1.Dual rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity affects the manifestations of rheumatoid arthritis.
Li Huan Angela Marie CHAN ; Khai Pang LEONG ; Justina Wei Lynn TAN ; Xiao GAO ; Wei Qiang SEE ; Ee Tzun KOH
Singapore medical journal 2025;66(9):486-491
INTRODUCTION:
Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically.
METHODS:
We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups.
RESULTS:
Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life.
CONCLUSIONS
RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans
;
Arthritis, Rheumatoid/diagnosis*
;
Male
;
Female
;
Middle Aged
;
Rheumatoid Factor/blood*
;
Anti-Citrullinated Protein Antibodies/blood*
;
Adult
;
Quality of Life
;
Prospective Studies
;
Antirheumatic Agents/therapeutic use*
;
Aged
;
Peptides, Cyclic/immunology*
;
Prednisolone/therapeutic use*
;
Surveys and Questionnaires
;
Severity of Illness Index
;
Prognosis
2.Association between bone mineral density and vascular health in rheumatoid arthritis.
Chuanhui XU ; Yi Wye LAI ; Shih-Huan CHOU ; Xiaoe ZHANG ; Ee Tzun KOH ; Rinkoo DALAN ; Khai Pang LEONG
Singapore medical journal 2025;66(3):147-153
INTRODUCTION:
Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD).
METHODS:
We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2.
RESULTS:
We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV.
CONCLUSION
Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans
;
Arthritis, Rheumatoid/complications*
;
Female
;
Male
;
Bone Density
;
Middle Aged
;
Cross-Sectional Studies
;
Vascular Stiffness
;
Aged
;
Singapore
;
Pulse Wave Analysis
;
Osteoporosis/complications*
;
Endothelium, Vascular/physiopathology*
;
Cardiovascular Diseases/complications*
;
Carotid-Femoral Pulse Wave Velocity
;
Hyperemia
3.Singapore Chapter of Rheumatologists Consensus Statement on the Eligibility for Government Subsidy of Biologic Disease Modifying Antirheumatic Agents for Treatment of Rheumatoid Arthritis (RA).
Gim Gee TENG ; Peter P CHEUNG ; Manjari LAHIRI ; Jane A CLAYTON ; Li Ching CHEW ; Ee Tzun KOH ; Wei Howe KOH ; Tang Ching LAU ; Swee Cheng NG ; Bernard Y THONG ; Archana R VASUDEVAN ; Jon K C YOONG ; Keng Hong LEONG
Annals of the Academy of Medicine, Singapore 2014;43(8):400-411
INTRODUCTIONUp to 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional non-biologic disease modifying antirheumatic drugs (nbDMARDs), and may benefit from therapy with biologic DMARDs (bDMARDs). However, the high cost of bDMARDs limits their widespread use. The Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore aims to define clinical eligibility for government-assisted funding of bDMARDs for local RA patients.
MATERIALS AND METHODSEvidence synthesis was performed by reviewing 7 published guidelines on use of biologics for RA. Using the modified RAND/UCLA Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations.
RESULTSTen recommendations including diagnosis of RA, choice of disease activity measure, initiation and continuation of bDMARD and option of first and second-line therapies were formulated. The panellists agreed that a bDMARD is indicated if a patient has (1) active RA with a Disease Activity Score in 28 joints (DAS28) score of ≥3.2, (2) a minimum of 6 swollen and tender joints, and (3) has failed a minimum of 2 nbDMARD combinations of adequate dose regimen for at least 3 months each. To qualify for continued biologic therapy, a patient must have (1) documentation of DAS28 every 3 months and (2) at least a European League Against Rheumatism (EULAR) moderate response by 6 months after commencement of therapy.
CONCLUSIONThe recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARDs usage accessible and equitable to eligible patients in Singapore.
Antirheumatic Agents ; economics ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Financing, Government ; Humans ; Practice Guidelines as Topic ; Singapore
4.Outcomes of chronic hepatitis B infection in Oriental patients with rheumatic diseases.
Bernard Y H THONG ; Ee Tzun KOH ; Hiok Hee CHNG ; Wan Cheng CHOW
Annals of the Academy of Medicine, Singapore 2007;36(2):100-105
INTRODUCTIONThe aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases.
MATERIALS AND METHODSThis is a retrospective consecutive, non-comparative study.
RESULTSThe majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 +/- 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 +/- 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 +/- 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti- HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 +/- 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma.
CONCLUSIONElevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; Asian Continental Ancestry Group ; Comorbidity ; Female ; Glucocorticoids ; therapeutic use ; Hepatitis B, Chronic ; epidemiology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Lamivudine ; therapeutic use ; Lupus Erythematosus, Systemic ; drug therapy ; Male ; Middle Aged ; Prednisolone ; therapeutic use ; Retrospective Studies ; Rheumatic Diseases ; epidemiology ; Treatment Outcome ; Virus Activation

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