Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.

INTRODUCTION: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. METHODS: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. RESULTS: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. CONCLUSION: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.

Construct validity of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) treatment target cut-offs in a BASDAI treat-to-target axial spondyloarthritis cohort: a cross-sectional study.

OBJECTIVE: In axial spondyloarthritis (axSpA), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) are recommended for use in treat-to-target (T2T) strategies. However, BASDAI disease states may be a less suitable T2T instrument than ASDAS, since BASDAI contains non-disease activity related items. The objective of our study was to investigate the construct validity of BASDAI and ASDAS disease states. METHOD: We performed a single-centre cross-sectional study on BASDAI and ASDAS construct validity in long-term BASDAI T2T-treated axSpA patients. Our hypothesis was that BASDAI is less representative of disease activity than ASDAS owing to the focus on pain and fatigue, and missing an objective item, e.g. C-reactive protein (CRP). This was operationalized using several subhypotheses. RESULTS: The study included 242 axSpA patients. BASDAI and ASDAS disease states showed a similar relation to Patient Acceptable Symptom State and T2T protocol adherence. The proportions of patients with high BASDAI and ASDAS disease activity fulfilling Central Sensitization Inventory and fibromyalgia syndrome criteria were similar. The correlation with fatigue was moderate for both BASDAI (Spearman's rho 0.64) and ASDAS (Spearman's rho 0.54) disease states. A high ASDAS was strongly correlated with increased CRP (relative risk 6.02, 95% CI 3.0-12.09), while this correlation was not seen for BASDAI (relative risk 1.13, 95% CI 0.74-1.74). CONCLUSION: Our study showed moderate and comparable construct validity for BASDAI- and ASDAS-based disease activity states, with the expected exception of association with CRP. Therefore, no strong preference can be given for either measure, although the ASDAS seems marginally more valid.

Construct validity of the PROMIS PF-10 in patients with inflammatory rheumatic diseases and severe limitations in physical functioning.

OBJECTIVE: Assessing the construct validity of the Patient-Reported Outcomes Measurement Information System Physical Function 10-Item Short Form (PROMIS PF-10) in a subpopulation of rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) patients with severe limitations in physical functioning (PF). METHOD: RA/axSpA patients with severe functional limitations completed the PROMIS PF-10, Health Assessment Questionnaire - Disability Index (HAQ-DI for RA) or Bath Ankylosing Spondylitis Functional Index (BASFI for axSpA), 36-item Short Form Health Survey (SF-36), EuroQol 5-dimensions 5-level (index score, EQ-VAS), and performed the Six-Minute Walk Test (6MWT). Construct validity was assessed by computing Spearman rank or Pearson correlation coefficients and testing hypotheses about correlations between the PROMIS PF-10 and measures of PF and quality of life. RESULTS: Data from 316 patients (180 RA/136 axSpA, 91.7%/47.8% female, mean ± sd age 58.6 ± 13.2/54.0 ± 11.3 years) were analysed. The median (IQR) PROMIS PF-10 score was 34.5 (31.4-37.6) in RA and 36.0 (32.8-38.3) in axSpA patients. The PROMIS PF-10 correlated strongly with the HAQ-DI, BASFI, and EQ-5D-5L index score (r > 0.6), moderately with the SF-36 Physical Component Summary score, EQ-VAS, and 6MWT (0.30 ≤ r ≤ 0.60), and weakly with the SF-36 Mental Component Summary score (r < 0.30). Five of six hypotheses (83%) were confirmed in both groups. CONCLUSION: The overall strong correlation of the PROMIS PF-10 with measures of PF and moderate to weak correlations with outcomes measuring different constructs were confirmed in subpopulations of RA and axSpA patients with severe functional limitations, supporting its construct validity.

NT-proBNP and sRAGE levels in early rheumatoid arthritis.

OBJECTIVE: Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD: Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS: After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION: Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis.

OBJECTIVES: To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state. MATERIALS AND METHODS: A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies. RESULTS: Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (- 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups. CONCLUSION: We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.

Cost-effectiveness of five different anti-tumour necrosis factor tapering strategies in rheumatoid arthritis: a modelling study.

Objective: To investigate the cost-effectiveness of five different tumour necrosis factor inhibitor tapering strategies in patients with rheumatoid arthritis (RA) and stable low disease activity, using a modelling design.Method: Using Markov models based on data from the DRESS and STRASS randomized controlled trials, and the Nijmegen RA cohort, five tapering strategies for etanercept and adalimumab were tested against continuation: 1, four-step tapering (DRESS strategy); 2, five-step tapering; 3, tapering without withdrawal; 4, use of a stricter flare criterion; and 5, use of a theoretical predictor for successful tapering. We also examined how well a biomarker should be able to predict in order for strategy 5 to become cost-effective compared to the other strategies.Results: All examined tapering strategies were cost saving (range: EUR 5128 to 7873) but yielded more short-lived flares compared to continuation. The change in utilities compared to continuation was minimal and not clinically relevant (range: -0.005 to 0.007 quality-adjusted life-years). Strategy 1 was cost-effective compared to all other strategies [highest incremental net monetary benefit (iNMB)]. However, there was a large overlap in credible intervals, especially between strategies 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it is inexpensive and has a sensitivity and specificity of at least 84%.Conclusion: Because our study showed a comparable iNMB for tapering in four or five steps (including discontinuation), we recommend a choice between these strategies, based on shared decision making.

Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: combined results of three prospective cohort studies.

OBJECTIVE: To explore the associations between different histologically assessed, inflammatory synovial characteristics and subsequent clinical and structural aspects in knee osteoarthritis (OA). DESIGN: Knee OA patients, ranging in stage from early to advanced, were recruited from three different ongoing studies. Synovial tissue biopsies were taken and histologically assessed for six features (four inflammatory related aspects, fibrosis and fibrin deposition). Clinical aspects (WOMAC pain, functioning and stiffness and SF-36 vitality) and structural aspects (Kellgren and Lawrence (KL)-grade, joint space narrowing (JSN; 0-3) and osteophytes (0-3), and reception of total knee replacement (TKR)) were repeatedly assessed during follow-up. Associations between histology and clinical and structural aspects were analysed using linear mixed model analyses and cox proportional hazards analysis. RESULTS: Biopsies of 83 patients (median complaint duration: 5 [2-8] years) were analysed. Follow-up was a median of 1.4 [0.8-2.7] years for clinical and 1.8 [0.2-5.2] years for structural aspects. Fibrosis and fibrin deposition were inversely correlated with the inflammatory features. A higher fibrosis score was associated with a lower scores for KL-grade, JSN and osteophytes, while higher scores for perivascular oedema, synovial lining thickness and vascularisation were associated with higher scores for structural aspects during follow-up. No associations were found between each of the histological features and any of the clinical aspects or the chance for TKR during follow-up. CONCLUSIONS: Inflammatory related histological aspects are associated with subsequent increased radiological severity in knee OA, while fibrosis seems to protect against this, providing a potential therapeutic target for OA treatment.

Lack of beneficial effects of low-dose radiation therapy on hand osteoarthritis symptoms and inflammation: a randomised, blinded, sham-controlled trial.

OBJECTIVES: Low-dose radiation therapy (LDRT) is widely used as treatment for osteoarthritis (OA) in some countries, while relatively unknown in others. Systematic literature review displayed a lack of high-level evidence for beneficial effects in clinical practice. The aim was to assess the efficacy of LDRT on symptoms and inflammation in hand OA patients in a randomised, blinded, sham-controlled trial, using validated outcome measures. DESIGN: Hand OA patients, ≥50 years, with pain ≥5 (scale 0-10) and non-responding to conservative therapy were included and randomised 1:1 to receive LDRT (6 × 1 Gy in 2 weeks) or sham (6 × 0 Gy in 2 weeks). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months post-intervention. Secondary outcomes were pain and functioning (Australian/Canadian Hand Osteoarthritis Index; AUSCAN), quality of life (Short Form Health Survey; SF36) and inflammatory outcomes: erythrocyte sedimentation rate and C-reactive protein serum levels, effusion, synovial thickening and power Doppler signal on ultrasound (range 0-3). RESULTS: Fifty-six patients were included. After 3 months, no significant difference in responders was observed between groups (LDRT: 8 (29%); sham: 10 (36%); difference -7% (95%CI -31-17%)). Also, differences in clinical and inflammatory outcomes between groups were small and not significant. CONCLUSIONS: We were unable to demonstrate a substantial beneficial effect of LDRT on symptoms and inflammation in patients with hand OA, compared to sham treatment. Although a small effect can not be excluded, a treatment effect exceeding 20% is very unlikely, given the confidence interval. Therefore, in the absence of other high-level evidence, we advise against the use LDRT as treatment for patients with hand OA. CLINICAL TRIAL REGISTRATION NUMBER: NTR4574 (Dutch Trial Register).

[Polymyalgia rheumatica: new developments and challenges]. / Polymyalgia rheumatica.

- Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder in which inflammation markers, both erythrocyte sedimentation rate (ESR) and CRP values, are often elevated. However, a non-abnormal ESR or CRP value does not preclude the diagnosis.- PMR is an arbitrary diagnosis and presents both diagnostic and therapeutic challenges.- Imaging diagnostics, such as echography, MRI or FDG-PET/CT, may potentially be applied more frequently as a second-line investigation when there is doubt concerning the diagnosis. Currently these additional imaging techniques are not applied in first line diagnostics.- Glucocorticoids remain the cornerstone treatment for polymyalgia rheumatica. Often patients react swiftly to this, but in 29-45% of cases an effect is only observed 3-4 weeks later. The treatment course typically lasts 1-3 years.- More research has been conducted into potential glucocorticoid-sparing treatments. Most of the scientific evidence concerns the effectiveness of methotrexate; there is some evidence regarding the effectiveness of azathioprine and leflunomide. Tocilizumab, an IL-6 receptor inhibitor, has shown promise as a treatment, but further evidence is required.

Prediction of successful dose reduction or discontinuation of adalimumab, etanercept, or infliximab in rheumatoid arthritis patients using serum drug levels and antidrug antibody measurement.

BACKGROUND: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients. RESEARCH DESIGN AND METHODS: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1-1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined. RESULTS: No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23-0.49; cut-off <2.6 mg/l). In sub analyses, higher adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58-1.00; cut-off >7.8). ADAb were infrequent and not predictive of successful discontinuation. CONCLUSIONS: No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction.

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.

Choosing wisely in daily practice: a mixed methods study on determinants of antinuclear antibody testing by rheumatologists.

OBJECTIVES: To explore the relationship between antinuclear antibody (ANA) overuse and rheumatologist-related factors before and after an intervention aimed at reducing ANA overuse. METHOD: In this mixed methods study we performed surveys among rheumatologists (n = 20) before and after the ANA intervention (education and feedback). We identified clinician-related determinants of ANA overuse (demographic characteristics, cognitive bias, numeracy, personality, thinking styles, and knowledge) by multivariate analysis. Two focus group meetings with rheumatologists were held 6 months after the intervention to explore self-reported determinants. RESULTS: Questionnaires were completed by all rheumatologists and eight participated in the focus groups. Rheumatologists with more work experience and a less extravert personality ordered more ANA tests before the intervention [ß = 0.01, 95% confidence interval (CI) 0.003 to 0.02, p = 0.01 and ß = -0.11, 95% CI -0.21 to -0.01, p = 0.04, respectively; R2 = 47%]. After the intervention, female rheumatologists changed less than their male colleagues with regard to the number of ANA tests ordered (ß = 0.15, 95% CI 0.03-0.26, p = 0.02; R2 = 25%). During the focus groups, seven themes were identified that influenced improvement in ANA overuse: determinants related to the intervention and the study, individual health professionals, patients, professional interactions, incentives and resources, capacity for organizational change, and social, political, and legal factors. CONCLUSIONS: We identified several determinants that together explained a sizable part of the variance observed in the ANA outcomes at baseline and in the change in ANA outcomes afterwards. Furthermore, the focus groups yielded additional factors suggesting a complex interplay of determinants influencing rheumatologists' ANA ordering behaviour.

Implementation of protocolized tight control and biological dose optimization in daily clinical practice: results of a pilot study.

OBJECTIVES: To assess the effects of education, guideline development, and individualized treatment advice on rheumatologist adherence to tight control-based treatment and biological dose optimization in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthropathy (SpA) patients. METHOD: This pilot study, among two rheumatologists and two specialized nurses in a general hospital, combined education, feedback, local guideline development, and individualized treatment advice. Outcomes (baseline and 1 year post-intervention) were the percentage of patients with a Disease Activity Score in 28 joints (DAS28) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured during the visit, mean DAS28/BASDAI, and the percentage of patients using a reduced biological dose. DAS28 outcomes only applied to RA and PsA patients, BASDAI outcomes only applied to SpA patients whereas outcomes on biological dose applied to all patients. RESULTS: A total of 232 patients (67% RA, 15% PsA, 18% SpA; 58% female, mean age 56 ± 15 years) were included in the study. The percentage of DAS28 and BASDAI measurements performed increased after the intervention [DAS28 15-51%, odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.5; BASDAI 23-50%, OR 2.2, 95% CI 1.0-5.5], with mean DAS28 and BASDAI scores remaining similar (DAS28: mean difference 0.1, 95% CI -0.3 to 0.5; BASDAI: mean difference 0.03, 95% CI -1.8 to 1.9). Use of a reduced biological dose increased from 10% to 61% (OR 3.9, 95% CI 2.4-6.5). CONCLUSIONS: A multicomponent intervention strategy aimed at rheumatologists can lead to improved adherence to tight control-based treatment and a reduction in the use of biologicals in RA, SpA, and PsA patients.

Practice what you preach? An exploratory multilevel study on rheumatoid arthritis guideline adherence by rheumatologists.

OBJECTIVES: To assess variation in and determinants of rheumatologist guideline adherence in patients with rheumatoid arthritis (RA), in daily practice. METHODS: In this retrospective observational study, guideline adherence in the first year of treatment was assessed for 7 predefined parameters on diagnostics, treatment and follow-up in all adult patients with RA with a first outpatient clinic visit at the study centre, from September 2009 to March 2011. Variation in guideline adherence was assessed on parameter and rheumatologist level. Determinants for guideline adherence were assessed in patients (demographic characteristics, rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (aCCP) positivity, erythrocyte sedimentation rate, erosive disease, comorbidity and the number of available disease modifying anti-rheumatic drug (DMARD) treatment options) and rheumatologists (demographic and practice characteristics, guideline knowledge and agreement, outcome expectancy, cognitive bias, thinking style, numeracy and personality). RESULTS: A total of 994 visits in 137 patients with RA were reviewed. Variation in guideline adherence among parameters was present (adherence between 21% and 72%), with referral to the physician assistant as lowest scoring and referral to a specialised nurse as highest scoring parameter. Variation in guideline adherence among rheumatologists was also present (adherence between 22% and 100%). Patient sex, the number of DMARD options, presence of erosions, comorbidity, RF/aCCP positivity, type of patient and the rheumatologists' scientific education status were associated with adherence to 1 or more guideline parameters. CONCLUSIONS: Guideline adherence varied considerably among the guideline parameters and rheumatologists, showing that there is room for improvement. Guideline adherence in our sample was related to several patient and rheumatologist determinants.

No relevant excess prevalence of myotonic dystrophy type 2 in patients with suspected fibromyalgia syndrome.

Myotonic dystrophy type 2 (DM2) is a rare, autosomal dominant, multisystem disorder with proximal weakness, myotonia, pain and cataract as important symptoms. Given the assumed underreporting of DM2 in the Netherlands combined with the predominant role of pain in DM2 as well as in fibromyalgia syndrome (FMS), we hypothesized there will be an excess prevalence of DM2 in patients with (suspected) FMS. Our objective was to determine the prevalence of DM2 in patients with suspected FMS. A prevalence of 2% was considered a relevant excess frequency. Between November 2011 and April 2014, 398 patients with suspected FMS who had been assessed by a rheumatologist participated in this cross-sectional study. 95% of the study population was female, with a mean age of 42 years. The final ICD-9 diagnoses were collected, in 96% the diagnosis was FMS. 92% met the 2010 American College of Rheumatology (ACR) diagnostic criteria for FMS. A questionnaire including neuromuscular symptoms was completed. Creatine kinase was determined, and genetic testing for DM2 was conducted in all patients. DM2 was established in only one patient (0.25%, 95% CI 0.04-1.4%), thus disapproving our hypothesis of a relevant prevalence of 2%. Our results suggest that patients with suspected FMS should not routinely be tested for DM2.

Responsiveness of four patient-reported outcome measures to assess physical function in patients with knee osteoarthritis.

OBJECTIVES: The aim of this study was to evaluate the responsiveness of four patient-reported outcome measures (PROMs) to measure change in physical function simultaneously in patients with knee osteoarthritis (OA) following currently recommended COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) standards. METHOD: Patients with knee OA receiving conservative treatment following a stepped care approach were invited to complete a set of questionnaires at baseline and 3 months. Questionnaires included four widely used measures of physical function: the Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), the Lequesne algofunctional index (LAI), the Lower Extremity Functional Scale (LEFS), and the Western Ontario and McMaster University Osteoarthritis Index Physical Function subscale (WOMAC-PF). Responsiveness of physical function was investigated according to the COSMIN standards by testing 15 a priori defined hypotheses. Responsiveness was considered positive if > 75% of the hypotheses could be confirmed. RESULTS: A total of 161 patients participated [61% female, mean (sd) age 59 (9) years and body mass index 29.7 (5.0) kg/m2]. Baseline values of the four PROMs were, mean (sd): KOOS-PS 53.6 (16.8), LAI 11.0 (4.0), LEFS 40.6 (14.1), and WOMAC-PF 51.8 (19.4). We could confirm 12 out of 15 predefined hypotheses (80%) about expected correlations for the WOMAC-PF whereas for the KOOS-PS, LAI, and LEFS < 75% hypotheses could be confirmed (73, 67, and 73%. respectively). CONCLUSIONS: Our results suggest that the WOMAC-PF is able to detect changes over time in physical function and therefore should be the measure of first choice in clinical trials evaluating the effectiveness of an intervention on physical function in knee OA patients.

The efficacy and safety of low-dose radiotherapy on pain and functioning in patients with osteoarthritis: a systematic review.

Low-dose radiotherapy (LD-RT) has been widely used for treatment of non-malignant disorders since its introduction and animal studies show anti-inflammatory effects in osteoarthritis (OA). However, the evidence for its effect in clinical practice remains unclear. Therefore, the aim of this study is to systematically summarise the literature on effectiveness of LD-RT on pain and functioning in patients with OA and its safety. Broad search terms were used to search PubMed, EMBASE and Web of Science. Primary inclusion criteria were osteoarthritis as indication, radiotherapy as intervention, written in English, German or Dutch and published since 1980. Study quality was assessed using the EPHPP Quality Assessment Tool for Quantitative Studies (scale: strong, moderate, weak). Seven studies were suitable for inclusion, all with retrospective uncontrolled observational design. Methodological quality of all studies was judged as weak. Most studies used 2-3 RT sessions per week for 2 weeks, some with booster session after 6 weeks. Generally, non-validated single-item measurement instruments were used to evaluate the effect of LD-RT on pain and function. Across the studies, in 25-90 and 29-71 % of the patients pain and functioning improved, respectively. Side effects were described in one study, none were reported. Our results show that there is insufficient evidence for efficacy or to confirm the safety of LD-RT in treatment of OA, due to absence of high-quality studies. Therefore, a well-designed, sham-controlled and blinded randomised trial, using validated outcome measures is warranted to demonstrate the value of LD-RT for OA in clinical practice.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms.

OBJECTIVES: Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. RESULTS: Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosmer-Lemeshow test results indicated that all three algorithms provided poor model fit (p<0.05) for the Nijmegen and external validation cohort. The adapted SCORE algorithm mainly improves CVD risk estimation in non-event cases and does not show a clear advantage in reclassifying patients with RA who develop CVD (event cases) into more appropriate risk groups. CONCLUSIONS: This study demonstrates for the first time that adaptations of the SCORE algorithm do not provide sufficient improvement in risk prediction of future CVD in RA to serve as an appropriate alternative to the original SCORE. Risk assessment using the original SCORE algorithm may underestimate CVD risk in patients with RA.

Randomized trial of the effectiveness of a non-pharmacological multidisciplinary face-to-face treatment program on daily function compared to a telephone-based treatment program in patients with generalized osteoarthritis.

OBJECTIVE: To compare the effectiveness of a non-pharmacological multidisciplinary face-to-face self-management treatment program with a telephone-based program on daily function in patients with generalized osteoarthritis (GOA). DESIGN: A pragmatic single-blind randomized clinical superiority trial involving 147 patients clinically diagnosed with GOA, randomly allocated to either a 6 week non-pharmacological multidisciplinary face-to-face treatment program comprising seven group sessions or a 6 week telephone-based treatment program comprising two group sessions combined with four telephone contacts. Both programs aimed to improve daily function and to enhance self-management to control the disease. The programs critically differed in mode of delivery and intensity. Daily function (primary outcome) and secondary outcomes were assessed at baseline, 6, 26 and 52 weeks. Data were analyzed using linear or logistic multilevel regression models corrected for baseline, sex and group-wise treatment. RESULTS: No differences in effectiveness between both treatment programs were observed on the primary outcome (group difference (95% CI): -0.03 (-0.14, 0.07)) or on secondary outcome measures, except for a larger improvement in pain in the face-to-face treatment group (group difference (95% CI): 1.61 (0.01, 3.21)). Within groups, significant improvements were observed on several domains, especially in the face-to-face group. However, these benefits are relatively small and unlikely to be of clinical importance. CONCLUSIONS: We found no differences in treatment effect between patients with GOA who followed a non-pharmacological multidisciplinary face-to-face self-management program and those who received a telephone-delivered program. Besides, our findings demonstrated limited benefits of a self-management program for individuals with GOA. Dutch Trial Register trial number: NTR2137.