Targeted Therapies in RA: Real World Comparative Effectiveness Research

The objective of this study was to compare the effectiveness of abatacept to anti-TNFs using the following: Change in disease activity based on the Clinical Disease Activity Index, and (CDAI) Achievement of remission based on the CDAI. Among this small sample of RA patients in a real-world setting, treatment with abatacept was not associated with any differences in response or remission rates from those seen with anti-TNFs based on mean change in CDAI and achievement of CDAI remission. This study suggests similar effectiveness of abatacept and anti-TNFs in biologic naïve RA patients. Further research with a larger sample size is needed to confirm these findings

Social Support and Total Joint Replacement: Differences Preoperatively between Patients Living Alone and Those Living with Others

Introduction: Social relationships affect mental health, physical health, and mortality risk. Little is known about social support and patients electing to have total joint replacement (TJR) surgery. We explored the differences between participants living alone and those living with at least one other adult prior to TJR surgery. Materials & methods: Preoperative and 6 month postoperative FORCE-TJR Registry survey data were collected from 6269 primary unilateral TJR patients between May 2011 and December 2013. Data included demographics, comorbid conditions, operative joint pain severity (HOOS/KOOS), musculoskeletal disease burden, physical function (SF-36 PCS), and mental health (SF36 MCS). Results: Participants living alone were more likely to be older, female, on Medicare, with a high school education or less, and a racial/ethnic minority. Prior to surgery, they reported a greater number of comorbid conditions and non-surgical joints causing pain. Those living alone also had lower mean MCS summary measure, lower Social Functioning Scale score and a lower HOOS/KOOS Activities of Daily Living score before TJR. There were no differences preoperatively in mean BMI, mean PCS, or HOOS/KOOS surgical joint pain, symptoms, or quality of life scores between the two groups. Six months postoperatively, those living alone had lower mean PCS and MCS, but were more likely to report less pain and symptoms in the surgical joint. Unadjusted analyses of mean change over time found less improvement in PCS for those living alone compared to those not living alone. Conclusion: Recognizing differences in social support prior to TJR surgery could inform interventions and potentially influence patient reported outcomes postoperatively

Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid Arthritis

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA. METHODS: TCZ-naive patients from the Corrona RA registry with prior exposure to \u3e /= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI \u3c /= 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose ( \u3c /= 10 mg; \u3e 10 to \u3c /= 15 mg; \u3e 15 to \u3c /= 20 mg; \u3e 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups. CONCLUSIONS: In this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC. Plain language summary available for this article

6-Month Change in Pain and Function by Pre-Operative Pain and Function among Patients Selected for Total Knee Replacement in the United States

Background/Purpose: The increase in total knee replacements (TKRs) between 1979 and 2006 is staggering. Debate is growing regarding the appropriate utilization of TKRs. We examined pain, function, quality of life (QOL), and satisfaction at 6-month post-surgery by pain and function at time of surgery. Methods: Data came from the nationally representative FORCE-TJR cohort of patients from 150 surgeons. Participants had primary, unilateral TKRs due to osteoarthritis between 2011 and 2014. Their knee pain (KOOS), physical functions (SF36), and QOL were measured at pre- and 6 months post-surgery. We classified patients as having high or low pre-operative pain (KOOS Pain \u3c 70 vs. ≥70), low or high pre-operative physical function (SF-36 PCS \u3c 40 vs. ≥40), and grouped as: 1) Low pain-High function (LP-HF), 2) Low pain-Low function (LP-LF), 3) High pain-High function (HP-HF), and 4) High pain-Low function (HP-LF). We compared pre- and post-operative changes in pain and function scores among the four groups. Results: Of 4,563 participants, 5% had pre-operative LP-HF and 75% HP-LF. By 6-month post-surgery, 85% of LP-HF patients reported no change and 4% reported worse symptoms; the HP-LF group had 18% no change and 52% with large improvement. For function in the LP-HF group, mean 6-month change (SD) was 2.6 (7.8), with post-operative mean of 50.0 (7.4). Mean change for the HP-LF group was 11.9 (9.0), with post-operative mean of 42.0 (9.5). For pain score in the LP-HF group, mean 6-month change was 8.3 (14.6), with post-operative mean (SD) of 88.9 (13.0). The HP-LF group had average improvement of 37.2 (19.7), and post-operative mean of 79.9 (17.3). QOL was better among the LP-HF than HP-LF groups; satisfaction was similar. Conclusion: The majority of patients had appropriate TKR utilization and achieved large improvement in pain and function. Patients with pre-operative LP-HF achieved the smaller mean change, but better absolute outcomes

Clinical Profile and Disability Levels of Younger vs. Older TKR and THR Patients in a National Research Consortium

Introduction: A growing number of patients under 65 years old undergo total knee replacement (TKR) and total hip replacement (THR).1 This trend has raised concerns that younger patients may receive surgery prematurely. We examined demographic and clinical factors in younger versus older patients in a national sample of THR and THR patients. Methods: Patients undergoing primary TKR and THR from 7/1/11 through 12/03/12 were identified from a national research consortium that gathers demographics, comorbid conditions (Charlson Comorbidity Index), Short Form 36 Physical Component Score (PCS) and Mental Component Score (MCS), burden of musculoskeletal disease using the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip injury and Osteoarthritis Outcome Score (HOOS) and the Oswestry Low Back Pain Disability Questionnaire. Descriptive statistics were performed. Results: TKR patients included 1326 younger ( Conclusion: Younger patients have fewer medical illnesses at the time of TKR or THR, but have greater functional impairment and higher rates of obesity and smoking as well as lower mental health scores

Differences in Patient Characteristics Prior to TKA and THA Between Switzerland and the US

Introduction: Total knee (TKA) and hip (THA) arthroplasty results, including patient-reported outcome measures (PROMs), complication and implant survival rates, are often generalized across countries, although patient- and environment-dependent factors may differ considerably. We described and compared preoperative characteristics from two large TKA and THA cohort studies, one in Switzerland and the other in the US. Materials & methods: Patient characteristics were collected prospectively on all elective primary TKAs and THAs performed (1) at a large tertiary center in Switzerland between 1/2010 and 12/2011 and (2) in FORCE-TJR, a US diverse, large national sample between 6/2011 and 8/2012. Information was obtained on age, sex, BMI, diagnosis, medical co-morbidities, and PROMs (WOMAC pain and function, SF-12/36 physical and mental component scores). We calculated risk ratios, and mean differences, and effect sizes, to compare preoperative scores. Results: Overall, 2508 TKAs and 1,912 THAs (US) and 855 TKAs and 673 THAs (Swiss) were evaluated. U.S. patients, compared to Swiss, were younger (mean age TKA: 67 vs. 72 yrs; THA: 64 vs. 68 yrs), more obese (BMI ≥35 TKA: 27% vs. 17%; THA: 39% vs. 23%). US TKA patients had more cardiac disease, higher preoperative WOMAC pain scores (52 vs. 41 points) indicating less knee-specific pain at time of TKA. US THA patients had more diabetes (13% vs. 10%), higher WOMAC pain scores (47 vs. 40 points) indicating less hip-specific pain at the time of THA. While significant physical disability (SF) was reported in both countries, US TKA and THA patients reported lower physical function scores. Conclusion: We found substantial differences in baseline characteristics with younger age, greater obesity, in the US TKA and THA patients, and more cardiac disease (TKA), diabetes and preoperative hip pain (THA). Significant levels of disability were reported across countries. These findings call for adequate risk adjustment in cross-cultural comparisons

Do Younger TKR and THR Patients Have Similar Disability at Time of Surgery as Older Adults? Lessons from FORCE-TJR

Introduction: The number of US patients under 65 year old who are undergoing total knee replacement (TKR) and total hip replacement (THR) has been rising, raising concerns that younger patients may receive surgery prematurely. Therefore, we examined demographics and clinical factors and compared the severity of operative knee pain and functional status in younger versus older TKR patients from a US national sample. Materials & methods: The FORCE-TJR registry gathers data from patients, surgeons and hospitals on sociodemographic factors (age, sex, race), BMI, comorbid conditions using the modified Charlson comorbidity scores, burden of musculoskeletal disease using the Knee/Hip injury and Osteoarthritis Outcome Score (KOOS/HOOS) in both knees and hips, emotional health based on the Short Form 36 (SF-36) Mental Component Score (MCS) and physical function based on the Physical Component Score (SF-36 PCS). Results: We analysed data from 2035 younger (\u3c65) and 3084 older (≥65) TKR patients and 1780 younger and 1831 older THR patients. Younger TKR and THR patients were more likely nonwhite (TKR: 13.1% vs. 6.6%; THR: 51.7% vs. 48.3%),), with greater body mass index (mean BMI TKR: 33.1 vs. 30.5; THR: 29.9 vs. 28.4), smokers, had fewer number of comorbid conditions. Younger TKR patients reported lower emotional health (MCS 49.1 vs. 52.6), greater joint pain, stiffness and functional impairment (based on estimated WOMAC) and global functional impairment (using PCS). Younger THR patients reported greater joint pain, stiffness and functional impairment (estimated WOMAC) but not global function. Conclusion: At the time of TKR and THR, younger patients have fewer medical illnesses, but higher rates of obesity and smoking as well as lower mental health scores. Younger have the same or greater joint specific and global functional impairment compared to older patients, suggesting surgeons use comparable standards for selecting TKR and THR candidates in younger and older adults

Gout Knowledge, Beliefs and Treatment Practices in a National Sample of US Primary Care Providers

Objectives: We sought to examine primary care providers’ gout knowledge and reported treatment patterns in comparison to current treatment recommendations. Methods: We conducted a national survey of a random sample of primary care physicians (internists and family practitioners) to assess their treatment of acute, intercritical, and tophaceous gout in comparison to published European and American gout treatment recommendations and guidelines. Results: There were 838 respondents (response rate of 41%) most of whom worked in private practice (63%) with \u3e16 years experience (52%). For acute podagra, 16% reported care consistent with the recommendations including avoidance of anti-inflammatory drugs in the setting of renal insufficiency, use of colchicine at a dose of ≤ 1.8mg a day, and no initiation of a urate-lowering drug (ULD) during an acute attack (internists 21% vs. family practitioners 11%, p Conclusion: While internists were more likely than family practitioners to suggest recommended care, the majority of physicians did not report optimal treatment practices, suggesting further education is needed

Level of Pain and Disability at Time of TKR across the Past 10 Years: Results from Two National Cohorts

Introduction: A recent analysis reported a growing numbers of younger US adults with knee pain consistent with osteoarthritis (OA), although parallel analyses of knee x-rays found no increase in the classic radiographic signs of OA. The accompanying editorial evoked the need to understand if surgeons are performing surgery at an earlier stage in the condition.1 We compared pre-operative demographic and symptom profiles of a national US cohort of OA patients undergoing primary total knee replacement (TKR) in 2011-2012 with a national US cohort of patients from 2000-2004 to evaluate change, if any, in the timing of surgery as measured by patient pain and function. Methods: Following informed consent, the 2011-2012 national research study collected comprehensive data including demographic, comorbidity, and patient-reported pain and physical function, from a national sample of TKR patients. Comparable data from a national sample collected by one implant manufacturer between 2000-2004 were analyzed. Descriptive statistics compared the demographic and symptom profiles of the two cohorts. Results: There were fewer females in the 2011-2012 cohort (n=2363) compared to the 2000-2004 cohort (n=7144) (61.62%, vs. 66.72%). The 2011-2012 cohort was younger than the 2000-2004 cohort (66.7 years, vs. 68.12 years) and had a lower mean BMI (31.5 vs 32.3). Pre-operative physical function scores (SF36/PCS) were 3 points higher in 2011-2012 than 2000-2004 (33.2 vs. 30.41). When compared to the national PCS norm of 50 (SD=10), TKR patients from both time periods reported pre-operative function levels almost 2 standard deviations below the national norm. There was no significant difference in terms of emotional health (SF36/MCS scores: 51.85 for the 2011-2012 cohort vs. 51.83 for the 2000-2004 cohort). Conclusion: Despite the significant growth in the use of primary TKR in the last decade, especially among younger patients, TKR patients continue to report significant disability at the time of surgery

What Outcomes are Important for Gout Patients? In-Depth Qualitative Research into the Gout Patient Experience to Determine Optimal Endpoints for Evaluating Therapeutic Interventions

BACKGROUND AND OBJECTIVES: Characterized by sudden onset of severe joint pain, swelling, redness, and tenderness to touch, gout \u27flare ups\u27 have a substantial impact on quality of life (QoL). This research employed a patient-centered approach to explore the symptoms and impacts of gout, and assess the content validity of existing patient-reported outcomes (PROs). METHODS: Qualitative interviews were conducted with 30 US gout patients (non-tophaceous: n = 20, tophaceous: n = 10) and five expert rheumatologists. Each interview included both concept elicitation (CE) questioning to learn about the patient experience and cognitive debriefing to assess the content validity of three PRO instruments (HAQ-DI, GAQ, and TIQ-20). Nine of the patients provided further real-time qualitative data through a smart phone application. All qualitative data were subject to thematic analysis using Atlas.ti. Two patient advisors and three expert clinicians were engaged as advisors at key stages throughout the research. RESULTS: Interview and real-time data identified the same core symptoms and proximal impact concepts. Severe pain (typically in joints of extremities) was described as the cardinal symptom, often accompanied by swelling, redness, heat, sensitivity to touch, and stiffness. Domains of QoL impacted included physical functioning, sleep, daily activities, and work. The PRO instruments were generally well-understood by patients, but each included items with questionable relevance to at least some of the sample, dependent on the specific joints affected. CONCLUSIONS: Gout patients experience severe pain in affected joints, resulting in substantial limitations in physical functioning. Both the HAQ-DI and the TIQ-20 are useful for specific research purposes in the gout population, although modifications are recommended