Rheumatol Int (2017) 37:1719–1725

DOI 10.1007/s00296-017-3772-8
Rheumatology
INTERNATIONAL

OBSERVATIONAL RESEARCH

Real‑world clinical experience of biological disease modifying

anti‑rheumatic drugs in Malaysia rheumatoid arthritis patients
Bee Eng Tan1 · Ai Lee Lim1 · Sow Lai Kan1 · Chong Hong Lim1 · Esther Ee Ling Tsang1 · Shereen Suyin Ch’ng2 ·
Nadiah Mohd Noor3 · Nurulraziquin Mohd Jamid4,9 · Cheng Lay Teh5 · Rachel Joshua Thundyil6,12 · Yet Lin Loh7 ·
Hwee Cheng Chong8 · Swee Gaik Ong10 · Asmahan Mohamed Ismail11 · Yvonne Y. L. Lee13 · Suk Chyn Gun3 

Received: 5 January 2017 / Accepted: 29 June 2017 / Published online: 10 July 2017
© Springer-Verlag GmbH Germany 2017

Abstract  The effect of biologic disease modifying anti-
rheumatic drugs (bDMARDs) in treating rheumatoid arthri-
tis (RA) in real-world clinical practice remains unknown in
Southeast Asia. We aimed to assess the efficacy and safety
of bDMARDs among Malaysian RA patients treated in
routine clinical practice. A retrospective medical chart
review of RA patients from 11 government hospitals were
conducted from January 2003 to January 2014. A stand-
ardized questionnaire was used to abstract patient’s demo-
graphic, clinical and treatment data. Level of disease activ-
ity was measured by DAS28 collected at baseline, 3, 6 and
12  months. Three hundred and one patients were avail-
able for analysis, mean age 41 (SD, 10.8) years, mean RA
duration 12.3 (SD, 6.9) years and 98% had history of two
or more conventional-synthetic DMARDs. There were
467 bDMARD courses prescribed with mean bDMARDs
duration use of 12.9  months (SD 14.7). Tumour necrosis
factor alpha inhibitors were the most common prescribed
bDMARDs (77.1%), followed by Tocilizumab (14.6%) and
Rituximab (8.4%). We observed significant improvement in
mean DAS28 values from baseline to 3, 6 and 12  months
(p  <  0.001). Overall, 16.9% achieved DAS28 remission
at 6  months. A third (35.6%) of patients reported adverse
events, three commonest being infections (46.5%), allergy
(22.9%) and laboratory abnormalities (12.9%). 3.7% of
our patients had tuberculosis. Biologic DMARDs were
effective in treating RA in real-world practice in Malay-
sia, despite a lower remission rate compared to developed
countries. Except for higher rates of tuberculosis, the AEs
were similar to the published reports.
Keywords  Biologics · Efficacy · Real world ·
Rheumatoid arthritis · Safety · Southeast Asia

7
* Bee Eng Tan Department of Medicine, Hospital Sultan Ismail,
tbeeng3@yahoo.com Johor Baharu, Johor Bahru, Malaysia
8
1 Department of Medicine, Hospital Melaka, Malacca City,
Rheumatology Unit, Department of Medicine, Hospital Melaka, Malaysia
Pulau Pinang, Jalan Residensi, 10990 Georgetown, Penang,
9
Malaysia Department of Medicine, Hospital Tengku Ampuan
2 Rahimah, Klang, Selangor, Malaysia
Rheumatology Unit, Department of Medicine, Hospital
10
Selayang, Batu Caves, Selangor, Malaysia Department of Medicine, Hospital Kuala Lumpur,
3 Kuala Lumpur, Wilayah Persekutuan, Malaysia
Rheumatology Unit, Department of Medicine, Hospital
11
Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia Department of Medicine, Hospital Raja Perempuan Zainab
4 II, Kota Baharu, Kelantan, Malaysia
Rheumatology Unit, Department of Medicine, Hospital
12
Putrajaya, Putrajaya, Wilayah Persekutuan, Malaysia Department of Medicine, University Malaysia Sabah,
5 Kota Kinabalu, Sabah, Malaysia
Rheumatology Unit, Department of Medicine, Hospital
13
Umum Sarawak, Kuching, Sarawak, Malaysia Outcome and Evidence, Health and Value, Pfizer Malaysia
6 Sdn Bhd, Kuala Lumpur, Wilayah Persekutuan, Malaysia
Department of Medicine, Hospital Queen Elizabeth I,
Kota Kinabalu, Sabah, Malaysia

13
Vol.:(0123456789)

1720
Introduction
There is a major shift of treatment strategy in rheuma-
toid arthritis (RA) with emphasis on the use of biologic
disease modifying anti-rheumatic drugs (bDMARDs) in
patients who have inadequate response or intolerance to
conventional-synthetic DMARDs (csDMARDs) [1–3]. In
a consensus statement on bDMARDs, the Malaysian Soci-
ety of Rheumatology (MSR) recommended bDMARDs be
prescribed to RA patients showing persistent high disease
activity who are intolerance or have sub-optimal response
to two or more csDMARDs in two separate clinic visits [4].
Biologic disease modifying anti-rheumatic drugs
(bDMARDs) have been shown to be effective in the treat-
ment of rheumatoid arthritis (RA) in systematic reviews of
clinical trials [5–7]. However, the real-world patients are
very different from those in clinical trials [8, 9]. Thus far,
there is no published report on the benefit of bDMARDs
in real-world clinical practice in Southeast Asia. Further-
more, it is inappropriate to apply the results of clinical tri-
als to the multi-ethnic Malaysian populations who have
different socio-cultural background living in a unique
healthcare system. A developing country with 28.5 million
population consisting of three major ethnic groups: Bumi-
putera [67.3% (Malays 54.5% and other indigenous groups
12.8%)], Chinese (24.5%) and Indians (7.3%) [10], Malay-
sia has a GDP per-capita of USD 11, 305 in 2014 [11]. The
healthcare system in Malaysia is made up of a universal,
tax-funded, government-run public healthcare, in which
patients only pays minimal fees (2–3% of total healthcare
fees), and the fast-growing private healthcare facilities [12].
Besides, there is a lack of comprehensive review of all
available biologics in one study as majority reported single
biologic efficacy within the study population.
This study aimed to examine the efficacy and safety of
bDMARDs in RA patients treated in routine clinical prac-
tice in Malaysia.
Methods
In this retrospective study, we reviewed medical chart of
RA patients who were treated with bDMARDs from 11
government-funded hospitals between January 2003 and
January 2014. RA was diagnosed according to American
College of rheumatology (ACR) 1987 [13] or 2010 ACR/
European League Against Rheumatism (ACR/EULAR) cri-
teria [14]. RA activity was measured using Disease Activity
Score of 28 joints (DAS28) by erythrocyte sedimentation
rate (ESR) and/or C-reactive protein (CRP). Disease activ-
ity, adverse events and reasons for discontinuation assess-
ments were retrieved at baseline (the first date bDMARDs
were prescribed), 3, 6 and 12  months of treatment.
13
Rheumatol Int (2017) 37:1719–1725
Socioeconomic status was classified based on Economic
Planning Unit Malaysia, 2014 [15]. Multiple imputations
(MI) were computed for DAS28-ESR and DAS28-CRP
scores at respective follow-up assessment time point if 20%
of the data is missing. Imputations were applied using mul-
tivariate normal regression which uses iterative Markov
chain Monte Carlo method. It accommodates arbitrary
missing value pattern [16, 17]. We reanalysed the mean
statistics using MI estimates for the imputed DAS28-ESR
and DAS28-CRP. All statistical analyses were performed
with STATA 13 software (StataCorp. 2013. Stata Statistical
Software: Release 13. College Station, TX: StataCorp LP.).
Significance level was established at p < 0.05.
Results
Baseline characteristics
The demographic characteristics of all our 301 patients
were presented in Table 1. The mean age at diagnosis was
41 years (SD 10.8), mean disease duration was 12.3 years
(SD 6.9) and females were accounted for 84% of the study
cohort. Majority (74.7%) of the patients’ socioeconomic
status was at bottom 40% in comparison to the general
population as per income classification based on Economic
Planning Unit Malaysia. Only 10.5% of the patients had
personal insurance. Full time employment rate was consid-
erably low in this cohort (29.5%).
Treatments prior to initiation of the first bDMARDs
98% of our patients had been treated with at least two csD-
MARDs (33.6% and 44.4 had 3 and 4 csDMARDs, respec-
tively) prior to initiation of the first bDMARDs. Methotrex-
ate was the most prescribed csDMARDs (97.7%), followed
by sulphasalazine (88%), leflunomide (82%) and hydroxy-
chloroquine (60%). These csDMARDs were used alone or
in combinations. Other sDMARDs prescribed were cyclo-
sporin A (9%), azathioprine (2.3%), cyclophosphamide
(1.3%), penicillamine (1.3%) and chloroquine (0.7%). Six
months prior to initiation of the first bDMARDs, 84.3%
had nonsteroidal inflammatory drugs or cyclooxygenase-2
inhibitors and 75% were on corticosteroid apart from com-
bination of csDMARDs.
Biologic DMARDs
467 courses of biologics DMARDs were prescribed among
the 301 patients, with 40% of them treated with two or
more bDMARDs. TNF alpha inhibitors were the most pre-
scribed biologics agents (77.1%), followed by IL-6 inhibi-
tor (Tocilizumab) (14.6%), and B cell inhibitor (Rituximab)
Rheumatol Int (2017) 37:1719–1725 1721

Table 1  Baseline patient characteristics Table 2  Biologic DMARDs treatment

N = 301 n (%) n %

Age (years), mean (SD) 51.8 (10.2) Number of bDMARDs used per patient, 1 (1–5)
Disease duration (years), mean (SD) 12.3 (6.9) median (range)
Gender Current bDMARD courses 112 24
 Female 253 84  Etanercept 39
 Male 48 16  Tocilizumab 33
Ethnicity  Adalimumab 25
 Malay 128 42.7  Infliximab 7
 Chinese 79 26.3  Golimumab 4
 Indian 75 24.9  Rituximab 4
 Others 19 6.3 Past bDMARD courses 355 76
Marital status  Etanercept 102
 Single 5 1.7  Tocilizumab 35
 Married 254 86.7  Adalimumab 102
 Divorced 30 10.2  Infliximab 52
 Widowed 4 1.4  Golimumab 29
Education level  Rituximab 35
 None 8 4.7 bDMARDS biologic disease modifying anti-rheumatic drugs
 Primary 53 31
 Secondary 84 49.1
 Tertiary 26 15.2 3 months (p < 0.001), 6 months (p < 0.001) and 12 months
Household income (MYR) (p  <  0.001). We observed mean DAS28 scores were
 ≤1000 66 37.1 reduced from minimum of 1.2 to maximum of 2.4 across
 1001–3000 67 37.6 the follow-up intervals. Minimal reduction of mean
 3001–5000 28 15.7 DAS28-ESR scores (less than 0.7) were observed in
 5001–7000 5 2.8 between intervals such as month 3 to month 6, month 3 to
 >7000 12 6.7 month 12 and month 6 to month 12. Patients who received
 Personal insurance 21 10.5 IL-6 inhibitor had significant greater reduction in DAS28
Employment status scores compared to TNF and B-cell inhibitors at 3 months
 None 48 17.1 (p  <  0.001) and 6  months (p  <  0.0086), respectively. We
 Homemaker 100 35.6 reanalysed changes of mean DAS28-ESR and DAS29-
 Full time 83 29.5 CRP based on imputation of missing scores over the fol-
 Part time 11 3.9 low-up time points. Imputation results were similar to the
 Retired 39 13.9 complete-case analyses (data not shown). Variations in the
SD standard deviation, MYR Malaysian Ringgit—local currency disease activity categories stratified by DAS28 scores and
biologic agents were illustrated in Fig. 1. At baseline 62.1%
had high disease activity and 34.7% had moderate disease
(8.4%). On average, patients were on biologic courses for activity. The overall remission rate at 6 and 12 months were
12.9  months (SD 14.7). Frequency of each bDMARDS 16.9 and 18.9%, respectively.
used was presented in Table 2.
Discontinuation of bDMARDs was observed in 76% of Biologic DMARDs safety
the treatment courses and 23% discontinued at six months.
The reason for discontinuation included treatment failure Approximately a third (35.6%) of RA patients treated
(38.3%), adverse event (16.1%), lack of funding (14.2%), with bDMARDs reported adverse events (AEs). Infec-
end of clinical trial (13.7%), remission (6.8%) and patients’ tions (respiratory tract infection, tuberculosis, varicella
preference (5.7%). zoster and cutaneous fungal infection) were the most com-
mon recorded AE, comprising 46.5% of all AEs. This was
Biologic DMARDs efficacy followed by allergy (rashes, infusion reaction and injec-
tion site reaction) (22.9%) and lab abnormalities (raised
There was significant improvement in DAS2-ESR scores liver enzymes and mild cytopenias) (12.9%). None of
for overall and individual bDMARDs from baseline to the patients discontinued bDMARDs due to laboratory

13

1722
Fig. 1  Changes of disease severity from baseline to 12 months of bDMARDs treatment
abnormalities. Figure  2 illustrated the frequency and pro-
portion of the three most common AEs across the biologic
agents.
Tuberculosis screening and surveillance
A standard screening of tuberculosis (TB) which included
chest radiograph, tuberculin skin testing was performed to
all patients prior to initiation of bDMARDs. TB was diag-
nosed in 11 patients (3.7%), of which six cases were TNF
inhibitor users, three were Tocilizumab users and two were
Rituximab users. The median duration of exposure to bio-
logic DMARDs before the diagnosis of TB was 6 months
(range 2–17). Three patients developed TB within three
months of biologic DMARDs therapy. One developed PTB
at 12 months after the last infusion of rituximab.
Pregnancy
Three patients conceived during the course of bDMARDs
treatment. One patient was receiving tocilizumab, metho-
trexate and hydroxychloroquine when she was confirmed
pregnant at 6  weeks of periods of amenorrhoea (POA),
upon which tocilizumab and methotrexate were discontin-
ued promptly. She underwent lower segment caesarean sec-
tion at 37 weeks for reduced liquor. The baby’s birth weight
13
Rheumatol Int (2017) 37:1719–1725
was low at 1.95 kg but was otherwise normal. The second
patient who was treated with etanercept decided to continue
etanercept throughout the pregnancy. She had spontaneous
vaginal delivery at 37  weeks, with baby’s birth weight at
2.4 kg. The third patient was taking adalimumab and leflu-
nomide until diagnosed pregnant at 9 weeks POA. Despite
discontinuation of adalimumab and leflunomide elimina-
tion therapy, she developed urosepsis at 27  weeks POA,
which resulted a macerated still-birth of a 1.1 kg baby. This
patient later succumbed to sepsis, post-partum hemorrhage
and disseminated intravascular coagulopathy. There were
no gross fetal abnormalities noted in all three babies.
Other observations
A case of B cell non-Hodgkin lymphoma (NHL) in a
52-year-old Indian man was reported in this cohort. He had
RA for 13 years and the duration of adalimumab exposure
was 42 months before the diagnosis of NHL.
Discussion
This is the first report on the efficacy and safety of
bDMARDs in the real-world clinical practice in South-
east Asia. Even though this study was only carried out in
Rheumatol Int (2017) 37:1719–1725 1723
90
Infecon
80
70
60
Number of adverse events
50
40
30
20
10
0 0
All biologics
Fig. 2  Proportions and common adverse events across biologic agents among rheumatoid arthritis patients
11 government funded hospitals in Malaysia, our data is
very likely to be representative of the actual Malaysian RA
patients for two reasons. First, the public healthcare system
serves the majority of the Malaysian population, providing
56% of total health expenditure in 2009 [12], and second,
65% of Malaysian rheumatologists practice in government
hospitals (according to the record of Malaysian Society of
Rheumatology). We found that bDMARDs treatment were
effective in improving patients’ DAS28 despite the use
after failing at least two csDMARDs and in patients with
long disease duration. Nevertheless, our remission rate was
lower as compared to the biologic registries from devel-
oped countries.
We observed similar efficacy in comparison to Dutch’s
DREAM biologic registry [18] which showed TNF inhibi-
tors had effectively reduced the mean DAS28-ESR from
5.00 (SD 1.32) to 3.49 (SD 1.34) at 6 months (p < 0.001)
in RA patients with median RA duration of 5.9 years, who
had failed at least 2 csDMARDs. However, the remission
rates among our patients were much lower. Only 13.2%
of our TNF alpha inhibitor users achieved DAS28 remis-
sion at six months, compared to DREAM (27%) [18] and
RABBIT (30.6%) [19] registries. The lower remission rate
could be due to a later use of bDMARDs and differences
in disease manifestations among our patients compared to
developed countries. Due to high treatment cost, Malaysian
RA patients have limited access to biologic therapies. With
50
Allergy Lab abnormalies
45
40
Proporon of RA paents with adverse events
35
30
25
20
15
10
5
An-TNF B-cell inhibitor IL-6 inhibitor
Biologic agents
a GDP per-capita of USD 11,305 (approximately RM 48,
611) [11], it is not feasible for most patients to self-fund the
bDMARDs therapy which costs approximately RM45,000/
year. Most patients rely on assistance from welfare depart-
ments and the tight government hospital budget alloca-
tion to fund their biologic therapy. Only a minority of the
patients who are more affluent can pay for their own treat-
ment or have insurance policies that fund the treatment. In
addition, the disease manifestations among Malaysian RA
patient had been reported to be different. Veerapen had
found that Malaysian patients had more frequent involve-
ment of the wrists and cervical spine when compared to
British patients [20]. This difference might contribute to
the higher DAS28 in our cohort.
Our reported AE were expected as disclosed in clinical
trials. However, the proportion of TB in our cohort was
much higher compared to other registries; BSRBR (0.37%)
[21] and HKBR (1.88%) [22]. This can be explained by
higher background rate of TB in Malaysia.
Interestingly, Indian patients were over-represented
compared to the population distribution (24.9 vs 7.3%)
(10), a finding similar to a report of the Malaysian RA reg-
istry [23]. This could be explained by genetic variances the
ethnic groups, as reported by Kong [24] and Chun-Lai [25].
In addition, cultural and dietary diversities might affect the
disease prevalence, which warrant large and well-designed
epidemiological studies.
13

1724
The limitations in this study included the absence of
concomitant medications, and the inconsistent use of
DAS28-ESR and DAS28-CRP across various hospitals
which contributed to incomplete DAS28-ESR values. In
addition, DAS28 might not be suitable for patients who
had prominent ankle, tarsal, MTP and IP toes involvement,
which were not calculated in DAS28.
Conclusion
Biologic DMARDs were effective in treating RA in real-
world clinical practice in Malaysia, despite a lower remis-
sion rate compared to developed countries. Except for
higher rates of tuberculosis, the AEs were similar to the
published reports.
Acknowledgements  The authors thank all the rheumatologists and
rheumatology trainees who helped in the data collection in the partici-
pating MOH hospitals. We also thank the director general, Ministry of
Health Malaysia for permission to publish this article.
Compliance of ethical standards  Malaysia, 2000–2010. Accessed 16 May 2017
Funding  No funding received for conduct of this study.
Conflict of interest  Author Yvonne Lee YL is an employee of Pfizer
Malaysia. Author Bee Eng Tan, Ai Lee Lim, Sow Lai Kan, Chong
Hong Lim, Esther Ee Ling Tsang, Shereen Suyin Ch’ng, Nadiah Mohd
Noor, Nurulraziquin, Mohd Jamid, Cheng Lay Teh, Rachel Joshua
Thundyil, Yet Lin Loh, Hwee Cheng Chong, Swee Gaik Ong, Asma-
han Mohamed Ismail, and Suk Chyn Gun declare that they have no
conflicts of interest.
Ethical approval  All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
standards.
References
1. Quan LD, Thiele GM, Tian J, Wang D (2008) The development
of novel therapies for rheumatoid arthritis. Expert Opin Ther Pat
18(7):723–738. doi:10.1517/13543776.18.7.723
2. van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman
YP, van Zeben D, Kerstens PJ, Gerards AH, van Groenendael
JH, Hazes JM, Breedveld FC, Allaart CF, Dijkmans BA (2007)
Limited efficacy of conventional DMARDs after initial metho-
trexate failure in patients with recent onset rheumatoid arthritis
treated according to the disease activity score. Ann Rheum Dis
66(10):1356–1362. doi:10.1136/ard.2006.066662
3. Choy EH, Smith C, Dore CJ, Scott DL (2005) A meta-analysis
of the efficacy and toxicity of combining disease-modifying anti-
rheumatic drugs in rheumatoid arthritis based on patient with-
drawal. Rheumatology (Oxford) 44(11):1414–1421. doi:10.1093/
rheumatology/kei031
13
Rheumatol Int (2017) 37:1719–1725
4. Inflammatory arthritis and biologic therapy—Malaysian consensus.
Malaysian Society of Rheumatology, November 2014. Available on
MSR official website: http://www.msr.my. Accessed 17 Jan 2017
5. Singh JA, Beg S, Lopez-Olivo MA (2010) Tocilizumab for rheu-
matoid arthritis. Cochrane Database Syst Rev, Issue 7. Art. No.:
CD008331. doi:10.1002/14651858.CD008331.pub2
6. Lopez-Olivo MA, Amezaga Urruela M, McGahan L, Pol-
lono EN, Suarez-Almazor ME (2015) Rituximab for rheuma-
toid arthritis. Cochrane Database Syst Rev, Issue 1. Art. No.:
CD007356. doi:10.1002/14651858.CD007356.pub2
7. Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W
et  al (2006) A systematic review of the effectiveness of adali-
mumab, etanercept and infliximab for the treatment of rheuma-
toid arthritis in adults and an economic evaluation of their cost-
effectiveness. Health Technol Assess 10:1–229
8. Sokka T, Pincus T (2003) Eligibility of patients in routine care
for major clinical trials of anti-tumor necrosis factor alpha
agents in rheumatoid arthritis. Arthritis Rheum 48(2):313–318.
doi:10.1002/art.10817
9. Zink ASA, Schneider M, Herzer P, Hierse F, Stoyanova-Scholz
M, Wassenberg S, Kapelle A, Listing J (2006) Effectiveness of
tumor necrosis factor inhibitors in rheumatoid arthritis in an
observational cohort study: comparison of patients according
to their eligibility for major randomized clinical trials. Arthritis
Rheum 54(11):3399–3407
10. Malaysia DoS (2010) Intercensal mid-year population estimates
for 2001–2009, Table A Summary of Population Statistics,
11. The World Bank DoS (2010). Current international GDP per
capita. http://data.worldbank.org/indicator/NY.GDP.PCAP.KD.
Accessed 16 May 2017
12. Jaafar S, Noh KM, Muttalib KA, Othman NH, Healy J (2013)
Malaysia health system review. Health systems in transition Vol.
3 No. 1 2013. World Health Organization 2012
13. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF,
Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al
(1988) The American Rheumatism Association 1987 revised
criteria for the classification of rheumatoid arthritis. Arthritis
Rheum 31(3):315–324
14. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham
CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD,
Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli
G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J,
Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden
RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D,
Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010)
2010 Rheumatoid arthritis classification criteria: an American
College of Rheumatology/European League Against Rheuma-
tism collaborative initiative. Arthritis Rheum 62(9):2569–2581.
doi:10.1002/art.27584
15. Malaysia DoS (2014) Household income and poverty. http://
www.epu.gov.my/en/householdincome-poverty. Accessed 19
Nov 2015
16. Allison PD (2001) Missing data. SAGE, Thousand Oaks
17. Schafer JL (1997) Analysis of incomplete multivariate data.
Chapman & Hall, Boca Raton
18. de Punder YM, Fransen J, Kievit W, Houtman PM, Visser H,
van de Laar MA, van Riel PL (2012) The prevalence of clini-
cal remission in RA patients treated with anti-TNF: results from
the Dutch Rheumatoid Arthritis Monitoring (DREAM) regis-
try. Rheumatology (Oxford) 51(9):1610–1617. doi:10.1093/
rheumatology/kes078
19. Listing J, Strangfeld A, Rau R, Kekow J, Gromnica-Ihle E,
Klopsch T, Demary W, Burmester GR, Zink A (2006) Clinical
and functional remission: even though biologics are superior to
conventional DMARDs overall success rates remain low–results
Rheumatol Int (2017) 37:1719–1725 1725
from RABBIT, the German biologics register. Arthritis Res Ther
8(3):R66. doi:10.1186/ar1933
20. Veerapen K (1993) The expression of rheumatoid arthritis in
Malaysian and British patients. DBr J Rheumatol:541–545
21. Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J,
Ustianowski A, Consortium BSRBRCC, Symmons DP, Regis-
ter BSRB (2010) Drug-specific risk of tuberculosis in patients
with rheumatoid arthritis treated with anti-TNF therapy: results
from the British Society for Rheumatology Biologics Regis-
ter (BSRBR). Ann Rheum Dis 69(3):522–528. doi:10.1136/
ard.2009.118935
22. Mok C-C (2012) The Hong Kong society of rheumatology bio-
logics registry: updated report (June 2012).  Hong Kong Bull
Rheum Dis 12:25–26
23. Ch’ng SS, Lau IS, Zain MM, Yusoof HM, Baharuddin H, Ahmad
A, Mokhtar I, Rosman A (2016) Characteristics of patients with
rheumatoid arthritis (RA) in a multi-ethnic cohort: results from
the National Inflammatory Arthritis Registry (NIAR). Int J
Rheum Dis 19(Suppl. 2):21–293
24. Kong KF, Yeap SS, Chow SK, Phipps ME (2002) HLA-DRB1
genes and susceptibility to rheumatoid arthritis in three ethnic
groups from Malaysia. Autoimmunity 35(4):235–239
2 5. Chun-Lai T, Padyukov L, Dhaliwal JS, Lundström E, Yahya A,
Muhamad NA, Klareskog L, Alfredsson L, Larsson PT, Murad S,
Malaysian Epidemiological Investigation of Rheumatoid Arthri-
tis (MyEIRA) Study Group (2011) Shared epitope alleles remain
a risk factor for anti-citrullinated proteins antibody (ACPA)—
positive rheumatoid arthritis in three Asian ethnic groups. PLoS
One 6(6):e21069. doi:10.1371/journal.pone.0021069
13