used to identify distinct knee OA phenotypes and the relation of the different phenotypes identified with outcomes. Methods: Our search was performed in Medline via Ovid, EMBASE, Web of Sciences, CINAHL, and Scopus (Health Sciences) databases from inception to September 2016. Included studies were: human studies of individuals with symptomatic knee OA that aimed to identify subgroups of knee OA based on any type of OA characteristic (e.g. structural, clinical, laboratory, trajectory of disease, etc.). Any type of subgrouping analytical strategy was permitted. Inclusion was limited to observational studies that attempted to determine the clinical relevance of the phenotypes by assessing their association with clinical or structural imaging outcomes. Two reviewers independently screened abstracts and full-texts for inclusion and assessed studies' methodological quality