RHEUMATOLOGY
Letters to the Editor
Rheumatology 2017;56:660661
doi:10.1093/rheumatology/kew460
Advance Access publication 30 December 2016
Rheumatology key message
L ET T E R
.
Socio-economic status is under-reported in
randomized controlled trials of biologic DMARDs
in RA.
SIR, randomized control trials (RCTs) show that biologic
DMARDs (bDMARDs) robustly decrease disease activity,
retard radiographic progression and improve functional
outcomes in RA [1]. It is also well established that lower
socio-economic status (SES) is associated with both an
increased risk of developing RA and with poorer patient
outcomes [24]. RA patients with low SES have higher
levels of disease activity, worse physical and mental
health and reduced quality of life compared with those
with high SES [47]. Given this, SES is an important potential confounder in RA clinical trials and may impact both the
clinical outcomes and generalizability of the findings.
We reviewed the reporting of SES in 100 recent consecutive RA bDMARD RCTs published in leading general
medicine and rheumatology journals. The journals
included the New England Journal of Medicine (14
RCTs), Lancet (12), BMJ (2), Annals of the Rheumatic
Diseases (25), Arthritis and Rheumatology (25), Arthritis
Care and Research (6), Arthritis Research and Therapy
(6) and The Journal of Rheumatology (10). We extracted
data from eight journals, with 28 studies from general
medical journals and 72 studies from rheumatology journals, using methodology from a previous study [8]. Direct
measures of SES were extracted from the reported baseline demographics, including occupational group, employment status, income, educational attainment, area-based
and occupation-based SES measures and the indirect
SES measures of ethnicity, language, weight or BMI and
smoking. Publication year and location of study were recorded and used as comparative factors.
The reporting of SES characteristics of participants in
recent RA bDMARD RCTs was very limited (Table 1).
Direct SES measures of employment status, income and
educational attainment were recorded in 2, 2 and 1%,
respectively, of the published RA bDMARD trials. The remaining three direct measures of SES were not reported
in any of the trials reviewed. Ethnicity, considered to be an
indirect measure of SES, was reported in just over half of
the trials (54%), while smoking and weight/BMI were measured in 4 and 36% of the trials. The three studies that
Measures of SES
Reported
measure, %
Employment status
Income
Educational attainment
Occupational group
Area-based SES measures
Occupation-based SES measures
Ethnicitya
Languagea
Smokinga
Weight/BMIa
2
2
1
0
0
0
54
0
4
36
aSES indirect factor. SES: socioeconomic status.
reported direct measures of SES were single-country studies. More multinational studies (70%; n = 39/56) reported
at least one measure of direct or indirect SES than singlecountry studies (45%, n = 13/29). The reporting of indirect
or direct SES was not correlated with publication year or
journal.
We have demonstrated that SES was under-reported in
recent bDMARD RA clinical trials. Given the known association between low SES and disease activity and outcomes in RA, understanding the SES status of the
population included in trials is important for generalizability of the results. Additionally, indirect SES factors, such
as smoking and weight, were not reported in proportion to
their likely role in RA disease outcomes. Without adequate
reporting of SES in trial participants, the representation of
low SES is unknown. Although further research is required
to examine the relationships between SES and RA outcomes, we suggest that increased reporting of SES in RA
bDMARD clinical trials would improve the capacity of clinicians to assess the applicability of trial results in everyday
clinical practice.
Acknowledgements
H.C. was supported by a University of Queensland School
of Medicine Summer Research Scholarship and H.B. is
supported by an National Health and Medical Research
Council Translating Research into Practice Fellowship.
Funding: No specific funding was received from any
bodies in the public, commercial or not-for-profit sectors
to carry out the work described in this manuscript.
Disclosure statement: H.B. has received speaker honoraria
from Bristol-Myers Squibb, Union Chimique Belge and
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Under-reporting of socio-economic status in
randomized control trials of biologic diseasemodifying anti-rheumatic drugs in rheumatoid
arthritis
TABLE 1 Reporting on measures of socio-economic
status
Letters to the Editor
Janssen and research grant funding from UCB and AbbVie.
All other authors have declared no conflicts of interest.
Hedva Chiu1, Samantha Hollingworth2,
Mieke Van Driel1, Parker Magin3 and
Helen Benham1
Rheumatology 2017;56:661663
doi:10.1093/rheumatology/kew493
Advance Access publication 29 January 2017
Pregnancy outcomes in women with rheumatoid
arthritis ever treated with rituximab
1
School of Medicine, University of Queensland, Herston,
School of Pharmacy, University of Queensland, Brisbane,
QLD and 3Discipline of General Practice, University of
Newcastle, Callaghan, NSW, Australia
Revised version accepted 16 November 2016
Correspondence to: Helen Benham, School of Medicine,
University of Queensland, Translational Research Institute, 37
Kent Street, Woolloongabba, QLD 4012, Australia.
E-mail: h.benham@uq.edu.au
Rheumatology key message
2
1 Nam JL, Ramiro S, Gaujoux-Viala C et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the
EULAR recommendations for the management of
rheumatoid arthritis. Ann Rheum Dis 2014;73:51628.
2 Bengtsson C, Nordmark B, Klareskog L et al.
Socioeconomic status and the risk of developing
rheumatoid arthritis: results from the Swedish EIRA study.
Ann Rheum Dis 2005;64:158894.
3 Pedersen M, Jacobsen S, Klarlund M et al.
Socioeconomic status and risk of rheumatoid arthritis: a
Danish case-control study. J Rheumatol
2006;33:106974.
4 Jacobi C, Mol G, Boshuizen H et al. Impact of socioeconomic status on the course of rheumatoid arthritis and on
related use of health care services. Arthritis Rheum
2003;49:56773.
5 Molina E, Del Rincon I, Restrepo JF et al. Association of
socioeconomic status with treatment delays, disease activity, joint damage, and disability in rheumatoid arthritis.
Arthritis Care Res 2015;67:9406.
6 Jiang X, Sandberg M, Saevarsdottir S et al. Higher education is associated with a better rheumatoid arthritis
outcome concerning for pain and function but not disease
activity: results from the EIRA cohort and Swedish
rheumatology register. Arthritis Res Ther 2015;17:317.
7 Margaretten M, Barton J, Julian L et al. Socioeconomic
determinants of disability and depression in patients with
rheumatoid arthritis. Arthritis Care Res 2011;63:2406.
8 Magin P, Victoire A, Zhen XM et al. Under-reporting of
socioeconomic status of patients in stroke trials: adherence to CONSORT principles. Stroke 2013;44:29202.
Rates of live births were reassuring in women with
RA exposed to rituximab before conception.
SIR, In women with RA, information concerning the exposure risk to rituximab (RTX) during pregnancy is limited.
RTX, an mAb, can cross the placenta from the second
trimester, has a long half-life, estimated to be between
18 and 23 days, and lymphocyte depletion is variable
and possibly longstanding. Hence, the current Summary
of Product Characteristics states that women should take
contraception during RTX treatment and for 12 months
after finishing RTX treatment [1]. In this analysis, we summarize the pregnancy outcomes of women with RA
receiving RTX before or during pregnancy in the British
Society for Rheumatology Biologics Register in RA
(BSRBR-RA).
This register systematically captures information on RA
patients exposed to biologic therapy to monitor long-term
safety [2]. The North-West MultiCentre Research Ethics
Committee granted Ethical approval for the BSRBR-RA.
Patients gave informed written consent. This study did not
require additional approval or consent. Following the
report of a pregnancy, additional data are collected via a
pregnancy event proforma, including information on exposure to medications, on pregnancy outcome and on
complications/congenital malformations. We included all
patients with a reported pregnancy up to 18 December
2015 exposed to RTX at any point before pregnancy
end and divided exposure into the following three
groups: exposed within 6 months before conception, between 6 and 12 months before conception, and longer
than 12 months before conception.
A total of 32 pregnancies (including 1 twin pregnancy) in
23 women were reported (Table 1). The mean (range) age
at conception was 34 (2041) years. No women received
RTX during pregnancy. Of 27 known pregnancy outcomes, 21 (66%) were live births, 2 (6%) stillborn,
3 (9%) miscarriages and 2 (6%) terminations. The
median (range) gestational length of live births (available
for 18 pregnancies) was 38 (2942) weeks. Preterm delivery, defined as gestation <37 weeks, occurred in 4/18
(22%). Unfortunately, no data on immunoglobulin levels
or lymphocyte counts in either mothers or newborns
were recorded in the BSRBR-RA.
Ten women reported RTX exposure 6 months before conception [median (range) time of exposure was
3 (15) months], with the outcome known in 9, as follows:
6 live births, 1 stillbirth after 27 weeks (placental insufficiency), 1 miscarriage and 1 termination after 5 weeks.
Four (40%) women were receiving MTX at conception.
The woman who miscarried received MTX until
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