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Fulltext Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis

Dalila AS, Mohd Said MS, Shaharir SS, Asrul AW, Low SF, Shamsul AS, et al.

Kaohsiung J. Med. Sci., 2014 Jul;30(7):337-42.
PMID: 24924839 DOI: 10.1016/j.kjms.2014.02.010

The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire-Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.

Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
Biomechanical analysis of rheumatoid arthritis of the wrist joint

Bajuri MN, Kadir MR, Amin IM, Ochsner A

Proc Inst Mech Eng H, 2012 Jul;226(7):510-20.
PMID: 22913098 DOI: 10.1177/0954411912445846

The wrist is the most complex joint for virtual three-dimensional simulations, and the complexity is even more pronounced when dealing with skeletal disorders of the joint such, as rheumatoid arthritis (RA). In order to analyse the biomechanical difference between healthy and diseased joints, three-dimensional models of these two wrist conditions were developed from computed tomography images. These images consist of eight carpal bones, five metacarpal bones, the distal radius and ulna. The cartilages were developed based on the shape of the available articulations and ligaments were simulated via mechanical links. The RA model was developed accurately by simulating all ten common criteria of the disease related to the wrist. Results from the finite element (FE) analyses showed that the RA model produced three times higher contact pressure at the articulations compared to the healthy model. Normal physiological load transfer also changed from predominantly through the radial side to an increased load transfer approximately 5% towards the ulnar. Based on an extensive literature search, this is the first ever reported work that simulates the pathological conditions of the rheumatoid arthritis of the wrist joint.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
The expression of rheumatoid arthritis in Malaysian and British patients: a comparative study

Veerapen K, Mangat G, Watt I, Dieppe P

Br J Rheumatol, 1993 Jul;32(7):541-5.
PMID: 8339122

Seventy consecutive patients with definite or classical RA attending a University Hospital Rheumatology Clinic in Malaysia, were compared with an age, sex, disease duration matched group of RA patients seen in a British University Hospital. There were no differences in measures of disease activity, overall functional status or serological status in the two groups. However significant differences were seen in both the articular and extra-articular manifestations of the disease in the two countries. British patients had more severe disease in the feet, and a higher prevalence of nodules, vasculitis and pulmonary fibrosis. The Malaysian population had fewer erosions, more frequent involvement of the wrists and cervical spine, and a much higher incidence of secondary sicca syndrome. Radiographic changes were generally milder in Malaysian patients. Possible reasons for these differences in the expression of RA in the two countries are discussed.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation

Sharma JN

Agents Actions Suppl., 1992;38 ( Pt 3):343-61.
PMID: 1334358

Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
Development and validation of a novel rheumatoid arthritis knowledge assessment scale in Pakistani patients with rheumatoid arthritis

Naqvi AA, Hassali MA, Iffat W, Zia M, Fatima M, Shakeel S, et al.

Int J Rheum Dis, 2019 Nov;22(11):2031-2044.
PMID: 31595667 DOI: 10.1111/1756-185X.13721

AIM: Rheumatoid arthritis (RA) is a chronic progressive disabling disease that mainly affects joints. Studies documenting Pakistani patients' knowledge regarding RA disease are lacking and there is a need for such endeavor. The purpose of this study was to develop and validate a novel research tool to document patient knowledge about RA disease.
METHODS: A novel research instrument known as the rheumatoid arthritis knowledge assessment scale (RAKAS) which consisted of 13 items, was formulated by a rheumatology panel and used for this study. This study was conducted in rheumatology clinics of three tertiary care hospitals in Karachi, Pakistan. The study was conducted in March-April 2018. Patients were recruited using a randomized computer-generated list of appointments. Sample size was calculated based on item-to-respondent ratio of 1:15. The validities, factor structure, sensitivity, reliability and internal consistency of RAKAS were assessed. The study was approved by the institutional Ethics Committee.
RESULTS: A total of 263 patients responded to the study. Content validity was 0.93 and response rate was 89.6%. Factor analysis revealed a 3-factor structure. Fit indices, namely normed fit index (NFI), Tucker Lewis index (TLI), comparative fit index (CFI) and root mean square of error approximation (RMSEA) were calculated with satisfactory results, that is, NFI, TLI and CFI > 0.9, and RMSEA 19 and difficulty index <0.95. Sensitivity and specificity of RAKAS were above 90%. The tool established construct and known group validities.
CONCLUSION: A novel tool to document disease knowledge in patients with RA was formulated and validated.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
Mechanical and functional assessment of the wrist affected by rheumatoid arthritis: A finite element analysis

Bajuri MN, Kadir MR, Raman MM, Kamarul T

Med Eng Phys, 2012 Nov;34(9):1294-302.
PMID: 22277308 DOI: 10.1016/j.medengphy.2011.12.020

Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
Fulltext Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis

Noh ASM, Chuan TD, Khir NAM, Zin AAM, Ghazali AK, Long I, et al.

PLoS One, 2021;16(12):e0260423.
PMID: 34879087 DOI: 10.1371/journal.pone.0260423

Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
Biomechanical analysis of the wrist arthroplasty in rheumatoid arthritis: a finite element analysis

Bajuri MN, Abdul Kadir MR, Murali MR, Kamarul T

Med Biol Eng Comput, 2013 Feb;51(1-2):175-86.
PMID: 23124814 DOI: 10.1007/s11517-012-0982-9

The total replacement of wrists affected by rheumatoid arthritis (RA) has had mixed outcomes in terms of failure rates. This study was therefore conducted to analyse the biomechanics of wrist arthroplasty using recently reported implants that have shown encouraging results with the aim of providing some insights for the future development of wrist implants. A model of a healthy wrist was developed using computed tomography images from a healthy volunteer. An RA model was simulated based on all ten general characteristics of the disease. The ReMotion ™ total wrist system was then modelled to simulate total wrist arthroplasty (TWA). Finite element analysis was performed with loads simulating the static hand grip action. The results show that the RA model produced distorted patterns of stress distribution with tenfold higher contact pressure than the healthy model. For the TWA model, contact pressure was found to be approximately fivefold lower than the RA model. Compared to the healthy model, significant improvements were observed for the TWA model with minor variations in the stress distribution. In conclusion, the modelled TWA reduced contact pressure between bones but did not restore the stress distribution to the normal healthy condition.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
A cross-sectional study of diastolic dysfunction in rheumatoid arthritis and its association with disease activity

Abdul Muizz AM, Mohd Shahrir MS, Sazliyana S, Oteh M, Shamsul AS, Hussein H

Int J Rheum Dis, 2011 Feb;14(1):18-30.
PMID: 21303478 DOI: 10.1111/j.1756-185X.2010.01593.x

AIMS: The aim of this study was to evaluate the left ventricular (LV) diastolic dysfunction in rheumatoid arthritis (RA) patients without clinically evident cardiovascular manifestations and to estimate whether there is any correlation between RA disease severity and disability and LV diastolic dysfunction.
METHODS: The study was a cross-sectional study involving 53 patients (47 female and 6 male) with RA without clinically evident heart disease and 53 healthy subjects (47 female and 6 male) who served as a control group. Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects.
RESULTS: Of 17 cardiac parameters assessed, only two were abnormal. None of the specific cardiac diastolic dysfunction parameters were significantly different in RA patients compared to the control group. There was no significant correlation between diastolic function values in RA patients and value of Disease Activity Score 28 (DAS-28) and value of Health Assessment Questionnaires Disability Index (HAQDI). Atrial (A) wave velocity was greater in RA patients compared to the control group (0.71 [0.58-0.83] vs. 0.61 [0.51-0.71]; P < 0.04). However, interventricular relaxation time (IVRT) ([73.08 ± 9.92 vs. 70.74 ± 9.02], P = 0.207), lower E/A ratio (1.27 [1.02-1.56] vs. 1.42 [1.20-1.68], P = 0.102), diastolic dysfunction parameters according to Redfield Classification (25 [47.2%] vs. 27 [50.9%] P = 0.56), diastolic dysfunction using E/A (P = 0.321) and tissue doppler imaging (E/E') (P = 0.148) were not different.
CONCLUSION: Prevalence of diastolic dysfunction in the rheumatoid arthritis group (47.2%) was not different from controls (50.9%). LV diastolic function had no significant correlation with RA disease severity and duration of disease.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
The pattern and clinical manifestations of rheumatoid arthritis in Sarawak General Hospital

Teh CL, Wong JS

Clin Rheumatol, 2008 Nov;27(11):1437-40.
PMID: 18773254 DOI: 10.1007/s10067-008-0945-6

The aim of our study is to describe the pattern, clinical features, treatment regimes, and disease activity among the patients treated for rheumatoid arthritis (RA) in the Sarawak General Hospital. We performed a cross-sectional study of all patients with a diagnosis of RA who received treatment at the General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital over a 1-year period from 1st June 2006 to 31st May 2007. Demographic data, clinical features, and disease activity of all 154 patients were collected for statistical analysis. Rheumatoid arthritis afflicts all the major racial groups in Sarawak including the native population. Our patients have a mean disease duration of 5.4 years (SD 5.69) and a mean duration of delay in diagnosis RA and initiation of disease-modifying antirheumatic drug (DMARD) treatment of 42.9 months (SD 60.1). They have a low rate of interstitial lung disease (6.5%) and rheumatoid nodules (4.5%). Rheumatoid factor was positive in 65.5% of our patients. They have a mean Disease Activity Score (DAS) 28 score of 4.28 (SD 1.33). Only 12.5% of our patients are in remission with DAS 28 < 2.6 and 30.9% of our patients are having high disease activity with DAS 28 > 5.1. Despite the high usage of DMARDs in Sarawak (>80%), our patients have severe disease with high disease activity indices. This is most likely due to delay in diagnosis and initiating DMARDs in RA patients in Sarawak.

Study site: General Medical Clinic and the Rheumatology Clinic in Sarawak General Hospital

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
Fulltext Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in assessment of anaemia in rheumatoid arthritis

Pavai S, Jayaranee S, Sargunan S

Med J Malaysia, 2007 Oct;62(4):303-7.
PMID: 18551934

Anaemia of chronic disease (ACD) is a frequent complication of rheumatoid arthritis (RA). A diagnostic difficulty in RA is the distinction between iron deficiency anaemia (IDA) and ACD. The aim of our study was to evaluate the usefulness of serum soluble transferrin receptor (sTfR) and sTfR/log ferritin (TfR-F) index to diagnose iron deficiency in RA patients with anaemia. Routine laboratory indices of anaemia and sTfR were measured in 20 healthy persons to form the control group, 30 patients with iron deficiency anaemia and 28 RA patients with anaemia. Serum sTfR levels were significantly elevated above the cut-off value in patients with IDA and those in the iron depleted RA subgroup (ferritin < 60 microg/L) compared with those in the control and iron repleted RA subgroup (ferritin > 60 microg/L). The same was observed for TfR-F index. However, five patients in the iron repleted RA sub group had an elevated sTfR level, of which two had increased TfR-F index. Serum sTfR correlated well with the markers of anaemia and not with ESR. Ferritin had no correlation with markers of anaemia but correlated well with ESR. Measurement of sTfR and TfR-F index are good indicators of iron deficiency in RA patients with anaemia. To be cost effective, sTfR can be estimated in RA patients with anaemia when the ferritin level is more than 60 microg/L.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
The effect of disease activity on fat-free mass and resting energy expenditure in patients with rheumatoid arthritis versus noninflammatory arthropathies/soft tissue rheumatism

Arshad A, Rashid R, Benjamin K

Mod Rheumatol, 2007;17(6):470-5.
PMID: 18084698 DOI: 10.1007/s10165-007-0628-1

Rheumatoid arthritis (RA) is a chronic joint disease of undetermined cause that is associated with significant disability. Low-grade fever, anemia, and weight loss are recognized extra-articular features associated with increased disease activity. Weight loss and cachexia are well-established features of RA. The mechanism behind weight loss in RA is not known and may be multifactorial. Reduced energy intake and hypermetabolism are the major two factors frequently implicated in the etiology of RA cachexia. One would expect the effect of the above two factors to be highest during increased disease activity and lowest during remission. The purpose of this study was: (a) to establish whether in RA patients changes in body composition mirror changes in disease activity, (b) to investigate the relation between the energy expenditures and weight loss, (c) to examine the dietary energy intake and its role in weight loss in RA patients, and (d) to investigate the relation between the cytokine interleukin (IL)-6 and other variables including resting energy expenditure (REE), body composition, and acute phase reactants. Fourteen patients with RA were age-, sex-, and race-matched with 14 controls from patients with noninflammatory diseases/soft tissue rheumatism. The measurements included the following: disease activity assessment, anthropometric measurements, indirect calorimetry, and measurements of dietary intake. Blood was collected to measure the acute-phase reactants and IL-6 levels. We demonstrated that loss of fat-free mass (FFM) might accelerate during times of increased disease activity and is only partially restored during periods of reduced disease activity. This probably means that the extent of cachexia in RA patients is determined by the frequency and intensity of disease activity (flare) for a given disease duration. Hypermetabolism with increased REE was more evident during increased disease activity. Hypermetabolism in the face of increased energy intake continued to cause loss of the FFM. Interleukin-6 correlates with increased REE and erythrocyte sedimentation rate. There was no direct association between IL-6 level and low FFM. We conclude that loss of FFM is common in RA, cytokine production in RA is associated with altered energy metabolism, and preservation of FFM is important in maintaining good quality of life in patients with RA.
Study site: Rheumatology clinic, Putra Specialist Centre, Kedah

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
Fulltext Rheumatoid arthritis serotype and synthetic disease-modifying anti-rheumatic drugs in patients with periodontitis: A case-control study

Nik-Azis NM, Mohd N, Mohd Fadzilah F, Mohamed Haflah NH, Mohamed Said MS, Baharin B

PLoS One, 2021;16(6):e0252859.
PMID: 34153036 DOI: 10.1371/journal.pone.0252859

Patients with rheumatoid arthritis (RA) experience a higher prevalence of periodontitis. This study aimed to examine the variation of periodontitis experienced with different serotypes suffered by RA patients and to examine the relationship between the different medications taken for RA that may influence this relationship. Two hundred and sixty RA and control participants underwent standardized periodontal examinations. Medical, serological and radiological (Sharp/van der Heijde) records were assessed. Functional status was assessed using the administered Health Assessment Questionnaire. Moreover, disease parameters, including disease activity (DAS28-ESR) and anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) seropositivity were evaluated. Periodontitis was higher in RA (71.54%) compared with controls (54.62%). The stage of periodontitis experienced by ACPA-positive participants were higher than APCA-negative participants. The probing pocket depth and recession experienced by RF-positive participants were higher than those who were RF-negative. RA participants on methotrexate had lower clinical attachment loss and lower periodontal probing depth compared with participants on a combination methotrexate and other disease-modifying antirheumatic drugs. Participants taking corticosteroids had lower gingival index scores. The association between seropositivity and the type of medications taken with periodontal health parameters in this group of patients suggests that both seropositivity and medications taken are important modifiers in the relationship between periodontitis and RA.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology*
Fatigue and associated factors in a multi-ethnic cohort of rheumatoid arthritis patients

Lee HJ, Pok LSL, Ng CM, Yahya F, Sockalingam S, Tee YC, et al.

Int J Rheum Dis, 2020 Aug;23(8):1088-1093.
PMID: 32597545 DOI: 10.1111/1756-185X.13897

INTRODUCTION: Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life.
OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.
METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).
RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology
A clinical update and global economic burden of rheumatoid arthritis

Fazal SA, Khan M, Nishi SE, Alam F, Zarin N, Bari MT, et al.

Endocr Metab Immune Disord Drug Targets, 2018 Feb 13;18(2):98-109.
PMID: 29141572 DOI: 10.2174/1871530317666171114122417

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is a predominant inflammatory autoimmune disorder. The incidence and prevalence of RA is increasing with considerable morbidity and mortality worldwide. The pathophysiology of RA has become clearer due to many significant research outputs during the last two decades. Many inflammatory cytokines involved in RA pathophysiology and the presence of autoantibodies are being used as potential biomarkers via the use of effective diagnostic techniques for the early diagnosis of RA. Currently, several disease-modifying anti-rheumatic drugs are being prescribed targeting RA pathophysiology, which have shown significant contributions in improving the disease outcomes.

DISCUSSION: Even though innovations in treatment strategies and monitoring are helping the patients to achieve early and sustained clinical and radiographic remission, the high cost of drugs and limited health care budgets are restricting the easy access of RA treatment. Both direct and indirect high cost of treatment are creating economic burden for the patients and affecting their quality of life.

CONCLUSION: The aim of this review is to describe the updated concept of RA pathophysiology and highlight current diagnostic tools used for the early detection as well as prognosis - targeting several biomarkers of RA. Additionally, we explored the updated treatment options with side effects besides discussing the global economic burden.

Matched MeSH terms: Arthritis, Rheumatoid/physiopathology

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