2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease???Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis

University of Alabama at Birmingham.510 20th Street South, Birmingham, AL 35294, USA.
Arthritis care & research 05/2012; 64(5):625-39. DOI: 10.1002/acr.21641
Source: PubMed


Figure 2. 2012 American College of Rheumatology (ACR) recommendations update for the treatment of established rheumatoid arthritis (RA), defined as a disease duration ≥6 months or meeting the 1987 ACR classification criteria. Depending on a patient's current medication regimen, the management algorithm may begin at an appropriate rectangle in the figure, rather than only at the top of the figure. Disease-modifying antirheumatic drugs (DMARDs) include hydroxychloroquine (HCQ), leflunomide (LEF), methotrexate (MTX), minocycline, and sulfasalazine (therapies are listed alphabetically; azathioprine and cyclosporine were considered but not included). DMARD monotherapy refers to treatment in most instances with HCQ, LEF, MTX, or sulfasalazine; in few instances, where appropriate, minocycline may also be used. Anti–tumor necrosis factor (anti-TNF) biologics include adalimumab, certolizumab pegol, etanercept, infliximab, and golimumab. Non-TNF biologics include abatacept, rituximab, or tocilizumab (therapies are listed alphabetically). For the level of evidence supporting each recommendation, please see Supplementary Appendix 7 (available in the online version of this article at* Definitions of disease activity are discussed in Tables 2 and 3 and Supplementary Appendix 4 (available in the online version of this article at and were categorized as low, moderate, or high.† Features of poor prognosis included the presence of 1 or more of the following: functional limitation (e.g., Health Assessment Questionnaire score or similar valid tools), extraarticular disease (e.g., presence of rheumatoid nodules, RA vasculitis, Felty's syndrome), positive rheumatoid factor or anti–cyclic citrullinated peptide antibodies (33–37), and bony erosions by radiograph (38).‡ Combination DMARD therapy with 2 DMARDs, which is most commonly MTX based, with few exceptions (e.g., MTX + HCQ, MTX + LEF, MTX + sulfasalazine, sulfasalazine + HCQ), and triple therapy (MTX + HCQ + sulfasalazine).§ Reassess after 3 months and proceed with escalating therapy if moderate or high disease activity in all instances except after treatment with a non-TNF biologic (rectangle D), where reassessment is recommended at 6 months due to a longer anticipated time for peak effect.¶ LEF can be added in patients with low disease activity after 3–6 months of minocycline, HCQ, MTX, or sulfasalazine.# If after 3 months of intensified DMARD combination therapy or after a second DMARD has failed, the option is to add or switch to an anti-TNF biologic.** Serious adverse events were defined per the US Food and Drug Administration (FDA; see below); all other adverse events were considered nonserious adverse events.†† Reassessment after treatment with a non-TNF biologic is recommended at 6 months due to anticipation that a longer time to peak effect is needed for non-TNF compared to anti-TNF biologics.‡‡ Any adverse event was defined as per the US FDA as any undesirable experience associated with the use of a medical product in a patient. The FDA definition of serious adverse event includes death, life-threatening event, initial or prolonged hospitalization, disability, congenital anomaly, or an adverse event requiring intervention to prevent permanent impairment or damage.Download figure to PowerPoint

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Available from: Jasvinder A Singh, Jul 15, 2015
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    • "JIA is the most common chronic rheumatic illness in children and it is responsible for short and long-term disability [2]. In the recent years an increased number of disease-modifying anti-rheumatic drugs (DMARDs) have been developed for treatment of JIA, but methotrexate (MTX) is still the most common second line therapeutic agent used in treatment of JIA worldwide, either as monotherapy or in combination with biologic agents [3-10]. However, there is variation in the clinical response to MTX among the patients, while there does not appear to be any advantages related to efficacy or safety with either the oral or parenteral method of administration although it is believed by many pediatric rheumatologist that for severe JIA parenteral application may be an advantage [11]. "
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    ABSTRACT: The response to methotrexate so far is unpredictable in patients with juvenile idiopathic arthritis. Thus such predictors have to be determined in a large patient cohort. Demographic, clinical, articular and laboratory variables of patients newly treated with methotrexate were analysed by bivariate and logistic regression analysis to identify predictors of response to methotrexate. Minimal response was defined by the American College of Rheumatology pediatric (PedACR) 30 and strong response by the PedACR 70 criteria. The patient population consisted of 731 patients. At month 3, 77.4% and at month 12 83.1% of patients were responders according to the PedACR 30 criteria, while 43.1% and 65.9% of patients had a PedACR 70 response at month 3 and at month 12. Thus minimal response was frequently already reached at month 3 while strong response to MTX treatment took usually longer to achieve. In multivariate analysis the number of tender joints (p = 0.002), active joints (p < 0.001), concomitant use of NSAID (p = 0.027) and the parents evaluation of overall well-being (p < 0.001) were significant baseline parameters for minimal response at month 3, while at month 12 the determinants for reaching PedACR 70 were a disease duration < 1 year (p =0.001), a lower number of tender (p <0.001) but a higher number of active joints (p <0.001), a higher score of the parent’s evaluation of child’s pain (p =0.029), and the presence of morning stiffness (p =0.014). Baseline parameters for minimal response after 3 months of treatment and strong response after 12 months of treatment could be identified. Beside parameters defining activity and severity of disease, the disease duration and the concomitant use of NSAID were influencing factors. Overall the model of prediction could support physicians in making treatment decisions.
    Full-text · Article · Aug 2014 · Pediatric Rheumatology
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    • "Anti-tumor necrosis factor alpha (TNFα) is often used in patients with rheumatic disease who do not respond to conventional treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroid, or disease modifying anti-rheumatic drugs (DMARDs) (1, 2). Dramatic improvements have been shown in clinical symptoms and signs in patients with ankylosing spondylitis (AS) receiving anti-TNFα. "
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    ABSTRACT: We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFα). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFα and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFα, including type and treatment duration. The median duration of anti-TNFα was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFα in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFα. Graphical Abstract
    Full-text · Article · Aug 2014 · Journal of Korean Medical Science
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    • "Since more than two decades, low dose methotrexate (MTX, 5-25 mg/weekly) has been established as first-line therapeutic agent [7] and has thus been widely used drug in RA therapy [8]. Currently, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have recommended even higher dosages [9,10]. Previous to low dose therapy in RA, MTX was used in oncology at higher dose as antineoplastic agent [11]. "
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    ABSTRACT: Background With socio-economic changes, dentists and maxillofacial surgeons are more and more faced with medically compromised patients. Especially, the admission of antirheumatic drugs has increased remarkably. So dentists and maxillofacial surgeons should be aware of related adverse reactions that affect the craniofacial region. To identify possible cellular effects of disease modifying antirheumatic drugs (DMARDs) we investigated the influence of methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs). Methods HUVECs were incubated with various concentrations of MTX, corresponding to serum concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on cell proliferation, differentiation as well as mitochondrial activity was measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay. Results All samples incubated with MTX (1-1000 nM) showed significantly decreased cell viability when compared to controls. Cells were less proliferating, but did not lose their ability to synthesize endothelial proteins. A slight dose dependency of inhibiting effects was demonstrated. The observed differences between control and sample groups were rising with longer duration. Conclusion Because of the crucial role of endothelial cells and their precursor cells in wound healing, a negative influence of MTX on oral health has to be supposed, correlating to clinical observations of adverse reactions in the oral cavity, such as ulcerative or erosive lesions.
    Full-text · Article · May 2014 · Head & Face Medicine
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