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Alemtuzumab as Remission Induction Therapy in Behçet Disease: A 20-year Experience

Mohammad AJ, Smith RM, Chow YW, Chaudhry AN, Jayne DR

J Rheumatol, 2015 Oct;42(10):1906-13.
PMID: 26276966 DOI: 10.3899/jrheum.141344

To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD).
Orbital and Optic Nerve Sheath Involvement and Pupil-Involving Cranial Nerve 3 Palsy in Giant Cell Arteritis

Dawoud SA, Ahmad NU, Shriver EM, Chung SM

J Rheumatol, 2024 Mar 01.
PMID: 38428963 DOI: 10.3899/jrheum.2023-1195

Giant cell arteritis (GCA) can present with atypical presentations that are diagnostically challenging. An 84-year-old woman with a history of breast adenocarcinoma treated with lumpectomy and radiation 2 years prior presented with a seizure-like episode.
Fulltext Musculoskeletal pain in Malaysia: a COPCORD survey

Veerapen K, Wigley RD, Valkenburg H

J Rheumatol, 2007 Jan;34(1):207-13.
PMID: 17216688

Objective. To assess the nature and extent of rheumatic complaints in a semirural area in a multiracial (Malay, Indian, Chinese) community in Malaysia using the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) protocol initiated by ILAR and the WHO.
Methods. All members of a community of 2700 persons over the age of 15 years were offered a questionnaire based interview in Phase 1 of the study. Those with rheumatic complaints (pain in the last 1 week) were invited for a physical examination by a rheumatologist in Phase 2.
Results. In total, 2594 (96%) persons agreed to a questionnaire based interview. Of those interviewed, 21.1% had a current rheumatic complaint. The pain rate was higher in women (23.8%) than in men (17.8%). Chinese men had the lowest age-standardized pain rate (9.9%), while Indian women had the highest rate (28.4%). In the study population, 14.4% complained of pain in the joints and/or musculoskeletal pain and 11.6% had low back pain. The knee was responsible for 64.8% of all complaints pertaining to the joints, and more than half those examined with knee pain had clinical evidence of osteoarthritis (OA). The complaint rate increased with age, up to 53.4% in the group age > 65 years. The major disability encountered was the inability to squat (3.1%). Fibromyalgia, soft tissue lesions, and localized OA of the knees were the main clinical diagnoses. Inflammatory arthritis was uncommon. Both Western and traditional sources of healthcare were used, often together. Self-medication was common (58.8%).
Conclusion. Knee and back pain are the main rheumatic complaints in Malaysia, with complaint rates differing according to race and gender.
Direct and indirect costs of osteoarthritis in Singapore: a comparative study among multiethnic Asian patients with osteoarthritis

Xie F, Thumboo J, Fong KY, Lo NN, Yeo SJ, Yang KY, et al.

J Rheumatol, 2007 Jan;34(1):165-71.
PMID: 17216684

OBJECTIVE:
To estimate and compare the direct and indirect costs of osteoarthritis (OA) in multiethnic Asian patients with OA in Singapore.

METHODS:
The study was a retrospective and cross-sectional design. Patients were stratified according to ethnicity and presence or absence of joint surgery. Direct costs were estimated from both a societal and a patient perspective using the Singapore General Hospital database; indirect costs were estimated using the human capital approach. All costs were expressed as mean costs per patient per annum in 2003 Singapore dollars.

RESULTS:
A total of 1179 patients (83.6% Chinese, 7.2% Malay, 3.5% Indian, 5.7% others) were included in estimating direct costs, of which 513 (43.5%) had total knee replacement (TKR) and 92 (7.8%) total hip replacement (THR), while 105 patients (71.4% Chinese, 14.3% Malay, 14.3% Indian) were included in estimating indirect costs. Direct costs to patients ranged from 1460 dollars to 7477 dollars for Chinese, 1362 dollars-7211 dollars for Malays, 1688 dollars-6226 dollars for Indians, and 1437 dollars-12,140 dollars for other ethnic patients; direct costs to society ranged from 3351 dollars to 15,799 dollars for Chinese, 2939 dollars-15,436 dollars for Malays, 3150 dollars-10,990 dollars for Indians, and 2597 dollars-17,879 dollars for other ethnic patients. In contrast, the indirect costs ranged from 1215 dollars to 3834 dollars for Chinese, 1138 dollars-6116 dollars for Malays, and 1371 dollars-5292 dollars for Indians. However, most ethnic variations were not statistically significant.

CONCLUSION:
The economic burden of OA to society and patients increased by 3-fold or more in the patients with TKR/THR compared to those without. The ethnic differences in health resources consumed were more apparent when the disease progressed.
Low prevalence of knee and back pain in southeast China; the Shantou COPCORD study

Zeng QY, Chen R, Xiao ZY, Huang SB, Liu Y, Xu JC, et al.

J Rheumatol, 2004 Dec;31(12):2439-43.
PMID: 15570648

To determine whether the previously noted low prevalence of knee pain (KP) and lumbar pain (LP) in rural southern China compared with the high prevalence observed in North China was also true in a southern urban population.
The effect of control and self-medication of chronic gout in a developing country. Outcome after 10 years

Darmawan J, Rasker JJ, Nuralim H

J Rheumatol, 2003 Nov;30(11):2437-43.
PMID: 14677190

OBJECTIVE: We describe a 10 year observation of the effect of control of hyperuricemia compared with self-medication alone in patients with chronic gout.
METHODS: We studied 299 consecutively self-referred Malayo-Polynesian men with chronic gout, mean age 35 +/- 14.3 SD years. Subjects comprised 228 cases with chronic gout without tophi or urolithiasis (Group 1) and 71 with those complications (Group 2). Attacks of acute gouty arthritis were treated with nonsteroidal antiinflammatory drugs (NSAID) and/or corticosteroids. After acute arthritis had settled, urate-lowering drugs were instituted in both groups combined with low dose colchicine and/or low dose NSAID for at least 0.5-2 years. Urate levels were maintained longterm at a mean of < 5 mg/dl. After 10 years, the dropouts were traced and evaluated for comparison with baseline and those who remained in the study. In Group 2 the urate-lowering drugs were continued.
RESULTS: Control of gout and hyperuricemia was achieved in all patients who remained under control: 91.6% of the 299 patients for at least 2 years (short-term), up to 5 years in 87.5% (medium term), and up to 10 years in 79.6% (longterm). In Group 1 (chronic gout without complication) only 36.8% had no attacks during 8 years, after they had tapered urate-lowering drug after the first 2 years of the study. In the 61 dropouts the intermittent symptomatic treatment and/or self-medication without longterm control of hyperuricemia resulted after 1 decade in chronic gout with more complications and associated conditions leading to increased morbidity, disability, and comorbidity, and 3 early mortalities.
CONCLUSION: By controlling hyperuricemia, improvement of the prognosis of chronic gout, comorbidity, and early death was achieved compared with self-medication alone. Self-medication in a developing country if continued unchecked may become a public health problem in a population with a high prevalence rate of gout.
WHO-ILAR COPCORD perspectives past, present, and future

Darmawan J, Muirden KD

J Rheumatol, 2003 Nov;30(11):2312-4.
PMID: 14677169
The effects of ethnicity on disease patterns in 472 Orientals with systemic lupus erythematosus

Thumboo J, Fong KY, Chng HH, Koh ET, Chia HP, Leong KH, et al.

J Rheumatol, 1998 Jul;25(7):1299-304.
PMID: 9676760

OBJECTIVE: To determine the effects of ethnicity on disease manifestations in Oriental patients with systemic lupus erythematosus (SLE) and to describe the risk of developing renal or central nervous system (CNS) involvement with time.
METHODS: A retrospective study of 472 patients with SLE seen at the only Rheumatology Unit in Singapore. The effect of ethnicity on selected disease manifestations at diagnosis was assessed after adjusting for demographic variables using multiple logistic regression. The probability of developing selected disease manifestations with time was determined using the Kaplan-Meier product limit method.
RESULTS: At diagnosis, Malays had a higher risk of renal or CNS involvement than Chinese (OR 2.26, 95% CI 1.21 to 4.21, and OR 3.07, 95% CI 1.01 to 9.34, respectively), and Indians a lower risk of malar rash and a higher risk of oral ulcers than Chinese (OR 0.30, 95% CI 0.13 to 0.68, and OR 2.90, 95% CI 1.45 to 7.34, respectively). The prevalence of renal or CNS involvement in the entire cohort increased with time, reaching 75.6% (95% CI 66.1% to 85.0%) and 16.7% (95% CI 11.7% to 21.6%), respectively, after 18 years of disease.
CONCLUSION: Ethnicity influenced disease manifestations at diagnosis in this cohort of Oriental patients with SLE. Renal or CNS involvement developed in previously unaffected patients up to 18 years after diagnosis, highlighting the need for continued vigilance in patients with lupus.
Patterns of psoriatic arthritis in Orientals

Thumboo J, Tham SN, Tay YK, Chee T, Mow B, Chia HP, et al.

J Rheumatol, 1997 Oct;24(10):1949-53.
PMID: 9330937

OBJECTIVE: To determine the clinical features of psoriatic arthritis (PsA) in a multiethnic Oriental population and to study the effect of ethnicity on disease patterns.
METHODS: A retrospective study of 80 patients with PsA seen at either a rheumatology or dermatology referral center. Patients and case records were reviewed and data abstracted according to a standard protocol. Eighty consecutive patients with psoriasis without PsA seen at the dermatology center were recruited as controls.
RESULTS: Asymmetric polyarthritis developing in the 4th decade with an equal male to female ratio was the commonest pattern of arthritis among Chinese, Indians, and Malays. Clinically apparent lumbar spondylitis was significantly more common in Indians than Chinese (10/11 vs 11/20, respectively; p = 0.046), although the prevalence of lumbar spondylitis was similar in all ethnic groups. Eighty-nine percent of subjects required nonsteroidal antiinflammatory drugs and 51% required disease modifying antirheumatic drugs at some time for control of joint disease. PsA was significantly more common among Indians compared to the ethnic distribution of the Singapore population (p < 0.000001). Multiple logistic regression identified Indian ethnicity as a risk factor for the development of PsA (OR 2.39, 95% confidence interval 1.02 to 5.60).
CONCLUSION: The commonest pattern of PsA in all ethnic groups was asymmetric polyarthritis. Ethnicity affected the development and presentation of PsA in our series: Indians with psoriasis had double the risk of developing PsA compared to Chinese with psoriasis, and lumbar spondylitis when present in Chinese subjects was asymptomatic in 45%, being detectable only on radiological examination.
Tophaceous gout in young patients with systemic lupus erythematosus

Veerapen K, Schumacher HR, van Linthoudt D, Neilson EG, Wang F

J Rheumatol, 1993 Apr;20(4):721-4.
PMID: 8496872

Systemic lupus erythematosus (SLE) and gout have been associated infrequently. We describe 3 young adults with SLE who developed tophaceous gout relatively early in the course of their disease. All were underexcretors of uric acid but were studied after the development of renal disease; 2 were treated with diuretics. In 2 cases, gout became obvious while lupus was quiescent.
Proceedings of OMERACT 10, the International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials. May 4-8, 2010. Kota Kinabalu, Borneo

J Rheumatol, 2011 Jul;38(7):1448-518.
PMID: 22263235
CXCL 9 and CXCL 10 as Sensitive markers of disease activity in patients with rheumatoid arthritis

Kuan WP, Tam LS, Wong CK, Ko FW, Li T, Zhu T, et al.

J Rheumatol, 2010 Feb;37(2):257-64.
PMID: 20032101 DOI: 10.3899/jrheum.090769

OBJECTIVE:
To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.

METHODS:
Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.

RESULTS:
The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).

CONCLUSION:
Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.
Study done in Hong Kong
A patient with progressive shortening of the fingers

Letchumanan P, Thumboo J, Leong RT

J Rheumatol, 2009 Jan;36(1):198-9.
PMID: 19208534 DOI: 10.3899/jrheum.080859
A comparison of calcium, calcitriol, and alendronate in corticosteroid-treated premenopausal patients with systemic lupus erythematosus

Yeap SS, Fauzi AR, Kong NC, Halim AG, Soehardy Z, Rahimah I, et al.

J Rheumatol, 2008 Dec;35(12):2344-7.
PMID: 19004038 DOI: 10.3899/jrheum.080634

OBJECTIVE: To assess bone mineral density (BMD) changes in patients with systemic lupus erythematosus (SLE) undergoing longterm therapy with corticosteroids (CS) while taking calcium, calcitriol, or alendronate. The primary endpoint was BMD changes at 2 years.
METHODS: Premenopausal SLE patients were randomized into 3 groups according to medication: calcium carbonate 500 mg bd (calcium alone), calcitriol 0.25 microg bd plus calcium carbonate 500 mg bd (calcitriol + calcium), and alendronate 70 mg/week plus calcium carbonate 500 mg bd (alendronate + calcium). BMD was measured at baseline and at the end of the first and second years.
RESULTS: Ninety-eight patients were recruited. There were 33 patients taking calcium alone, 33 calcitriol + calcium, and 32 alendronate + calcium. On randomization, median duration of CS use was 2.5 years (range 0-20 yrs). Seventy-seven patients (78.6%) completed the study (23 taking calcium alone, 27 calcitriol + calcium, 27 alendronate + calcium). There were no significant differences in mean CS dosages among the 3 groups at the time of BMD measurements. After 2 years, there were no significant changes in BMD in the calcium-alone and calcitriol + calcium groups, apart from a 0.93% (p < 0.001) reduction in total hip BMD in the calcium-alone group. In contrast, the alendronate + calcium group showed significant increases in BMD of 2.69% (p < 0.001) in the lumbar spine and 1.41% (p < 0.001) in total hip.
CONCLUSION: Both calcium alone and calcitriol + calcium preserved lumbar spine BMD in premenopausal patients with SLE taking longterm CS at 2 years, whereas alendronate + calcium led to increases in BMD in lumbar spine and total hip. Premenopausal women taking CS should be considered for osteoporosis prophylaxis.
Study site: Outpatient clinics in 2 teaching hospitals in Kuala Lumpur, Malaysia
Fulltext Longterm Drug Survival of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis

Emery P, Vlahos B, Szczypa P, Thakur M, Jones HE, Woolcott J, et al.

J Rheumatol, 2020 04;47(4):493-501.
PMID: 31154413 DOI: 10.3899/jrheum.181398

OBJECTIVE: To evaluate longterm drug survival (proportion of patients still receiving treatment) and discontinuation of etanercept (ETN), infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP), and golimumab (GOL) using observational data from patients with rheumatoid arthritis (RA).
METHODS: Following a systematic literature review, drug survival at 12 and 12-24 months of followup was estimated by summing proportions of patients continuing treatment and dividing by number of studies. Drug survival at ≥ 36 months of followup was estimated through Metaprop.
RESULTS: There were 170 publications included. In the first-line setting, drug survival at 12 months with ETN, IFX, or ADA was 71%, 69%, and 70%, respectively, while at 12-24 months the corresponding rates were 63%, 57%, and 59%. In the second-line setting, drug survival at 12 months with ETN, IFX, or ADA was 61%, 69%, and 55%, respectively, while at 12-24 months the corresponding rates were 53%, 39%, and 43%. Drug survival at ≥ 36 months with ETN, IFX, or ADA in the first-line setting was 59% (95% CI 46-72%), 49% (95% CI 43-54%), and 51% (95% CI 41-60%), respectively, while in the second-line setting the corresponding rates were 56% (95% CI 52-61%), 48% (95% CI 40-55%), and 41% (95% CI 36-47%). Discontinuation of ETN, IFX, and ADA at 36 months of followup was 38-48%, 42-62%, and 38-59%, respectively. Data on CZP and GOL were scarce.
CONCLUSION: After > 12 months of followup, more patients with RA receiving ETN remain on treatment compared with other tumor necrosis factor inhibitors.
Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State In Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus

Golder V, Kandane-Rathnayake R, Louthrenoo W, Chen YH, Cho J, Lateef A, et al.

J Rheumatol, 2024 May 01.
PMID: 38490668 DOI: 10.3899/jrheum.2023-0900

OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE).
METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare.
RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up.
CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

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