scholarly journals Intensive therapy for moderate established rheumatoid arthritis: the TITRATE research programme

2021 ◽  
Vol 9 (8) ◽  
pp. 1-186
Author(s):  
David L Scott ◽  
Fowzia Ibrahim ◽  
Harry Hill ◽  
Brian Tom ◽  
Louise Prothero ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Confidence Interval ◽  
Systematic Reviews ◽  
Observational Studies ◽  
Standard Care ◽  
Health Assessment ◽  
Intensive Management ◽  
Established Rheumatoid Arthritis ◽  
Assessment Questionnaire

Background Rheumatoid arthritis is a major inflammatory disorder and causes substantial disability. Treatment goals span minimising disease activity, achieving remission and decreasing disability. In active rheumatoid arthritis, intensive management achieves these goals. As many patients with established rheumatoid arthritis have moderate disease activity, the TITRATE (Treatment Intensities and Targets in Rheumatoid Arthritis ThErapy) programme assessed the benefits of intensive management. Objectives To (1) define how to deliver intensive therapy in moderate established rheumatoid arthritis; (2) establish its clinical effectiveness and cost-effectiveness in a trial; and (3) evaluate evidence supporting intensive management in observational studies and completed trials. Design Observational studies, secondary analyses of completed trials and systematic reviews assessed existing evidence about intensive management. Qualitative research, patient workshops and systematic reviews defined how to deliver it. The trial assessed its clinical effectiveness and cost-effectiveness in moderate established rheumatoid arthritis. Setting Observational studies (in three London centres) involved 3167 patients. These were supplemented by secondary analyses of three previously completed trials (in centres across all English regions), involving 668 patients. Qualitative studies assessed expectations (nine patients in four London centres) and experiences of intensive management (15 patients in 10 centres across England). The main clinical trial enrolled 335 patients with diverse socioeconomic deprivation and ethnicity (in 39 centres across all English regions). Participants Patients with established moderately active rheumatoid arthritis receiving conventional disease-modifying drugs. Interventions Intensive management used combinations of conventional disease-modifying drugs, biologics (particularly tumour necrosis factor inhibitors) and depot steroid injections; nurses saw patients monthly, adjusted treatment and provided supportive person-centred psychoeducation. Control patients received standard care. Main outcome measures Disease Activity Score for 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR)-categorised patients (active to remission). Remission (DAS28-ESR < 2.60) was the treatment target. Other outcomes included fatigue (measured on a 100-mm visual analogue scale), disability (as measured on the Health Assessment Questionnaire), harms and resource use for economic assessments. Results Evaluation of existing evidence for intensive rheumatoid arthritis management showed the following. First, in observational studies, DAS28-ESR scores decreased over 10–20 years, whereas remissions and treatment intensities increased. Second, in systematic reviews of published trials, all intensive management strategies increased remissions. Finally, patients with high disability scores had fewer remissions. Qualitative studies of rheumatoid arthritis patients, workshops and systematic reviews helped develop an intensive management pathway. A 2-day training session for rheumatology practitioners explained its use, including motivational interviewing techniques and patient handbooks. The trial screened 459 patients and randomised 335 patients (168 patients received intensive management and 167 patients received standard care). A total of 303 patients provided 12-month outcome data. Intention-to-treat analysis showed intensive management increased DAS28-ESR 12-month remissions, compared with standard care (32% vs. 18%, odds ratio 2.17, 95% confidence interval 1.28 to 3.68; p = 0.004), and reduced fatigue [mean difference –18, 95% confidence interval –24 to –11 (scale 0–100); p < 0.001]. Disability (as measured on the Health Assessment Questionnaire) decreased when intensive management patients achieved remission (difference –0.40, 95% confidence interval –0.57 to –0.22) and these differences were considered clinically relevant. However, in all intensive management patients reductions in the Health Assessment Questionnaire scores were less marked (difference –0.1, 95% confidence interval –0.2 to 0.0). The numbers of serious adverse events (intensive management n = 15 vs. standard care n = 11) and other adverse events (intensive management n = 114 vs. standard care n = 151) were similar. Economic analysis showed that the base-case incremental cost-effectiveness ratio was £43,972 from NHS and Personal Social Services cost perspectives. The probability of meeting a willingness-to-pay threshold of £30,000 was 17%. The incremental cost-effectiveness ratio decreased to £29,363 after including patients’ personal costs and lost working time, corresponding to a 50% probability that intensive management is cost-effective at English willingness-to-pay thresholds. Analysing trial baseline predictors showed that remission predictors comprised baseline DAS28-ESR, disability scores and body mass index. A 6-month extension study (involving 95 intensive management patients) showed fewer remissions by 18 months, although more sustained remissions were more likley to persist. Qualitative research in trial completers showed that intensive management was acceptable and treatment support from specialist nurses was beneficial. Limitations The main limitations comprised (1) using single time point remissions rather than sustained responses, (2) uncertainty about benefits of different aspects of intensive management and differences in its delivery across centres, (3) doubts about optimal treatment of patients unresponsive to intensive management and (4) the lack of formal international definitions of ‘intensive management’. Conclusion The benefits of intensive management need to be set against its additional costs. These were relatively high. Not all patients benefited. Patients with high pretreatment physical disability or who were substantially overweight usually did not achieve remission. Future work Further research should (1) identify the most effective components of the intervention, (2) consider its most cost-effective delivery and (3) identify alternative strategies for patients not responding to intensive management. Trial registration Current Controlled Trials ISRCTN70160382. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 8. See the NIHR Journals Library website for further project information.

scholarly journals P88 Intensive management in moderate established rheumatoid arthritis: the titrate trial

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Elena Nikiphorou ◽  
on behalf of the ◽  
TITRATE Programme Investigators
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Motivational Interviewing ◽  
Standard Care ◽  
Cost Effective ◽  
Treat To Target ◽  
Intensive Management ◽  
Remission Rates ◽  
Interviewing Techniques

Abstract Background Intensive management (IM) using treat-to-target principles has been shown to be effective in many trials of early rheumatoid arthritis (RA) in patients with high disease activity levels. There is no trial evidence that this approach benefits patients with moderately active RA - a dominant group in clinics. We tested the hypothesis that IM increases remission rates in established moderate RA patients (DAS28-ESR 3.2-5.1) receiving stable conventional synthetic disease modifying drugs (csDMARDs) compared to standard care (SC). IM comprised of: (a)monthly clinical assessments; (b)treat-to-target titrated medication including biologics; (c)psycho-social support delivered by trained nurses and other practitioners in motivational interviewing techniques. Methods A multicentre individually randomised trial compared IM (using combination DMARDs, depot steroid, biologics in non-responders, alongside supportive care using motivational interviewing techniques from trained nurses) to standard care (SC) patients receiving their usual clinical care. The primary outcome was 12-months remission by DAS28-ESR. Secondary outcomes: alternative remission assessments, disability via the health assessment questionnaire (HAQ), pain, fatigue, erosive progression and harm. Multivariable logistic and linear regression compared treatment approaches under intention-to-treat with multiple imputation for missing data. Cost, quality-adjusted life years (QALYs) from the EQ-5D-5L instrument mapped to EQ5D-3L, and incremental cost-effectiveness ratios (ICERs) were calculated, for within trial period. Results 459 patients were screened and 335 randomised (168 IM; 167 SC); 303(90%) gave 12-month outcome measures. 139(83%) IM patients attended sessions. At 12 months IM significantly increased DAS28-ESR remissions compared to SC (32% vs 18%, p = 0.004) and other remission assessments. IM increased DAS28-ESR low disease activity (48% vs 32%, p = 0.005). Clinically important reductions in HAQ were seen in patients who achieved remission following IM (mean change at 12-months -0.40; 95% confidence intervals -0.57,-0.22), as well as improvements in both fatigue and pain. There was a minimal increase in erosive damage over 12 months in both groups. Serious adverse events (IM = 15 vs SC = 11) and other adverse events (114 IM,151 SC) were similar between groups. The base case ICER was £43,972 (€51,474) with a probability of being cost effective at £30,000/€35,000 of 0.17. The ICER fell to £29,363 (€24,384) after including patients’ personal costs and lost working time with a probability IM is cost-effective of 0.5 at UK willing to pay thresholds. This estimate was based on the historic prices of biologics and the probability is higher when current drug acquisition costs are applied. Conclusion IM by trained nurses in motivational interviewing techniques is clinically effective in moderate established RA, achieving more remission without increasing harm. It also gave clinically important improvement in pain and fatigue. There is a strong case to adopt this approach in routine practice as increasing remission rates may improve long-term outcomes, reduce future biologic prescribing and thereby improve long term cost-effectiveness. Disclosures E. Nikiphorou None.

Real-World Anti-Tumor Necrosis Factor Treatment in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: Cost-Effectiveness Based on Number Needed to Treat to Improve Health Assessment Questionnaire

2009 ◽  
Vol 36 (7) ◽  
pp. 1421-1428 ◽  
Author(s):  
LILLIAN BARRA ◽  
JANET E. POPE ◽  
MICHAEL PAYNE
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Cost Effectiveness ◽  
Health Assessment Questionnaire ◽  
Tumor Necrosis ◽  
Health Assessment ◽  
Number Needed To Treat ◽  
The Mean ◽  
Assessment Questionnaire ◽  
Necrosis Factor

Objective.To determine the effectiveness and cost-effectiveness of anti-tumor necrosis factor (anti-TNF) medications in a real-world environment for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) using the Health Assessment Questionnaire (HAQ).Methods.We created a database of patients with RA, PsA, or AS treated with anti-TNF agents (etanercept, infliximab, or adalimumab) at a large outpatient rheumatology clinic. Patient characteristics, baseline HAQ prior to treatment, subsequent yearly HAQ, and reasons for termination were collected. The cost based on percentage of patients achieving ≥ 0.2 improvement in HAQ (minimal clinically important difference, MCID) was calculated using the 2008 direct cost (Cdn) of the medication.Results.Data were available on 297 patients (206 with RA, 57 PsA, 34 AS). The mean age was 55 years, with 12 years of disease, and the mean baseline HAQ (standard error, SE) was 1.37 (0.04). The changes in HAQ (SE) at Years 1, 2, and 3 were −0.31 (0.04), −0.24 (0.06), and −0.27 (0.07) for annual cost to achieve MCID of $41,636, $42,077, and $42,147, respectively. The number needed to treat (NNT) was 1.94 (RA), 1.88 (PsA), and 2.30 (AS). There were no statistical differences between the diseases studied.Conclusion.We obtained data on the effectiveness and cost-effectiveness of anti-TNF drugs using the HAQ score, which is known to be an excellent predictor of work disability, morbidity, and mortality. HAQ scores decreased with treatment and were sustained throughout the 3–5 years of followup. The NNT of approximately 2 seems favorable and was similar between diseases.

scholarly journals AB0140 A HIGH-CONFIDENCE DEFINITION OF THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS USING A MONTE CARLO SIMULATION APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1097.2-1098
Author(s):  
V. Strand ◽  
S. Cohen ◽  
L. Zhang ◽  
T. Mellors ◽  
A. Jones ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monte Carlo ◽  
Disease Activity ◽  
Health Assessment Questionnaire ◽  
Health Assessment ◽  
High Confidence ◽  
Response Status ◽  
Definition Of ◽  
Fidelity Score ◽  
Assessment Questionnaire

Background:Therapy choice and therapy change depend on the ability to accurately assess patients’ disease activity. The clinical assessments used to evaluate treatment response in rheumatoid arthritis have inherent variability, normally considered as measurement error, intra-observer variability or within subject variability. Each contribute to variability in deriving response status as defined by composite measures such as the ACR or EULAR criteria, particularly when a one-time observed measurement lies near the boundary defining response or non-response. To select an optimal therapeutic strategy in the burgeoning age of precision medicine in rheumatology, achieve the lowest disease activity and maximize long-term health outcomes for each patient, improved treatment response definitions are needed.Objectives:Develop a high-confidence definition of treatment response and non-response in rheumatoid arthritis that exceeds the expected variability of subcomponents in the composite response criteria.Methods:A Monte Carlo simulation approach was used to assess ACR50 and EULAR response outcomes in 100 rheumatoid arthritis patients who had been treated for 6 months with a TNF inhibitor therapy. Monte Carlo simulations were run with 2000 iterations implemented with measurement variability derived for each clinical assessment: tender joint count, swollen joint count, Health Assessment Questionnaire disability index (HAQ-DI), patient pain assessment, patient global assessment, physician global assessment, serum C-reactive protein level (CRP) and disease activity score 28-joint count with CRP.1-3 Each iteration of the Monte Carlo simulation generated one outcome with a value of 0 or 1 indicating non-responder or responder, respectively.Results:A fidelity score, calculated separately for ACR50 and EULAR response, was defined as an aggregated score from 2000 iterations reported as a fraction that ranges from 0 to 1. The fidelity score depicted a spectrum of response covering strong non-responders, inconclusive statuses and strong responders. A fidelity score around 0.5 typified a response status with extreme variability and inconclusive clinical response to treatment. High-fidelity scores were defined as >0.7 or <0.3 for responders and non-responders, respectively, meaning that the simulated clinical response status label among all simulations agreed at least 70% of the time. High-confidence true responders were considered as those patients with high-fidelity outcomes in both ACR50 and EULAR outcomes.Conclusion:A definition of response to treatment should exceed the expected variability of the clinical assessments used in the composite measure of therapeutic response. By defining high-confidence responders and non-responders, the true impact of therapeutic efficacy can be determined, thus forging a path to development of better treatment options and advanced precision medicine tools in rheumatoid arthritis.References:[1]Cheung, P. P., Gossec, L., Mak, A. & March, L. Reliability of joint count assessment in rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum43, 721-729, doi:10.1016/j.semarthrit.2013.11.003 (2014).[2]Uhlig, T., Kvien, T. K. & Pincus, T. Test-retest reliability of disease activity core set measures and indices in rheumatoid arthritis. Ann Rheum Dis68, 972-975, doi:10.1136/ard.2008.097345 (2009).[3]Maska, L., Anderson, J. & Michaud, K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res (Hoboken) 63 Suppl 11, S4-13, doi:10.1002/acr.20620 (2011).Disclosure of Interests:Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Stanley Cohen: None declared, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

scholarly journals THU0106 PREDICTORS OF FLARE IN RHEUMATOID ARTHRITIS PATIENTS WITH LOW DISEASE ACTIVITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 267.1-267
Author(s):  
K. W. Moon
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Analysis ◽  
Observational Study ◽  
Disease Activity ◽  
Health Assessment Questionnaire ◽  
Health Assessment ◽  
Low Disease Activity ◽  
Erythrocyte Sedimentation ◽  
Euroqol 5D ◽  
Assessment Questionnaire

Background:Low disease activity (LDA) in patients with rheumatoid arthritis (RA) are usually recognized as stable state. In according to most guidelines for RA, monotherapy of disease modifying anti-rheumatic drug (DAMRD) was recommended for RA patents with LDA. But some of patients with LDA suffer from flare in their disease course. Until now, we don’t have enough data on factors that can predict flare in RA patients with LDA.Objectives:The aim of this study is to evaluate predictor of flare in RA patient with LDA from long-term (3 year) cohort data.Methods:Korean observational study network for arthritis (KORONA) registry is a nationwide Korean RA specific cohort registry that collecting data annually from 5,376 RA patients in 23 centers across South Korea. We include the data from 1, 801 RA patients with LDA (28 –joint disease activity score (DAS 28) < 3.2 at enrollment) who had consecutive data of DAS28 for 3 years. Flare was defined as an increase in DAS28 compared with baseline of >1.2 or >0.6 if concurrent DAS28 ≥3.2. Cox regression analysis was used to identify baseline predictors of flare.Results:Among 1,801 RA patients, 673 patients (37.4%) experienced flare in 3 years. When we compare the baseline characteristics of both flare and non-flare group, more women and more non-adherent patients for medication were observed in flare group. Flare group had longer disease duration, lower EuroQol 5D score, higher health assessment questionnaire (HAQ) score, and higher erythrocyte sedimentation rate (ESR) than non-flare group at baseline. In multivariate analysis, physician’s VAS, HAQ score, ESR, and poor adherence for medication were significant predictors of flare (Table 1).Table 1.Multivariate analysis of prediction of flare with baseline variablesMeasureHazard ratio95% Confidence IntervalP-valueFemale1.1300.906-1.4090.280Age0.9960.988-1.0050.414Physician’s VAS1.0081.002-1.013<0.01Pain VAS1.0020.998-1.0060.34EQ5D0.9520.534-1.6960.87HAQ1.4071.109-1.786<0.01ESR1.0081.002-1.014<0.01Poor adherence1.2721.047-1.545<0.05VAS: Visual Analogue Scale; EQ5D: EuroQol 5D; HAQ: Health Assessment Questionnaire; ESR: Erythrocyte Sedimentation RateConclusion:RA patient who have risk factors for flare, even though their disease activity was low, require more proactive treatment.References:[1]Bechman K, Tweehuysen L, Garrood T, Scott DL, Cope AP, Galloway JB, et al. Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes. J Rheumatol. 2018;45(11):1515-21.[2]Singh JA, Saag KG, Bridges SL, Jr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.[3]Sung YK, Cho SK, Choi CB, Park SY, Shim J, Ahn JK, et al. Korean Observational Study Network for Arthritis (KORONA): establishment of a prospective multicenter cohort for rheumatoid arthritis in South Korea. Semin Arthritis Rheum. 2012;41(6):745-51.Disclosure of Interests:None declared

scholarly journals Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

2020 ◽  
Vol 24 (2) ◽  
pp. 1-180 ◽  
Author(s):  
Nigel Fleeman ◽  
Rachel Houten ◽  
Adrian Bagust ◽  
Marty Richardson ◽  
Sophie Beale ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cost Effectiveness ◽  
Systematic Reviews ◽  
Observational Studies ◽  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Clinical Effectiveness ◽  
Economic Evaluations ◽  
Base Case ◽  
The Cost

Background Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). Objectives We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. Data sources EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. Review methods We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. Results Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. Limitations We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. Conclusions Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. Study registration This study is registered as PROSPERO CRD42017055516. Funding The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of Different Intra-articular Drug Injections on Wrist and/or Elbow Compromise in Patients With Established Rheumatoid Arthritis

2018 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Zhi Qin Li ◽  
Zhao Hui Zheng ◽  
Lin Xuan Pang ◽  
Jin Ding ◽  
Wang Lei Du ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cost Effectiveness ◽  
Established Rheumatoid Arthritis
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