Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: A cost-effectiveness analysis

Division of Rheumatology, Department of Internal Medicine, University of Geneva, Geneva, Switzerland.
Annals of internal medicine (Impact Factor: 17.81). 11/2009; 151(9):612-21. DOI: 10.1059/0003-4819-151-9-200911030-00006
Source: PubMed


Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined.
To assess the potential cost-effectiveness of major therapeutic strategies for very early RA.
Decision analytic model with probabilistic sensitivity analyses.
Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs.
U.S. adults with very early RA (symptom duration <or=3 months).
Health care provider and societal.
3 management strategies were compared: a symptomatic or "pyramid" strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, and low-dose glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate.
Cost per quality-adjusted life-year (QALY) gained.
By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater.
The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for patients for whom several biologics have failed.
Data on the long-term effect of very early therapeutic interventions on the natural progression in disability and joint erosions are limited. The study considered only tumor necrosis factor inhibitors and not the newer biologics.
According to the most objective measures of RA progression, very early intervention with conventional DMARDs is cost-effective. The cost-effectiveness of very early intervention with biologics remains uncertain.

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Available from: Carlo A Marra, Dec 16, 2014
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    • "Non-steroidal anti-inflammatory drugs and biologics are commonly used to alleviate the symptoms of RA [15]. However, there are severe adverse reactions associated with the prolonged use of these drugs [16]. "
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    ABSTRACT: Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues. The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group. These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.
    BMC Complementary and Alternative Medicine 07/2013; 13(1):186. DOI:10.1186/1472-6882-13-186 · 2.02 Impact Factor
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    • "When the cost of very early intervention was factored in, the cost effectiveness ratio of the early DMARD strategy was $4849 per QALY (95% CI: $0–16,354 per QALY) in comparison with the pyramid strategy, whereas the benefits gained using the early biological strategy came at a substantially increased cost. Very early intervention with conventional DMARDs is cost effective, whereas the cost effectiveness of very early intervention with biological agents remains uncertain [28]. "
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    ABSTRACT: The cost effectiveness of treatments that have changed the "natural history" of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.
    International Journal of Rheumatology 11/2011; 2011(1687-9260):845496. DOI:10.1155/2011/845496
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    • "In summary, our results suggest that the expression levels of VEGF and IL-8 transcripts and proteins are up-regulated in response to poly (I:C), a synthetic TLR3 ligand, through the NF-κB signaling pathway. Angiogenesis is an early and critical event in the pathogenesis in RA, and recent evidence suggests that aggressive treatment during the very early stages of RA can be beneficial, implying the existence of a critical therapeutic window of opportunity [30]. Effective blockade of specific TLR signaling is a potential therapeutic option to prevent progression to joint destruction. "
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    ABSTRACT: Angiogenesis, which is a critical step in the initiation and progression of rheumatoid arthritis (RA), involves pro-angiogenic factors, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). We investigated the role of Toll-like receptor 3 (TLR3) in the regulation of pro-angiogenic factors in RA fibroblast-like synoviocytes (FLS). FLS were isolated from RA synovial tissues and stimulated with the TLR3 ligand, poly (I:C). The levels of VEGF and IL-8 in the culture supernatants were measured using enzyme-linked immunosorbent assays, and the mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction. The expression patterns of VEGF and IL-8 in the RA synovium and osteoarthritis (OA) synovium were compared using immunohistochemistry. The expression levels of TLR3, VEGF, and IL-8 were significantly higher in the RA synovium than in the OA synovium. VEGF and IL-8 production were increased in the culture supernatants of RA FLS stimulated with poly (I:C), and the genes for these proteins were up-regulated at the transcriptional level after poly (I:C) treatment. Treatment with inhibitors of nuclear factor-kappaB (NF-κB), i.e., pyrrolidine dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (I:C) on the production of VEGF and IL-8 in RA FLS. Our results suggest that the activation of TLR3 in RA FLS promotes the production of proangiogenic factors, in a process that is mediated by the NF-κB signaling pathway. Therefore, targeting the TLR3 pathway may be a promising approach to preventing pathologic angiogenesis in RA.
    The Korean Journal of Internal Medicine 12/2010; 25(4):429-35. DOI:10.3904/kjim.2010.25.4.429 · 1.43 Impact Factor
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