Терапия

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Updated Guidelines on Cardiopulmonary Resuscitation: A Report from SHM 2006
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[Наталья П.]

Health Technology Assessment 2006
Центр оценки медицинских технологий

Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation

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[Наталья П.]

Журнал "Оценка медицинских технологий"
полный текст pdf
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Health Technol Assess. 2006 Nov;10(42):1-248.

A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, Fry-Smith A, Burls A.

West Midlands Health Technology Assessment Collaboration (WMHTAC), Department of Public Health and Epidemiology, University of Birmingham, UK.

OBJECTIVES: This report reviews the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab, agents that inhibit tumour necrosis factor-alpha (TNF-alpha), when used in the treatment of rheumatoid arthritis (RA) in adults.
DATA SOURCES: Electronic databases were searched up to February 2005.
REVIEW METHODS: Systematic reviews of the literature on effectiveness and cost-effectiveness were undertaken and industry submissions to the National Institute for Health and Clinical Excellence (NICE) were reviewed. Meta-analyses of effectiveness data were also undertaken for each agent. The Birmingham Rheumatoid Arthritis Model (BRAM), a simulation model, was further developed and used to produce an incremental cost-effectiveness analysis.
RESULTS: Twenty-nine randomised controlled trials (RCTs), most of high quality, were included. The only head-to-head comparisons were against methotrexate. For patients with short disease duration (</=3 years) who were naive to methotrexate, adalimumab was marginally less and etanercept was marginally more effective than methotrexate in reducing symptoms of RA. Etanercept was better tolerated than methotrexate. Both adalimumab and etanercept were more effective than methotrexate in slowing radiographic joint damage. Etanercept was also marginally more effective and better tolerated than methotrexate in patients with longer disease durations who had not failed methotrexate treatment. Infliximab is only licensed for use with methotrexate. All three agents, either alone (where so licensed) or in combination with ongoing disease-modifying antirheumatic drugs (DMARDs), were effective in reducing the symptoms and signs of RA in patients with established disease. At the licensed dose, the numbers needed to treat (NNTs) (95% CI) required to produce an American College for Rheumatology (ACR) response compared with placebo were: ACR20: adalimumab 3.6 (3.1 to 4.2), etanercept 2.1 (1.9 to 2.4), infliximab 3.2 (2.7 to 4.0); ACR50: adalimumab 4.2 (3.7 to 5.0), etanercept 3.1 (2.7 to 3.6), infliximab 5.0 (3.8 to 6.7); and ACR70: adalimumab 7.7 (5.9 to 11.1), etanercept 7.7 (6.3 to 10.0), infliximab 11.1 (7.7 to 20.0). In patients who were naive to methotrexate, or who had not previously failed methotrexate treatment, a TNF inhibitor combined with methotrexate was significantly more effective than methotrexate alone. Infliximab combined with methotrexate had an increased risk of serious infections. All ten published economic evaluations met standard criteria for quality, but the incremental cost-effectiveness ratios (ICERs) ranged from being within established thresholds to being very high because of varying assumptions and parameters. All three sponsors who submitted economic models made assumptions favourable to their product. BRAM incorporates improvements in quality of life and mortality, but assumes no effect of TNF inhibitors on joint replacement. For use in accordance with current NICE guidance as the third DMARD in a sequence of DMARDs, the base-case ICER was around pound30,000 per quality-adjusted life-year (QALY) in early RA and pound50,000 per QALY in late RA. Sensitivity analyses showed that the results were sensitive to the estimates of Health Assessment Questionnaire (HAQ) progression while on TNF inhibitors and the effectiveness of DMARDs, but not to changes in mortality ratios per unit HAQ. TNF inhibitors are most cost-effective when used last. The ICER for etanercept used last is pound24,000 per QALY, substantially lower than for adalimumab ( pound30,000 per QALY) or infliximab ( pound38,000 per QALY). First line use as monotherapy generates ICERs around pound50,000 per QALY for adalimumab and etanercept. Using the combination of methotrexate and a TNF inhibitor as first line treatment generates much higher ICERs, as it precludes subsequent use of methotrexate, which is cheap. The ICERs for sequential use are of the same order as using the TNF inhibitor alone.
CONCLUSIONS: Adalimumab, etanercept and infliximab are effective treatments compared with placebo for RA patients who are not well controlled by conventional DMARDs, improving control of symptoms, improving physical function, and slowing radiographic changes in joints. The combination of a TNF inhibitor with methotrexate was more effective than methotrexate alone in early RA, although the clinical relevance of this additional benefit is yet to be established, particularly in view of the well-established effectiveness of MTX alone. An increased risk of serious infection cannot be ruled out for the combination of methotrexate with adalimumab or infliximab. The results of the economic evaluation based on BRAM are consistent with the observations from the review of clinical effectiveness, including the ranking of treatments. TNF inhibitors are most cost-effective when used as last active therapy. In this analysis, other things being equal, etanercept may be the TNF inhibitor of choice, although this may also depend on patient preference as to route of administration. The next most cost-effective use of TNF inhibitors is third line, as recommended in the 2002 NICE guidance. Direct comparative RCTs of TNF inhibitors against each other and against other DMARDs, and sequential use in patients who have failed a previous TNF inhibitor, are needed. Longer term studies of the quality of life in patients with RA and the impact of DMARDs on this are needed, as are longer studies that directly assess effects on joint replacement, other morbidity and mortality.

[Наталья П.]

Doctorsforadults.com is brought to you by the American College of Physicians, the world's largest internal medicine society.


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[Наталья П.]

Rheumatol Int. 2007 May 16; [Epub ahead of print] Related Articles, LinkOut


Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis.

Emery P, Gabay C, Kraan M, Gomez-Reino J.

Academic Unit of Musculoskeletal Disease, Leeds University, Chapel Town Road, Leeds, LS7 4S, UK, [Ссылки доступны только зарегистрированным пользователям ].

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease characterised by inflammation resulting in structural joint damage and functional disability\. Tumour necrosis factor-alpha (TNFalpha) is a pivotal mediator and driver of inflammation in RA\. Inflammation is closely related to the production of C-reactive protein (CRP), and a close correlation exists between serum CRP and TNFalpha levels\. CRP levels are therefore a convenient, objective biomarker of disease activity\. CRP correlates closely with changes in inflammation/disease activity, radiological damage and progression and functional disability\. Identification of TNFalpha as a driver of RA progression has led to the introduction of TNFalpha-blocking agents and, subsequently, improvement of disease management\. TNFalpha-blocking agents provide rapid, profound and sustained suppression of disease activity in correspondence with a marked reduction in CRP levels\. A reduction in CRP level correlates closely with the positive clinical response to TNFalpha-blocking therapy\. Thus, CRP levels can be used to predict, assess and monitor response to treatment with TNFalpha-blocking agents, and may be helpful in determining the optimal TNFalpha-blocker dosage\. Given the close correlation between inflammation and disease progression and the relation between inflammation and CRP, the latter, if used effectively in clinical practice, may be means to identify patients likely to progress rapidly and who require intensive anti-TNFalpha therapy\. The purpose of this review is to identify how CRP levels may be useful for monitoring the effect of therapy on halting disease progression and why monitoring CRP levels at baseline and after treatment should become a routine part of clinical practice.

PMID: 17505829 [PubMed - as supplied by publisher]


Ann Rheum Dis. 2007 May 15; [Epub ahead of print] Related Articles, LinkOut


EULAR recommendations for the management of Systemic Lupus Erytematosus (SLE) Report of a Task Force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)*

Bertsias GK, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, Dostal C, Font J, Gilboe IM, Houssiau F, Huizinga T, Isenberg D, Kallenberg CG, Khamashta M, Piette JC, Schneider M, Smolen J, Sturfelt G, Tincani A, van Vollenhoven R, Gordon C, Boumpas DT.

Internal Medicine, and Rheumatology, Clinical Immunology and Allergy, University of Crete, Greece.

OBJECTIVE: SLE is a complex disease with variable presentations, course and prognosis\. We sought to develop evidenced-based recommendations addressing the major issues in the management of SLE\. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist\. Key questions for the management of SLE were compiled using the Delphi technique\. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring, and treatment of SLE\. For neuropsychiatric, pregnancy, and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms\. Evidence was categorized based on sample size and type of design and the categories of available evidence were identified for each recommendation\. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists\. RESULTS: Twelve questions were generated regarding the prognosis, diagnosis, monitoring, and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome, and lupus nephritis\. The evidence to support each proposition was evaluated and scored\. After discussion and votes, the final recommendations were presented using brief statements\. The average agreement among experts was 8.8 out of 10\. CONCLUSION: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

PMID: 17504841 [PubMed - as supplied by publisher]

[Наталья П.]

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Summaries and commentary of general medical journal articles covering topics such as asthma, diabetes, arthritis, and obesity.

[Наталья П.]

Oonline teaching resource authored by clinician-educators in our internal medicine residency program.
It’s called ProfessorEBM.com,
and it consists of about 80 teaching modules on common inpatient medicine topics. The modules consist of sample cases, questions, suggested answers, and evidence-based summaries of key reference articles, as well as links to articles and abstracts. They are designed to “teach the teacher” on how to review the evidence on common inpatient medicine problems.

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