Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden. METHODS: We conducted a randomised, double-blind, placebo-controlled, proof-of-concept-trial at the Leiden University Medical Centre, Leiden, Netherlands. Adults aged 18 years or older with arthralgia clinically suspected of progressing to rheumatoid arthritis and MRI-detected subclinical joint inflammation were eligible for enrolment across 13 rheumatology outpatient clinics in the southwest region of the Netherlands and randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a 1-year course of oral methotrexate (up to 25 mg/week), or placebo (single injection and tablets for 1 year). Participants and investigators were masked to group assignment. Follow-up continued for 1 year after the end of the 1-year treatment period. The primary endpoint was development of clinical arthritis (fulfilling the 2010 rheumatoid arthritis classification criteria or involving two or more joints) that persisted for at least 2 weeks. Patient-reported physical functioning, symptoms, and work productivity were secondary endpoints, which were measured every 4 months. Additionally, the course of MRI-detected inflammation was studied. All participants entered the intention-to-treat analysis. This trial is registered with EudraCT, 2014-004472-35, and the Netherlands Trial Register, NTR4853-trial-NL4599. FINDINGS: Between April 16, 2015, and Sept 11, 2019, 901 patients were assessed for eligibility and 236 were enrolled and randomly assigned to active treatment (n=119) or placebo (n=117). At 2 years, the frequency of the primary endpoint was similar between the groups (23 [19%] of 119 participants in the treatment group vs 21 [18%] of 117 in the placebo group; hazard ratio 0·81, 95% CI 0·45 to 1·48). Physical functioning improved more in the treatment group during the first 4 months and remained better than in the placebo group (mean between-group difference in Health Assessment Questionnaire disability index over 2 years: -0·09, 95% CI -0·16 to -0·03; p=0·0042). Similarly, pain (on scale 0-100, mean between-group difference: -8, 95% CI -12 to -4; p<0·0001), morning stiffness of joints (-12, -16 to -8; p<0·0001), presenteeism (-8%, -13 to -3; p=0·0007), and MRI-detected joint inflammation (-1·4 points, -2·0 to -0·9; p<0·0001) showed sustained improvement in the treatment group compared with the placebo group. The number of serious adverse events was equal in both groups; adverse events were consistent with the known safety profile for methotrexate. INTERPRETATION: Methotrexate, the cornerstone treatment of rheumatoid arthritis, initiated at the pre-arthritis stage of symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as shown by sustained improvement in MRI-detected inflammation, related symptoms, and impairments compared with placebo. FUNDING: Dutch Research Council (NWO; Dutch Arthritis Society).

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.

BACKGROUND: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. METHODS: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. RESULTS: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies. CONCLUSION: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

An updated matrix to predict rapid radiographic progression of early rheumatoid arthritis patients: pooled analyses from several databases.

OBJECTIVE: In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. METHODS: Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. RESULTS: 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). CONCLUSION: A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

Determinants of reaching drug-free remission in patients with early rheumatoid or undifferentiated arthritis after one year of remission-steered treatment.

OBJECTIVE: The aim of this study was to assess whether baseline characteristics in patients with undifferentiated arthritis or early RA affect the possibility of achieving drug-free remission after 1 year (DFR1 year) of early remission induction therapy. METHODS: We included 375 patients participating in the IMPROVED study who achieved remission (DAS < 1.6) after 4 months (early remission) and were by protocol able to achieve DFR1 year. Having started with MTX plus prednisone, patients tapered prednisone to zero; after 8 months, those still in remission tapered MTX to zero, while those not in remission restarted prednisone. Characteristics of patients achieving and not achieving DFR1 year were compared. Logistic regression was performed to identify predictors of DFR1 year. RESULTS: After 1 year, 119 patients (32%) were in DFR. Presence of RF, fulfilling the 2010 criteria for RA, and a low tender joint count were associated with achieving DFR1 year, whereas presence of ACPA was not. None of the baseline characteristics was independently associated with DFR1 year. DFR1 year was sustained for 4 months in 65% of the patients. ACPA-positive patients less often had sustained DFR than ACPA-negative patients (58% vs 80%, P = 0.013). CONCLUSION: After 1 year of remission-steered treatment, 32% of the patients who had achieved early remission after 4 months were able to taper medication and achieved DFR. Neither the presence of ACPA nor any other baseline characteristics were independently associated with achieving DFR1 year, but in ACPA-positive patients DFR was less often sustained.

Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study).

OBJECTIVE: To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo. METHODS: 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)). RESULTS: 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment. CONCLUSIONS: After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.

'Every picture tells a story': Interviews and diaries with children with cerebral palsy about adapted cycling.

AIMS: The study aims to explore the effect of participation in adapted cycling on quality of life for children with cerebral palsy (CP). METHODS: The study used a qualitative approach developing creative mosaic methods using interviews and diaries. This study had two groups of children with CP: those who participated in adapted cycling and a control group who had not yet started. Children with CP aged 2-17 years who were already cycling were invited to take part in two interviews at the beginning and end of a 6-week period and keep a cycling diary during this time. The control group of children with CP aged 2-17 years were asked to keep a diary of physical activities over 6 weeks and to take part in one interview at the end. Welsh, English, Bengali and Arabic were the languages spoken, and some children used communication aids. RESULTS: Results presented here include the first 25 children's interviews and diaries. The emergent themes from the analysis are: learning a new skill, the impact on wider family and friends, social participation and future aspirations. The diaries added an emotional dimension, by illustrations drawn by the children. CONCLUSION: The children who took part in adapted cycling enjoyed this experience and it improved their sense of well-being. Some in the control group went on to participate in adapted cycling. Physiotherapists can carry out creative research to hear the voices of children and young people with CP and incorporate their views and ideas into the development of service model delivery and treatment programmes.

Personalized medicine: predicting responses to therapy in patients with RA.

Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine. The identification of predictors of response is the first step toward this. In rheumatoid arthritis (RA), several prediction matrices were designed to predict the risk of rapid radiological progression (RRP) in the first year of treatment, on either disease modifying anti-rheumatic drug (DMARD) monotherapy or combination therapy with prednisone or a biological agent. Both clinical markers and biomarkers of response to either anti-TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies. Most of these markers need validation in other cohorts. Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA.

Adapted bikes: what children and young people with cerebral palsy told us about their participation in adapted dynamic cycling.

PURPOSE: Children and young people with Cerebral Palsy have limited opportunities for participation and there has been limited research to explore this concept. Adapted dynamic cycling (ADC) is one activity that can enable them to participate in the community. The aim of this paper is to report the views and experiences of children and young people with CP and their families regarding their participation in ADC. METHODS: This was part of a mixed methods study of which the qualitative findings are reported here. Iterative creative methods were developed which involved semi-structured interviews and diaries about the ADC experience. RESULTS: The themes that emerged were the staff and the environment at the cycling hire project, the facilitators and barriers to ADC, the technical set up of the bike and the impact on the child and family in terms of developments over time, future aspirations, learning cycling skills, social participation and health benefits. CONCLUSIONS: The data showed that children's experiences of ADC were fun and enjoyable. This fun exercise should be incorporated into a physiotherapy programme as part of the child or young person with CP's rehabilitation. Policy makers and parents may find the information useful to increase the child's participation.

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study.

INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-16.

Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study).

AIM: Classifying more patients as rheumatoid arthritis (RA) (2010 American College of Rheumatology/European League Against Rheumatism criteria for RA) may improve treatment outcomes but may cause overtreatment in daily practice. The authors determined the efficacy of initial methotrexate (MTX) plus prednisone treatment in patients with 1987 or 2010 classified RA and undifferentiated arthritis (UA). METHOD: 610 recent onset RA or UA patients started with MTX 25 mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks. Percentage remissions after 4 months were compared between RA (1987 or 2010 criteria) and UA. Predictors for remission were identified. RESULTS: With the 2010 criteria, 19% more patients were classified as RA than with the 1987 criteria, but similar remission rates were achieved: 291/479 (61%) 2010 classified RA and 211/264 (58%) 1987 classified RA patients (p=0.52), and 79/122 (65%) UA patients (p=0.46). Anticitrullinated protein antibodies (ACPA) positive RA patients achieved more remission (66%) than ACPA negative RA patients (51%, p=0.001), but also had a lower mean baseline Disease Activity Score (DAS) (3.2 vs 3.6, p<0.001). Independent predictors for remission were male sex, low joint counts, DAS and Health Assessment Questionnaire, low body mass index and ACPA positivity. CONCLUSION: Initial treatment with MTX and a tapered high dose of prednisone results in similarly high remission percentages after 4 months (about 60%) in RA patients, regardless of fulfilling the 1987 or 2010 criteria, and in UA patients. Independent predictors indicate that initiating treatment while disease activity is relatively low results in more remission.

Sustained drug-free remission in rheumatoid arthritis after DAS-driven or non-DAS-driven therapy: a comparison of two cohort studies.

OBJECTIVES: To compare the prevalence of and predictors for sustained drug-free remission in two cohorts of patients with recent-onset RA treated with DAS-driven therapy or non-DAS-driven therapy. METHODS: Sustained drug-free remission was assessed after 5 years of follow-up in 508 patients treated with DAS-driven therapy (DAS ≤ 2.4) in a randomized treatment cohort, and in 424 patients who received non-DAS-driven therapy in a prospective inception cohort. The design of the DAS-driven cohort required systematic joint assessments with DAS-driven restart of therapy. Predictors for remission were identified by univariable and multivariable logistic regression in each cohort separately and in a combined multivariate logistic regression analysis corrected for propensity scores, including a sensitivity analysis on patients receiving initial monotherapy. RESULTS: Patients in the DAS-driven cohort had more active disease at baseline, but the prevalence of sustained drug-free remission was similar after DAS-driven (9.8%) and non-DAS-driven therapy (10.6%). Among patients with ACPA, drug-free remission was more frequently achieved after DAS-driven than after non-DAS-driven therapy (5.4 vs. 2.1%, OR = 2.68, 95% CI 0.97, 7.43). Absence of ACPA and short symptom duration were independent predictors for sustained drug-free remission in both cohorts. Initial treatment choice and inclusion period were not predictive. The sensitivity analysis yielded comparable results. CONCLUSION: Retrospectively comparing a DAS-driven to a non-DAS-driven therapy cohort, the occurrence and predictors of sustained drug-free remission were similar. The DAS-driven cohort had a more unfavourable prognosis. DAS-driven therapy may improve the chance of sustained drug-free remission in ACPA-positive patients with recent-onset RA.

A comparison of subgroup analyses in grant applications and publications.

In this paper, the authors compare subgroup analyses as outlined in grant applications and their related publications. Grants awarded by the Netherlands Organization for Health Research and Development (ZonMw) from 2001 onward that were finalized before March 1, 2010, were studied. Of the 79 grant proposals, 50 (63%) were intervention studies, 18 (23%) were diagnostic studies, and 6 (8%) were prognostic studies. Subgroups were mentioned in 49 (62%) grant applications and in 53 (67%) publications. In 20 of the 79 projects (25%), the publications were completely in agreement with the grant proposal; that is, subgroups that were prespecified in the grant proposal were reported and no new subgroup analyses were introduced in the publications. Of the 149 prespecified subgroups, 46 (31%) were reported in the final report or scientific publications, and 143 of the 189 (76%) reported subgroups were based on post-hoc findings. For 77% of the subgroup analyses in the publications, there was no mention of whether these were prespecified or post hoc. Justification for subgroup analysis and methods to study subgroups were rarely reported. The authors conclude that there is a large discrepancy between grant applications and final publications regarding subgroup analyses. Both nonreporting prespecified subgroup analyses and reporting post-hoc subgroup analyses are common. More guidance is clearly needed.

Validity of the disease activity score in undifferentiated arthritis.

OBJECTIVE: To study whether the Disease Activity Score (DAS) is a valid measure of disease activity in undifferentiated arthritis (UA). METHODS: Data from a randomized, double-blind, placebo-controlled trial of methotrexate (MTX) and placebo involving 110 patients with UA were used. Data included baseline and 3, 6, 9, and 12 months, as well as diagnosis at 18 months. Validity of the DAS was analyzed using factor analysis, correlations with disease activity variables, correlations with changes in disability and joint damage, differences in DAS between diagnoses, and detecting the difference between placebo and MTX. RESULTS: Three disease activity factors were retrieved from the disease activity variables: patient reported outcomes, tender and swollen joints, and acute phase reactants. The DAS had its highest correlations (r > 0.77) with tender joint counts, followed by swollen joint counts (r > 0.63) and patient reported outcomes (r > 0.30), but the DAS correlated less with C-reactive protein levels (r = 0.32). Over time, the DAS was related to the Health Assessment Questionnaire response with an odds ratio of 4.1 (95% confidence interval 2.1-8.0), but not with change in joint damage. At 18 months, the mean DAS was 2.6 for rheumatoid arthritis patients, 2.2 for UA patients, and 1.9 for patients in remission (P = 0.001). The DAS discriminated better than all single variables between MTX and placebo, with a Guyatt's effect size of 0.89. CONCLUSION: The DAS appears to be a reasonably valid measure of disease activity for use in UA clinical trials.

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). METHODS: The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. RESULTS: In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). CONCLUSION: This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.

Interobserver agreement for the interpretation of contrast-enhanced 3D MR angiography and MDCT angiography in peripheral arterial disease.

OBJECTIVE: The objective of our study was to compare interobserver agreement for interpretations of contrast-enhanced 3D MR angiography and MDCT angiography in patients with peripheral arterial disease. SUBJECTS AND METHODS: Of 226 eligible patients, 69 were excluded. The remaining 157 consecutive patients were prospectively randomized to either MR angiography (n = 78) or MDCT angiography (n = 79). Two observers independently evaluated for arterial stenosis or occlusion on MR angiography (2,157 segments) and MDCT angiography (2,419 segments) using a 5-point ordinal scale. Vessel wall calcifications were noted. Interobserver agreement for each technique was evaluated with a weighted kappa (kappa(w)) statistic. RESULTS: Although interobserver agreement for both was excellent, the interobserver agreement for MR angiography (kappa(w) = 0.90; 95% confidence interval [CI], 0.89-0.92) was higher than that for MDCT angiography (kappa(w) = 0.85; 95% CI, 0.83-0.86) for reporting the degree of arterial stenosis or occlusion in all segments. For the different anatomic locations, the interobserver agreement for MR angiography versus MDCT angiography was as follows: aortoiliac (kappa(w) =0.91 vs 0.84, respectively), femoropopliteal (kappa(w) = 0.91 vs 0.87), and crural (kappa(w) = 0.90 vs 0.83) segments. The interobserver agreement of MDCT angiography significantly decreased in the presence of calcifications but was still good for all anatomic locations. The lowest agreement was found for crural segments in the presence of calcifications (kappa(w) = 0.67). With MR angiography, there were 12 times more nondiagnostic segments than with MDCT angiography (81 vs 7, respectively). CONCLUSION: Interpretations of MR angiography and MDCT angiography for peripheral arterial disease have an excellent interobserver agreement. MR angiography has a higher interobserver agreement than MDCT angiography, and the presence of calcified segments significantly decreases interobserver agreement for MDCT angiography.

Contrast-enhanced MR angiography and digital subtraction angiography in living renal donors: diagnostic agreement, impact on decision making, and costs.

OBJECTIVE: The objective of our study was to evaluate the diagnostic agreement, the impact on decision making, and the costs of contrast-enhanced MR angiography and digital subtraction angiography in the workup of living renal donors. CONCLUSION: Contrast-enhanced MR angiography for the preoperative evaluation of renal donors is superior to digital subtraction angiography in revealing vascular anomalies and depicting parenchymal abnormalities and is less costly; furthermore, it does not lead to preoperative decisions that differ from those based on digital subtraction angiography. If contrast-enhanced MR angiography does not provide sufficient information to make a confident decision, an additional digital subtraction angiography examination should be performed.

Peripheral arterial disease: sensitivity-encoded multiposition MR angiography compared with intraarterial angiography and conventional multiposition MR angiography.

A sensitivity-encoded magnetic resonance (MR) angiography protocol was developed in which imaging times in the pelvic and upper-leg positions were reduced and isotropic submillimeter voxel volumes were acquired in the lower-leg position. To achieve this, sensitivity encoding and random central-k-space segmentation in a centric filling order were applied. Results with this technique were compared with those with midstream aortic digital subtraction angiography (DSA) (as the reference standard) and conventional MR angiography in 15 patients with peripheral vascular disease. The results show that sensitivity-encoded MR angiography demonstrates increased diagnostic accuracy in comparison to that with conventional MR angiography and depicts more open infragenual arterial segments compared with both midstream aortic DSA and conventional MR angiography.

Cost-effectiveness targets for multi-detector row CT angiography in the work-up of patients with intermittent claudication.

PURPOSE: To determine the costs, sensitivity for detection of significant stenoses, and proportion of equivocal multi-detector row computed tomographic (CT) angiography results in the work-up of patients with intermittent claudication that would make this imaging examination cost-effective compared with gadolinium-enhanced magnetic resonance (MR) angiography. MATERIALS AND METHODS: A decision model was used to compare the societal cost-effectiveness of a new imaging modality with that of gadolinium-enhanced MR angiography. Main outcome measures were quality-adjusted life years (QALYs) and lifetime costs. By using threshold analysis of a given willingness to pay per QALY, target values for costs, sensitivity for detection of significant stenoses, and proportion of cases requiring additional work-up with intraarterial digital subtraction angiography owing to equivocal results of the new modality were determined. The base case evaluated was that of 60-year-old men with severe intermittent claudication and assumed an incremental cost-effectiveness threshold of 100,000 US dollars per QALY. RESULTS: If treatment were limited to angioplasty, a new imaging modality would be cost-effective if the costs were 300 US dollars and the sensitivity was 85%, even if up to 35% of patients needed additional work-up. When both angioplasty and bypass surgery were considered as treatment options, a new imaging modality was cost-effective if the costs were 300 US dollars, the sensitivity was higher than 94%, and 20% of patients required additional work-up. CONCLUSION: Multi-detector row CT angiography, as compared with currently used imaging modalities such as MR angiography, has the potential to be cost-effective in the evaluation of patients with intermittent claudication.

Pretreatment imaging workup for patients with intermittent claudication: a cost-effectiveness analysis.

PURPOSE: To determine the optimal imaging strategy in pretreatment workup of patients with intermittent claudication with use of noninvasive imaging modalities and intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: A decision-analytic model that considered test characteristics such as sensitivity, complications induced by the test, implications of missing lesions, and the consequences of overtreating patients, was developed to evaluate the societal cost-effectiveness (CE) of magnetic resonance (MR) angiography, duplex ultrasonography (US), and DSA. Our main outcome measures were quality-adjusted life years (QALYs), lifetime costs (in dollars), and incremental CE ratios. The base-case analysis considered a cohort of 60-year old male patients without a history of coronary artery disease who presented with severe claudication to undergo pretreatment imaging workup. RESULTS: The range in effectiveness and lifetime costs among different diagnostic workup strategies was small (largest difference in effectiveness: 0.025 QALYs; largest difference in lifetime costs: $1,800). If treatment was limited to angioplasty in patients with suitable lesions, MR angiography had an incremental CE ratio of $35,000 per QALY compared with no diagnostic workup, and DSA had an incremental CE ratio of $471,000 per QALY compared with MR angiography. If treatment options included both angioplasty and bypass surgery, DSA had an incremental CE ratio of $179,000 per QALY compared with no diagnostic workup, and MR angiography and duplex US were less effective and more costly. CONCLUSIONS: The differences in costs and effectiveness among diagnostic imaging strategies for patients with intermittent claudication are slight and MR angiography or duplex US can replace DSA without substantial loss in effectiveness and with a slight cost reduction.

Living renal donors: optimizing the imaging strategy--decision- and cost-effectiveness analysis.

PURPOSE: To determine the most cost-effective strategy for preoperative imaging performed in potential living renal donors. MATERIALS AND METHODS: In a decision-analytic model, the societal cost-effectiveness of digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography, contrast material-enhanced spiral computed tomographic (CT) angiography, and combinations of these imaging techniques was evaluated. Outcome measures included lifetime cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A base-case analysis was performed with a 40-year-old female donor and a 40-year-old female recipient. RESULTS: For the donor, MR angiography (24.05 QALYs and 9,000 dollars) dominated all strategies except for MR angiography with CT angiography, which had an incremental ratio of 245,000 dollars per QALY. For the recipient, DSA and DSA with MR angiography yielded similar results (10.46 QALYs and 179,000 dollars) and dominated all other strategies. When results for donor and recipient were combined, DSA dominated all other strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a 99% specificity or less for detection of renal disease, MR angiography with CT angiography was superior (34.47 QALYs and 190,000 dollars). CONCLUSION: For preoperative imaging in a potential renal donor, DSA is the most cost-effective strategy if it has a specificity greater than 99% for detection of renal disease; otherwise, MR angiography with CT angiography is the most cost-effective strategy.