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Figure 2, Table 2
(McInnes 2011)
Table 3
(McInnes 2011)
Tayler's Section
Possible early rheumatoid arthritis biomarkers
Describes Biomarkers (increased TC,
LDL-C, nonHDL-C and triglyceride serum levels and reduction in HDL-C levels) that may be used to diagnose RA
(Georgiadis, 2006)
Urine
Kang et al. 2014
Using urine gives higher predictive power for disease activity than conventional serum analysis. Levels of urinary soluble CD14 were abundant in patients with RA and used as new biomarkers.
Elucidation of the pathogenic mechanisms that initiate andperpetuate rheumatoid arthritis offers the promise of progress in each of thesedomains.
(McInnes 2011)
Sustained remission is rarely achieved and requires ongoing pharmacologic therapy
(McInnes 2011)
Reliable predictive biomarkers of prognosis, therapeutic response, and toxicity are lacking
(McInnes 2011)
Molecular remission and the capacity to reestablish immunologic tolerance remain elusive.
(McInnes 2011)
(McInnes 2011)
Amy Vu's Section
Biomarkers in Rheumatoid Arthritis editorial by Hindawi Journals
(Goëb 2014)
A panel of urinary biomarkers were determined to be characteristic of early onset RA with a sensitivity of 88% and specificity of 93%.
(Stalmach 2014.)
ID of 39 peptides that were significantly different in cases of RA versus controls
Cytokine biomarkers and the promise of personalized therapy in rheumatoid arthritis
(Davis 2014)
ability to check cytokine levels throughout treatment as a way of observing disease prognosis
1) Plasma miR-132 test at a cutoff value of 67.8 pmol/l could detect individuals with RA at 83.8% of sensitivity and 80.7% of specificity.
(Murata 2010.)
2) Circulating miRNA-125b is a potential biomarker predicting response to rituximab in rheumatoid arthritis
(Duroux 2013.)
miRNA-125 levels at onset of RA is indicative of effectiveness of treatment with rituximab
Different concentrations of miRNAs found in synovial fluid of RA individuals
Amy Vu's Section
Deleterious process of joint destruction mediated by intracellular signaling pathways involving
(Müller-Ladner 2005)
Cytokine-independent pathways responsible for maintaining basic disease activity
Cytokine-independent pathways appear to be responsible for maintaining basic disease activity that is not affected by currently available therapies.
(Müller-Ladner 2005)
"RA: History, Molecular Mechanisms, and Therapeutic Applications"
(Fishman 2010)
A3AR agonists = proliferation of fibroblast-like synoviocytes
inhibition of pro-inflammatory cytokines
"Mechanism of Disease: the molecular and cellular basis of joint destruction in RA"
(Muller-Ladner, 2005)
Toll-like receptors (TLRs) involved in initial onset of innate immune response of inflammation
"Synovial Fibroblasts: key Players in RA"
(Huber 2006)
IL-15 = proinflammatory cytokine produced by RASF
Positive-feedback loop through activation of T cells which activate more RASF
Agnes Section
cytokine profile at the earliest time points after onset of symptomscould identify novel targets that prevent progression to chronic arthritis.
(Firestein 2005)
Criteria clearly allows earlier diagnosis of RA, although the clinical picture is slightly different on the group level. RA may be falsely diagnosed in some patients with self-limiting disease.
(de Hair 2012)
(Ruffing & Bingham 2012)
(Am J Hum, 2004)
Candidate Genes with SNPs Linked to RA and Their Potential Function in Pathogenesis
Table 1
(McInnes 2011)
No laboratory test will definitively confirm a diagnosis of rheumatoid arthritis.
(Ruffing & Bingham 2012)
Synovial Fluid
Anti CCP antibodies
CRP
ESR
RF
CMP
CBC
Jolene
Clifton, Ruffing. November 28, 2012
In cases of extreme pain, patients can opt for surgical intervention that will prevent further impairment and decrease pain.
Synovectomy, Arthrodesis, Arthroplasty
Biologics are designed to inhibit certain components of the immune system, such as those that are responsible for inflammation. They are one of the only treatment options that slow the progression of RA.
Actemra,Cimzia,Enbrel,Humira,Kineret, Orencia, Remicade, Rituxan, Simponi
Disease Modifying Anti-Rheumatic Drugs (DMARDs) improve symptoms and can change the course of the disease and can improve radiographic outcomes.
Methotrexate, Hydroxychloroquine,Sulfasalazine, Leflunomide, Tumor Necrosis Factor Inhibitor, T Cell Costimulatory Blocking Agents, B cell depleting agents, Interleukin-1 (IL-1) Receptor Antagonist Therapy, Intramuscular Gold
Corticosteroids have both anti-inflammatory and immunoregulatory activity. They can be administered orally, IM, IV and are useful in early stages of the disease.
Prednisone, Methylprenisolone, Medrol
Non Steroidal Anti Inflammatory Drugs reduce acute infection, decrease pain, and improve function. They do not however, change the course of the disease.
Cox-II inhibitors
Celecoxib
Prescribed Drugs
Meloxicam, Etodolac, Nabumeton, Sulindac, Tolementin, Choline Magnesium Salicylate, Diclofenac, Diflusinal, Indomethicin, Ketoprofen, Oxaprozin, Piroxicam
OTCD
Aspirin, Ibuprofen, Naproxen
Sumithra's section
Indirect costs are costs where resources are lost.An average of US$ 37,501 annually.
Economic burden of rheumatoid arthritis: a systematic review.
(N.J.Cooper,2000)
Morality cost- Calculated present value of lost production due to death caused by RA.
Morbidity - Losses due to restriction from illness.
Economic burden of rheumatoid arthritis: a systematic review.
(N.J.Cooper,2000)
Direct costs include medical costs such as treatment,hospital and medication costs. These are worth US$ 5720 annually.
Economic burden of rheumatoid arthritis: a systematic review
(N.J.Cooper, 2000)
\
Cost of diagnosis and laboratory tests
ESR, RF test and X rays- These lab tests cost $25- $30 each on an average. Multiple tests need to be conducted, hence COI (Cost of Illness) rises in the long run.
The cost of rheumatoid arthritis.
( E.McINTOSH, 1996)
Hospital visits- these account for about US$1855 to US$4944
Economic burden of rheumatoid arthritis: a systematic review.
(N.J.Cooper)
Treatment cost
Genetically engineered drugs on an average cost about $1000-$3000 per month depending on the stage of RA.
The cost of rheumatoid arthritis.
(E.McINTOSH, 1996)
TNF blocking agents though comparatively higher in cost.
TNF blocking agents (Etanercept, Infliximab)though comparatively higher in cost, is both efficient and cost effective when standard dosing regimens are used.
Cost Effectiveness analysis of Disease-Modifying Anti-rheumatic Drugs in rheumatoid arthritis. A systematic Review Literature.
(Maurizio Benucci, 2011)
Cost of using DMARDs (CyA, Methotrexate, sulphasalazine)
Usage of DMARDs have been proved to be cost effective at the time of disease onset.
Cost Effectiveness analysis of Disease-Modifying Anti-rheumatic Drugs in rheumatoid arthritis. A systematic Review Literature.
(Maurizio Benucci, 2011)
Steve's Section
Reproductive Hormone
Oral contraceptives, Hormone replace therapy, live birth history, menstrual history (Barrett, 1999)
Smoking
Strongest and consistent data. Modest to moderate risk (1.3-2.4x) (Carlens, 2010)
Growing up under drug-alcohol addicted parents
Fuller-Thomson, 2014
Infection by P. gingivalis
Synovial fluid of patients contain oral anaerobic bacterial antibodies associated with P. gingivalis. Other indirect studies with Mycoplasma, EBV, and rubella. (Hitchon, 2010)
Women are affected 3x more than men
RA in sex differences diminish as age increases. Danish study - rate higher for women with 1 childbirth than 2 or 3. Reduced immune adaptability may exist for women predisposed to RA (Ahlmen, 2010)
Relatives have 2-3x increase chance of RA
Increases with age 35-50
(Temprano, 2014)
60% of cases of RA in US carry shared epitope of leukocyte antigen HLA-DR4 cluster. (Barton, 2009)
Signs and symptoms of Rheumatoid Arthritis
(Source: 2014, http://www.niams.nih.gov/Health_Info/Rheumatic_Disease/)
Morning Stiffness
Joint pain
Loss of range of motion
Difficulty Breathing/Chest pain
Tendency to bruise
bone fracture
high fever/signs of infection
Red inflamed eyes/discharge from eyes
Numbness/tingling
Nodules under skin
Anthony's Section
Worldwide distribution
More prevalent in some subsets of Native Americans
Also in incidence section
(Firestein 2003)
Depicts worldwide incidence of Rheumatoid Arthritis as well as costs
(Kvien, 2004)
UK
Incidence of Rheumatoid Arthritis in the UK
(Symmons, 1994)
Females
27-30/100,000
Males
10-11/100,000
Worldwide distribution 1-2%
Prevalence increases with age
5% in women over 55
Percentages vary for age groups and genders. Refer to paper for other percentages with age and gender.
higher in pregnant women
2-3 times higher in women than men
(Ahlmen, 2010)
incidence of Americans based on study from Olmsted County, Minnesota (Myasoedova,2010)
Male
145/100,000
Female
321/100,000
