E. Mahler

Measurement properties of the Health Assessment Questionnaire Disability Index for generalized osteoarthritis

OBJECTIVE Generalized OA (GOA) is highly prevalent in OA. Individuals with GOA typically suffer from limitations of both upper and lower extremity function, yet we lack a validated instrument to assess their activity limitations. An appropriate instrument might be the HAQ Disability Index (HAQ-DI). Therefore the aim of this study was to evaluate the measurement properties of the HAQ-DI in GOA. METHODS Data were used from a randomized controlled trial comparing the effectiveness of two multidisciplinary treatment programmes for patients with GOA. One hundred and thirty-seven of 147 included patients completed a standardized set of questionnaires before and after treatment. Interpretability, validity, reliability and responsiveness of the HAQ-DI were assessed using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments checklist (COSMIN). RESULTS Floor and ceiling effects were present. The content validity was questionable since the HAQ-DI encompasses activities that are either not relevant or too easy to perform as judged by patients and experts. Construct validity was good since 90% of the hypotheses were confirmed. Factor analysis confirmed the unidimensionality of the HAQ-DI (root mean square error of approximation = 0.057, χ(2)/df ratio = 1.48). Cronbachs α was 0.90, confirming internal consistency and the ICC was 0.81, reflecting good reliability. The minimal important change was 0.25 and the smallest detectable change was 0.60. We could not establish the responsiveness of the HAQ-DI. CONCLUSION The HAQ-DI showed good construct validity, internal consistency and reliability, whereas its content validity and responsiveness were limited. We recommend updating the items of the HAQ-DI in future research focusing on functional limitations in GOA. TRIAL REGISTRATION Dutch Trial Register NTR2137, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2137.

Patient Acceptable Symptom State in Knee Osteoarthritis Patients Succeeds Across Different Patient-reported Outcome Measures Assessing Physical Function, But Fails Across Other Dimensions and Rheumatic Diseases

Objective. The aims of this study are (1) to establish the Patient Acceptable Symptom State (PASS) cutoff values of different patient-reported outcome measures (PROM) assessing physical function in patients with knee osteoarthritis (OA), and (2) to assess the influence of sex, age, duration of symptoms, and presence of depressive feelings on being in PASS. Methods. Patients fulfilling the clinical American College of Rheumatology knee OA criteria received standardized nonsurgical treatment and completed different questionnaires at baseline and 3 months assessing physical function: Knee Injury and Osteoarthritis Outcome Score, Lequesne Algofunctional Index, Lower Extremity Functional Scale, numerical rating scale, and the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index. PASS values were defined as the 75th percentile of the score of questionnaires for those patients who consider their state acceptable. Results. Of the 161 included patients, 62% were women with a mean age of 59 years (SD 9) and body mass index of 30 kg/m2 (SD 5). Standardized PASS values (95% CI) for different questionnaires for physical function varied between 48 (44–54) and 54 (50–56). Female patients and patients feeling depressed were found to have a lower probability to be in PASS for physical function, with OR (95% CI) varying from 0.45 (0.23–0.91) to 0.50 (0.26–0.97) and from 0.27 (0.14–0.55) to 0.38 (0.19–0.77), respectively. Conclusion. PASS cutoff values for physical function are robust across different PROM in patients with knee OA. Our results indicate that PASS values are not consistent across dimensions and rheumatic diseases, and that the use of a generic PASS value for patients with OA or even patients with other rheumatic diseases might not be justifiable.

Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis: a randomised, double-blinded, sham-controlled trial

Objectives Low-dose radiation therapy (LDRT) for benign disorders such as knee osteoarthritis (OA) is widely used in some parts of the world, despite absence of controlled studies. We evaluated the effect of LDRT on symptoms and inflammation in patients with knee OA. Methods In this randomised, double-blinded, sham-controlled clinical trial (RCT), we recruited patients with knee OA (clinical ACR criteria) in the Netherlands, aged ≥50 years, pain score ≥5/10 and non-responding to analgesics and exercise therapy. Patients were randomised 1:1 to receive LDRT (1 Gray per fraction) or sham intervention six times in 2 weeks, stratified by pain (<8 versus ≥8/10). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months postintervention. Secondary outcomes included pain, function and inflammatory signs assessed by ultrasound, MRI and serum inflammatory markers. Results We randomly assigned 55 patients: 27 (49%) to LDRT and 28 (51%) to sham. At 3 months postintervention, 12/27 patients (44%; 95%  CI 26% to 63%) in the LDRT vs 12/28 patients (43%; 95%  CI 25% to 61%) in the sham group responded; difference 2% (95% CI 25% to 28%), OR adjusted for the stratifying variable was 1.1 (95% CI 0.4 to 3.2). Also, for clinical and any of the inflammatory signs, no differences were observed. Conclusions We found no substantial beneficial effect on symptoms and inflammatory signs of LDRT in patients knee OA, compared with sham treatment. Therefore, based on this RCT and the absence of other high-quality evidence, we advise against the use of LDRT as treatment for knee OA. Trial registration number NTR4574.

How should worsening in osteoarthritis be defined? Development and initial validation of preliminary criteria for clinical worsening in knee and hip osteoarthritis

Objectives: There is a need to define and validate measures of clinical worsening in knee and hip osteoarthritis (OA). The objectives of this exploratory project were: (i) to characterize worsening criteria in knee and hip OA using psychometric methods; (ii) to estimate their sensitivity and specificity; and (iii) to validate and compare these criteria with worsening criteria previously described in the literature. Method: An Expert Group reached consensus on 10 sets of worsening criteria to be tested in observational data sets of patients with knee or hip OA who received multimodal conservative treatment. These sets included 219 patients (derivation cohort) and 296 patients (validation cohort). We estimated minimal clinically important worsening (MCIW) values for pain, function, stiffness, and patient global assessment, and tested candidate worsening criteria in the derivation cohort. Finally, using patient judgement, we examined the sensitivity and specificity of literature-based as well as candidate worsening criteria in the validation cohort. Results: Literature-based worsening criteria were found to have high specificity (range 60–92%) but low sensitivity (range 22–59%). Two out of 10 candidate worsening criteria constructed by the Expert Group showed an acceptable combination of sensitivity and specificity in the derivation cohort, which was confirmed in the validation cohort (ranging from 54% to 65% and 67% to 74%, respectively). Conclusions: This is the first study to describe symptomatic worsening criteria based on expert consensus after examining the performance of candidate criteria derived from the literature applied to data in an observational study. The newly proposed worsening criteria show an acceptable combination of sensitivity and specificity.

AB0753 Longitudinal Study on Clinical Worsening of Osteoarthritis in The Knee and Hip over 2 Years: Worsening after Standardized Non-Surgical Treatment for 3 Months Is A Strong Predictor for Worsening at 2 Years

Background Despite the high incidence of clinically established knee and hip osteoarthritis (OA), few data are available on risk factors for clinical worsening. Objectives The aims are 1) to estimate the proportion of symptomatic knee and hip OA patients showing worsening at 2 years, after 3 months standardized conservative treatment, 2) to estimate the additional value of clinical criteria at 3 months in prediction worsening at 2 years compared to baseline values only. Methods All 302 patients in this longitudinal study in secondary care (CONTROL-PRO: patients fulfilling clinical ACR criteria for knee or hip OA and not yet deemed eligible for arthroplasty), received conservative treatment (the first 3 months standardized) which comprised education, physical therapy, step up analgesics and advice on weight reduction if indicated. The Western Ontario and McMaster Universities of Osteoarthritis Index (WOMAC) was used to measure pain and physical functioning as well as a numeric rating scale measuring patient global assessment. Measurements were performed at baseline, 3 months and 2 years. Worsening at 2 years was operationalized as fulfilling recently validated clinical worsening criteria for knee and hip OA or total joint replacement (TJR) in the index joint. Logistic regression was used to estimate the additional value of the determinant fulfilling clinical worsening at 3 months as predictor for worsening at 2 years. Results Baseline characteristics were 66% female, a mean age of 55.0 (SD 9.8) years, and median BMI of 27.9 kg/m2 (IQR 25.3–32.9). Median duration of symptoms was 3.8 years (IQR 1.6–10.4), the majority addressed the knee joint (84.8%) as index joint and 211 patients (69.9%) had Kellgren and Lawrence scores ≥2. A total of 79 (27.8%) and 181 patients (59.9%) clinically worsened at 3 months and 2 years respectively. 75 Out of 181 patients (41.4%) who worsened at 2 years, had undergone a TJR in the index joint on average 1.1 years (SD 0.5) after inclusion. Of these 181 patients who worsened over time, a lower proportion of patients underwent a TJR of the knee than a TJR of the hip in their index joint (34.5% versus 72.7% respectively, p<0.0001). Patients who clinically worsened at 3 months showed an increased odds ratio of 5.8 to clinically worsen at 2 years as well (95% CI 2.2–15.6, p<0.001). Similar results were obtained when only TJR at 2 years as outcome measure was used. Conclusions A high proportion of knee and hip OA patients in secondary care who are not deemed yet eligible for surgery at inclusion, showed clinical worsening over 2 years, even after conservative treatment. At 2 years, we observed relatively less TJRs for knee OA than for hip OA. Our results show that clinical worsening at 3 months is a strong independent risk factor for worsening at 2 years. A short conservative treatment trial could thus be used in clinical practice to select patients in whom TJR should be considered. Disclosure of Interest None declared

AB0864 The Efficacy and Safety of Low-Dose Radiotherapy on Pain and Functioning in Patients with Osteoarthritis: A Systematic Review

Background Low dose Radiotherapy (LD-RT) is used for treating non-malignant diseases since its introduction in the late 19th century.1 Currently, osteoarthritis (OA) is a well-accepted indication for LD-RT in more than 80% of the radio-therapeutic centres in Eastern Europe.2 In Germany, over 9,000 patients with OA are treated with RT annually.3 LD-RT is considered safe, as the total dose that is used for these patients is relatively small; the effective dose is comparable to an abdominal CT-scan.4 Furthermore, the dose for treating OA is targeted on the affected joint, minimising the risk for exposure of other tissues. Multiple studies using animal models show that LD-RT reduces inflammation in OA.5 Despite high acceptance in large parts of the world and widespread use, the level of evidence on the effect of radiotherapy on pain and function in OA patients remains unclear. Objectives To systematically review literature findings on the effect of radiotherapy on pain and function in patients with osteoarthritis. Methods A computerised search with broad search terms was performed in the PubMed, EMBASE and Web of Science databases. Primary inclusion criteria were: osteoarthritis as indication for treatment, radiotherapy as intervention, written in English, German or Dutch and published since 1980. Literature overviews were excluded. Study quality was assessed using the EPHPP Quality Assessment Tool for Quantitative Studies (scale: strong, moderate, weak). Screening for eligibility and quality assessment was performed independently by MM and CvdE. Results were extracted by MM and are presented as reported in the original publication. Short-term (≤3months) and long term (>3months) results are presented separately. Results The literature search generated 6,124 citations. Seven studies were suitable for inclusion, all with retrospective observational design and without control group. The main results are shown in Table 1. The methodological quality of all studies was judged as weak. The age of included OA patients ranged from 30 to 90 years, the duration of their complaints ranged from <0.5 to 15 years. As intervention, most studies used 2-3 RT-sessions per week for two weeks, some with a pause of six weeks before this was repeated. Overall, a dose of 0.5-1.0 Gy per session was applied, with a total dose of 3.5-6.0 Gy. In general, non-validated single-item measurement instruments were used to evaluate the effect of RT on pain. Orthopaedic scores were used to assess functioning in three studies. One study reported on side effects, none occurred. Conclusions The included studies reported positive results of LD-RT on pain and functioning. Little is known about its side effects. The strength of evidence is very weak due to inferior study designs and outcome measures. Considering the widespread use of radiotherapy for OA and the effects reported in animal studies, a high quality RCT with well-defined outcome measures is warranted. References Sokoloff N, Wien Med Wschr (1898);12. Leer JW, Radiotherapy and Oncology (1998);48 249–257. Seegenschmiedt H, Strahlenther Onkol. (2004);180 718-30. Leer JW, Radiotherapy and Oncology (2007);83 175–177. Arenas M, Strahlenther Onkol (2012);188 975–981. Disclosure of Interest None declared

AB0851 Assessment and Comparison of Responsiveness of Four Patient Reported Outcome Measures to Assess Physical Function in Knee OA: Womac-PF Subscale Responds Best

Background Although physical function is one of the core outcome domains in knee OA, the ability of a measurement instrument to detect changes over time in the construct (physical function) being measured, i.e. the responsiveness, has never been tested as currently recommended by the Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN)1. Objectives The aim of the current study was to compare the responsiveness of four disease-specific patient related outcome measures (PROMs) of physical function for patients with knee osteoarthritis receiving conservative treatment. Methods Consecutive patients fulfilling the clinical ACR criteria for knee OA visiting our specialized knee OA outpatient clinic were invited to complete questionnaires at baseline and 3 month follow-up. Physical function was measured with four PROMs: the Lequesne Algofunctional index (LAI), Lower Extremity Functional Scale (LEFS), Knee Injury and Osteoarthritis Outcome Function Short Form (KOOS-PS) and Western Ontario and McMaster University Osteoarthritis Index Physical Function subscale (WOMAC-PF). Responsiveness was investigated by testing a priori defined hypotheses formulated by an expert group in analogy to construct validity1. These a priori defined hypotheses addressed expected correlations between changes in physical function with changes in other (un)related measures (pain, fatigue, self-efficacy, coping, anxiety, depression and mental health) or expected differences in correlation in changes between groups. The expert group reached consensus on 15 a priori defined hypotheses and responsiveness was considered positive if >75% of the hypotheses were confirmed. Results Of the 161 included patients, 61% was female with a mean age of 59.0 years (SD 9.3) and BMI of 29.7 kg/m2 (SD 5.0). The majority (n=129, 80.6%) remained stable and 14 patients (8.8%) indicated (very) much worsening in their physical function assessed by the transition question after 3 months. The 17 patients (10.6%) who indicated (very) much improvement, showed significant mean improvement in physical function after 3 months in all four disease-specific PROMs compared with baseline (p<0.05). We could confirm 12 out of 15 of the a priori defined hypotheses (80%) using the physical function subscale of the WOMAC. For the LAI, LEFS and KOOS-PS, respectively 10 (67%), 11 (73%) and 11 (73%) hypotheses were confirmed respectively. Conclusions This is the first study that comprehensively assessed and compared the responsiveness of physical function measured with LAI, LEFS, KOOS-PS and WOMAC-PF according to the latest standards1. Our results suggest that the WOMAC-PF is potentially better able to detect changes over time in physical function than the LAI, LEFS and KOOS-PS in a population of patients with knee OA receiving conservative treatment. We therefore recommend that clinicians and researchers should prefer the WOMAC-PF subscale in future clinical trials to evaluate the effectiveness of (conservative) treatment. References Mokkink LB, Terwee CB, Knol DL, Stratford PW, Alonso J, Patrick DL et al. The COSMIN checklist for evaluating the methodological quality of studies on measurement properties: a clarification of its content. BMC Med Res Methodol 2010; 10: 22 Disclosure of Interest None declared

SAT0594-HPR Measurement Properties of the Health Assessment Questionnaire Disability Index in Patients with Generalized Osteoarthritis (GOA)

Background Individuals with GOA typically suffer from limitations of both upper and lower extremity function. However, current OA specific instruments for activity limitations are usually site specific and do not involve activities of both upper and lower extremities. We hypothesized that the Health Assessment Questionnaire Disability Index (HAQ-DI), originally developed for patients with inflammatory arthritis, might be appropriate to measure functional limitations in GOA. Objectives To evaluate the measurement properties (content validity, construct validity and reliability) of the HAQ-DI in patients with GOA. Methods Data were used from a randomized clinical trial evaluating the effectiveness of a 6-week multidisciplinary treatment program for patients with GOA. 137 patients completed a standardized set of questionnaires before and directly after treatment. The measurement properties of the HAQ-DI were assessed according the Consensus Based Standards for the Selection of health Status Measurement Instruments Checklist1. Floor and ceiling effects for each HAQ-DI category at baseline were considered present if >15% of patients scored the worst or best possible score. For content validity, 17 health professionals were asked to judge the relevance of each HAQ-DI item. Construct validity was assessed by computing associations (Pearson r) between HAQ-DI scores and scores on other clinical (un)related measures. Reliability was assessed by confirmatory factor analysis (CFA), Cronbachs alpha and intra-class correlation coefficient (ICC). The minimal important change (MIC) score was calculated using an anchor based method. Results Of 137 patients (mean age 60 (SD 8) years; (85%) female), 93% reported to have complaints in both the upper and lower extremities. The mean (SD) HAQ-DI score was 1.27 (0.5) at baseline and 1.20 (0.5) at follow-up. 20% - 30% of patients reported the best possible score on the HAQ-DI categories eating, dressing and gripping; 16% reported the worst possible score on the category hygiene. The content validity was questionable since according to the health professionals the HAQ-DI encompasses 9 (out of 20) activities that are not relevant or too easy to perform for GOA patients. Construct validity was rated positive given the moderate to strong associations with related constructs and weak associations with unrelated constructs. The CFA confirmed the unidimensionality of the HAQ-DI (Root Mean Square Error of Approximation =0.057, χ2/df ratio =1.48). Cronbachs alpha was 0.90, confirming internal consistency and the ICC was 0.81, reflecting good reliability. The MIC was 0.25 points and the smallest detectable change was 0.60 indicating that important changes cannot be distinguished from measurement error in individuals. Conclusions The HAQ-DI showed good construct validity and reliability to measure functional limitations in GOA. Yet, the content validity was unsatisfactory and we cannot support the use of the HAQ-DI to monitor individuals with GOA in daily clinical practice. Considering the unsatisfactory content validity, we recommend to update the items of the HAQ-DI when using the HAQ-DI in future research focusing on functional limitations in GOA. The latter might also be relevant for other arthritic populations. References Mokkink et al. (2010). Qual Life Res 19:539-549. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3483

THU0208 Criteria for Clinical Important Worsening in Knee and Hip Osteoarthritis: A First Development and Validation Round

Background In osteoarthritis (OA) multiple sets of criteria are available to distinguish between patients who clinically improve and those who do not. However, in addition to knowing who will improve after treatment, knowing who will deteriorate could help patients and doctors to make informed treatment choices. In contrast to important improvement, important worsening in OA is not well defined. Objectives 1. To estimate the minimal clinically important worsening (MCIW) values for pain, function, stiffness and patient global assessment (PGA) in patients with knee and hip OA 2. To examine the sensitivity and specificity of several sets of previous described and proposed worsening criteria for determining worsening Methods Data were used from a cohort of knee and hip OA outpatients visiting our department who received standardised evidence-based tailored conservative treatment in a stepped-care format for 3 months. Sub cohort I comprised 250 patients (mean age 56 years, 67% female, 83% knee OA) with three-month follow up and sub cohort II consisted of 400 patients (mean age 56 years, 66% female, 88% knee OA) with two-year follow up. For this study baseline and three month data were used. First we estimated MCIW values for pain (numeric rating scale 0-10 (NRS) and WOMAC pain scale 0-100), WOMAC function (scale 0-100), WOMAC stiffness (scale 0-100) and PGA (scale 0-10) in cohort I using an anchor-based 7-point Likert transition scale. Second, on the basis of those MCIW values and on an inventory of definitions of worsening in the literature an expert group selected and defined different potential sets of worsening, varying in the number of outcome measures incorporated and the amount of change in relative and absolute MCIW values determined in the previous step. These sets included the inverse of the OMERACT-OARSI responder criteria, the inverse of the improvement criteria by Tubach, MCIW values of OA after rehabilitation (Angst) and several sets based on the inverse of these criteria with different relative and absolute changes. Third, in sub cohort ll we evaluated the sensitivity and specificity of the 5 MCIW values generated from sub cohort I and the different sets of worsening using the same anchor-based transition scale. Results The estimated MCIW values for absolute and relative (compared to baseline) worsening at 3 months were: NRS pain 1.7, 13%; WOMAC pain 2.7, 8%; WOMAC function 4.6, 2%; WOMAC stiffness 5.6, 25% and PGA 0.76, 14%. The sensitivity of previously used definitions for worsening and inverse of improvement criteria was low (range 17-40%) while specificity was good (range 70-92%). Using our estimated MCIW values, sensitivity above 50% was observed. Sensitivity of 60-70% was observed in sets proposed by the expert group in which less stringent criteria were used compared to improvement criteria. Conclusions Sensitivity of previously described definitions for worsening and criteria being the inverse of improvement criteria was low, while specificity was good. Our results suggest that, compared with improvement criteria, criteria for worsening should incorporate relatively small absolute and relative changes and that sensitivity is better in less stringent sets. References Pham et al. Osteoarthritis Cart 2004;12;389-99 Tubach et al. Arthritis Care & Research 2012;64;1699-1707 Angst et al. J Rheumatol 2002;29;131-138 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3499

SAT0324 The Association between the Proinflammatory Protein S100A8/A9 with Clinical Data and Structural Abnormalities in Patients with Established Knee, Hip and Hand Osteoarthritis

Background Serum levels of the heterodimer S100A8/A9 have shown to correlate well with disease activity and structural abnormalities in patients across several inflammatory rheumatic diseases and seems crucially involved in cartilage destruction in osteoarthritis (OA) in murine models. Earlier we found that S100 serum levels correlate with development of human OA. However, whether there is an association between S100A8/A9 levels and clinical and structural data in patients with established OA is unknown. Objectives To explore the association between the proinflammatory protein S100A8/A9 serum level with clinical data and structural abnormalities in patients with established knee, hip or hand OA. Methods A cross sectional exploratory study was conducted with 162 patients fulfilling the ACR clinical criteria for knee (n=57), hip (n=47) or hand OA (n=58). Clinical data consisted of pain, stiffness, function, ESR and C-reactive protein serum levels. Pain, stiffness and function subscales were calculated and normalized using the WOMAC questionnaires for knee and hip OA and AUSCAN index for hand OA. Outcome measures for structural abnormalities included the K&Lscore (for hand OA mean score), sum score of osteophytes and joint space narrowing grades using the OARSI atlas. In case of non-normal distribution, outcome measures were dichotomized using the median split method. The association between serum levels of S100A8/A9 (independent) and clinical data (dependent) or structural abnormalities (dependent) was analyzed using linear regression or logistic regression when appropriate. For multivariate analyses, α < 0.10 was set. Results The mean age was 56 years, 71% was female and 61% had K&L score ≥ 2. In the hand OA group, the mean age was higher and more women were included. Furthermore, hand OA patients reported the longest duration of symptoms, least pain and had the highest normalized sum score of osteophytes. The knee patients reported the highest pain score and had the least sum score of osteophytes. The serum S100A8/A9 level did not differ between knee, hip and hand OA patients. For all joints together, serum S100A8/A9 level was negatively associated with the normalized sum score of osteophytes after adjustment for sex and BMI (adjusted OR 0.99 (95% CI 0.97-1.00, p=0.06) and positively associated with ESR (adjusted OR 1.002 (95%CI 1.000-1.004 p<0.05) for each increase of S100A8/A9 with 1 ng/ml. For hand OA patients, a negative association of S100A8/A9 with sum score of joint space narrowing was found (adjusted OR 0.993 (95%CI 0.984–1.001) p < 0.10). Conclusions Results from this cross sectional exploratory study do not support a role for serum S100A8/A9 levels as biomarker for clinical (normalized pain, stiffness and function) and structural outcome in established knee, hip and hand OA patients. The inverse relation with the sum score of osteophytes and joint space narrowing and the positive association with ESR underlines the previous finding that S100A8/A9 may reflect inflammatory synovial processes in patients with OA before structural abnormalities occur and warrant further exploration in longitudinal studies. Disclosure of Interest None Declared