Clinical and epidemiological research
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1
Department of Rheumatology,
Johns Hopkins University
School of Medicine, Baltimore,
Maryland, USA
2
Videncenter for Reumatologi
og Rygsygdomme,
Rigshospitalet Glostrup,
Glostrup, Denmark
3
Department of Epidemiology
and Public Health, University of
Maryland, Baltimore,
Maryland, USA
Correspondence to
Theresa R Wilhelm, Videncenter
for Reumatologi og
Rygsygdomme, Rigshospitalet
Glostrup, Nordre Ringvej 57,
Glostrup 2600, Denmark;
theresa.rita.wilhelm@regionh.dk Remission, Clinical ROT and Complete ROT, respectively.
Received 4 March 2016
Revised 17 July 2016
Accepted 24 July 2016
Published Online First
24 August 2016
To cite: Wilhelm TR,
Magder LS, Petri M. Ann
Rheum Dis 2017;76:
547–553.
EXTENDED REPORT
Remission in systemic lupus erythematosus:
durable remission is rare
Theresa R Wilhelm,1,2 Laurence S Magder,3 Michelle Petri1
ABSTRACT
Introduction Remission is the ultimate goal in
systemic lupus erythematosus (SLE). In this study, we
applied four definitions of remission agreed on by an
international collaboration (Definitions of Remission in
SLE, DORIS) to a large clinical cohort to estimate rates
and predictors of remission.
Methods We applied the DORIS definitions of Clinical
Remission, Complete Remission (requiring negative
serologies), Clinical Remission on treatment (ROT) and
Complete ROT. 2307 patients entered the cohort from
1987 to 2014 and were seen at least quarterly. Patients
not in remission at cohort entry were followed
prospectively. We used the Kaplan-Meier approach to
estimate the time to remission and the time from
remission to relapse. Cox regression was used to identify
baseline factors associated with time to remission,
adjusting for baseline disease activity and baseline
treatment.
Results The median time to remission was 8.7, 11.0,
1.8 and 3.1 years for Clinical Remission, Complete
High baseline treatment was the major predictor of a
longer time to remission, followed by high baseline
activity. The median duration of remission for all
definitions was 3 months. African-American ethnicity,
baseline low C3 and baseline haematological activity
were associated with longer time to remission for all
definitions. Baseline anti-dsDNA and baseline low C4
were associated with longer time to Complete Remission
and Complete ROT. Baseline low C4 was also negatively
associated with Clinical Remission.
Conclusions Our results provide further insights into
the frequency and duration of remission in SLE and call
attention to the major role of baseline activity and
baseline treatment in predicting remission.
INTRODUCTION
Systemic lupus erythematosus (SLE) occurs in three
different patterns: relapsing-remitting, chronically
active and remission.1 A successful outcome of
treatment for the relapsing-remitting pattern might
be reduction/prevention of flares, whereas, for the
chronic active pattern, reduction or elimination of
disease activity is the goal.
In 2010, Nossent et al analysed a multicenter
European cohort and found that early remission
predicts a better disease outcome.2 Recently, Zen
et al and Steiman et al showed that patients with
prolonged remission had a lower burden of
damage.3 4 Thus, as in rheumatoid arthritis,5 remis-
sion is the ultimate goal in SLE.
Wilhelm TR, et al. Ann Rheum Dis 2017;76:547–553. doi:10.1136/annrheumdis-2016-209489
To apply the principle of treating-to-target to
SLE, it is necessary to precisely define what remis-
sion in SLE means. Accordingly, developing defin-
ition(s) of remission in SLE became the primary
recommendation on the research agenda of the
treat-to-target international task force.6 Investigation
of remission in SLE has been ongoing for >50
years,7–11 yet no agreement on the definition of
remission has been widely accepted. There are few
reports on remission and poor agreement on cri-
teria, thus yielding varying results. Online supple-
mentary table S1 summarises selected studies from
the last 20 years investigating remission. These
studies largely agree that no signs of clinical disease
activity should be present in remission. However,
disagreement starts when it comes to the definition
of ‘no disease activity’. Early studies of remission
were imprecise in the definition of ‘asymptom-
atic’,9 ‘complete remission of clinical and labora-
tory features of disease’10 or ‘asymptomatic and
without obvious active organ involvement’.11 Later
studies applied the Systemic Lupus Disease Activity
Index (SLEDAI) as an instrument to measure activ-
ity. Barr et al and Nossent et al used the physician
global assessment (PGA) in their respective defini-
tions of remission, as the SLEDAI is less able to
detect mild degrees of disease activity.1 So far,
SLEDAI and PGA have not been used in combin-
ation to study remission.
Varying importance has been attributed to sero-
logical abnormalities. A few study definitions
required serological quiescence in addition to clin-
ical quiescence,3 12 but most accept serological
activity.1 3 4 12–15 In 1979, Gladman et al first
described a small subset of patients showing sero-
logical activity, evidenced by elevated anti-dsDNA
levels and/or hypocomplementaemia, despite clin-
ical quiescence.9 In 2012, Steiman et al showed
that patients who achieved a serologically active,
clinically quiescent period lasting for at least
2 years accrued less damage over a decade com-
pared with matched controls.16
The minimum duration of quiescence required to
fulfil the definition of remission has varied. Some
studies have chosen a time criterion of 5 years in
line with oncological remission criteria. Other
common minimal durations are 1 and 2 years.
Different studies have shown quite consistent
results for the 1 year remission rates, with ranges
between 18.9% and 28.4% if serological activity
was allowed.1 2 12 13 15 In one study where sero-
logical activity was not allowed, the 1 year remis-
sion rate was just 6.5%.12 The 2, 3 and 5 years
remission rates were generally much lower, with
547
 Clinical and epidemiological research
the 5 years rates between 1.7% and 2.4%.4 12 An exception was
Zen et al’s recent study with far higher 5 years remission rates.3
Another important aspect of the definition of remission is
whether remission requires withdrawal of all treatments.
Whereas older studies did not allow any treatment, more recent
ones permit treatment with antimalarials.
A very important, but yet poorly studied group of patients in
studies of remission are those who are asymptomatic but requir-
ing corticosteroids and/or immunosuppressives. In 2014,
Steiman et al suggested that the group of patients achieving
remission under coverage of treatment with corticosteroids and/
or immunosuppressives may consist of one subset in whom
medication can be tapered and withdrawn (thus being in true
remission) and another subset in whom disease was merely
suppressed.4
Besides studying the frequency of remission and its duration,
an issue of great interest is what characterises patients who
achieve remission (see online supplementary table S1). So far,
few studies have investigated predictors of remission and
reported significant differences between the patients who
experienced remission and the ones who did not.2–4 12 15 Zen
et al’s recent study identified glomerulonephritis, vasculitis and
haematological manifestations to be negative predictors of
remission in multivariable models.3
Differences in the cohorts may play an essential role in
explaining the varying results. Ethnicity has been proven to
have an effect on disease manifestations, severity and prognosis
of SLE.17 Nevertheless, not all papers give the information on
the ethnic groups in their cohorts.
In this study, we used the definitions of remission agreed on
by a large multiparty international collaboration from the
DORIS (Definitions Of Remission In SLE) working group that
aims to find consensus definitions of remission in SLE (van
Vollenhoven RF, Aranow C, Bertsias G, et al. Remission in SLE,
consensus findings from a large international task force on defi-
nitions of remission in SLE (DORIS). submitted).18 Applying
these definitions to a large, closely monitored clinical cohort,
this study aimed to determine the time to remission, the dur-
ation of remission and the predictors of remission in SLE.
METHODS
Four different definitions have been considered: Clinical
Remission, Complete Remission, Clinical ROT and Complete
ROT, where ROT stands for remission on treatment (table 1).
To fulfil any of these definitions, the clinical SLEDAI
(cSLEDAI), meaning without serology, has to be 0 and the
PGA<0.5 on a 0–3 visual analogue scale. Prednisone is not
Table 1 DORIS definitions of remission
Clinical
Clinical Complete Remission
Remission Remission on treatment
cSLEDAI=0 ✓ ✓ ✓ ✓
PGA<0.5 ✓ ✓ ✓ ✓
Prednisone 0 0 ≤5 mg/day
Immunosuppressives None None Allowed
Serology negative × Yes × Yes
Serology includes anti-dsDNA and complement (C3, C4).
cSLEDAI, clinical SLEDAI; DORIS, Definitions Of Remission In SLE; PGA, physician global
assessment; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Disease Activity
Index.
548
Ann Rheum Dis: first published as 10.1136/annrheumdis-2016-209489 on 24 August 2016. Downloaded from http://ard.bmj.com/ on 24 April 2018 by guest. Protected by copyright.
allowed for a patient to be considered in Remission. The daily
dose of prednisone has to be ≤5 mg to be considered in ROT.
Immunosuppressive drugs are not allowed for remission, but
they are allowed for ROT. What distinguishes Clinical and
Complete Remission and ROT is the serology. Clinical
Remission and ROT are regardless of serology, whereas
Complete Remission and Complete ROT also require negative
anti-dsDNA and normal complement. Hydroxychloroquine is
allowed for both Remission and ROT.
We applied four DORIS definitions of remission to the
Hopkins Lupus Cohort, which is approved on an annual basis
by the Johns Hopkins Institutional Review Board. Patients gave
informed consent before taking part in the cohort. A total of
2307 patients were included in our analyses. Patients entered
the cohort from 1987 to 2014. Patients were seen quarterly, or
more often if warranted. At each clinic visit a large amount of
clinical information was collected, including information on
SLE disease activity and relevant serologies (anti-dsDNA via
Crithidia, complement).
In this analysis, for each of the four definitions of remission,
we considered the experience of patients who did not satisfy
that definition at baseline, defined as cohort entry. These
patients were followed prospectively until either they satisfied
that definition, they had a gap of nine or more months in their
follow-up or they dropped out of the study. For 89% of con-
secutive visits, the time between visits was <4 months. The time
to remission was ascribed to the first clinic visit in which the
specific definition of remission was satisfied.
We used the Kaplan-Meier approach to estimate the distribu-
tion of time to remission after cohort entry censoring patients
who had a gap in their follow-up or dropped out before satisfy-
ing the definition of remission. We stratified by baseline disease
activity (low activity: PGA<1 and SLEDAI<3) and baseline
treatment (low treatment: prednisone <5 mg/day, no use of
immunosuppressive drugs). Once remission was achieved,
patients were followed prospectively until relapse occurred. The
Kaplan-Meier approach was used to estimate the distribution of
time from remission to relapse. Finally, Cox regression was used
to identify patient characteristics at baseline that were associated
with time to remission, adjusting for baseline disease activity
and baseline treatment. Using this approach, we examined
demographic and immunological characteristics as well as spe-
cific types of disease activity, one variable at a time. Those vari-
ables found significantly associated with remission were then
entered into multivariable models and those that remained sig-
nificant were retained in the final models.
RESULTS
Patient characteristics
Table 2 shows the demographic and clinical characteristics of
the patients included in the analysis for each definition. In
general, 92% were female, and most were either Caucasian
Complete American or African-American. There was a wide age span from
Remission on <30 to >60. Many (39%) had been diagnosed with SLE within
treatment the last year, but 35% had SLE for five or more years.
Time to remission
≤5 mg/day
Table 3 shows the median time to remission for all the defini-
tions, overall and stratified by baseline disease activity and base-
Allowed
line treatment. We found that baseline disease activity and
baseline treatment were strongly associated with time to remis-
sion. Patients with low baseline activity (PGA<1 and
SLEDAI<3) and low treatment ( prednisone <5 mg/day, no use
of immunosuppressive drugs) achieved remission faster than
Wilhelm TR, et al. Ann Rheum Dis 2017;76:547–553. doi:10.1136/annrheumdis-2016-209489
 Clinical and epidemiological research

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Table 2 Clinical and demographic characteristics of the patients in the Hopkins lupus cohort who were not in remission at baseline, by each of
the four definitions
Not in Clinical Remission at Not in Complete Remission at Not in Clinical ‘ROT’ at Not in Complete ROT at
Patient characteristic cohort entry (n=1743) cohort entry (n=1833) cohort entry (n=1657) cohort entry (n=1787)
Sex
Female 1606 (92%) 1694 (92%) 1527 (92%) 1652 (92%)
Male 137 (8%) 139 (8%) 130 (8%) 135 (8%)
Race
Black 725 (42%) 748 (41%) 706 (43%) 741 (41%)
White 890 (51%) 949 (52%) 836 (50%) 916 (51%)
Other 128 (7%) 136 (7%) 115 (7%) 130 (7%)
Age
<30 592 (34%) 624 (34%) 562 (34%) 605 (34%)
30–39 489 (28%) 522 (28%) 470 (28%) 513 (29%)
40–49 358 (21%) 374 (20%) 343 (21%) 369 (21%)
50–59 216 (12%) 222 (12%) 204 (12%) 215 (12%)
>60 88 (5%) 91 (5%) 78 (5%) 85 (5%)
Duration of SLE prior to cohort entry (years)
<1 678 (39%) 709 (39%) 656 (40%) 698 (39%)
1–5 450 (26%) 481 (26%) 424 (26%) 462 (26%)
>5 613 (35%) 641 (35%) 575 (35%) 625 (35%)
Prednisone
<10 mg/day 966 (55%) 1056 (58%) 880 (53%) 1010 (57%)
>10 mg/day 777 (45%) 777 (42%) 777 (47%) 777 (43%)
Plaquenil
No 934 (54%) 987 (54%) 890 (54%) 960 (54%)
Yes 809 (46%) 846 (46%) 767 (46%) 827 (46%)
Use of other immunosuppressants
No 1345 (77%) 1435 (78%) 1295 (78%) 1413 (79%)
Yes 398 (23%) 398 (22%) 362 (22%) 827 (46%)
Low C3
No 1243 (75%) 1303 (74%) 1189 (54%) 1262 (74%)
Yes 424 (25%) 452 (26%) 402 (25%) 447 (26%)
Low C4
No 1349 (81%) 1407 (80%) 1283 (81%) 1363 (80%)
Yes 316 (19%) 346 (20%) 297 (19%) 344 (20%)
Anti-dsDNA
No 1097 (66%) 1125 (64%) 1036 (65%) 1083 (63%)
Yes 569 (34%) 627 (36%) 549 (35%) 626 (37%)
PGA
0–0.49 335 (19%) 425 (23%) 249 (15%) 379 (21%)
0.59–1.49 855 (49%) 855 (47%) 855 (52%) 855 (48%)
>1.5 553 (32%) 553 (30%) 553 (33%) 553 (31%)
cSLEDAI
0 715 (41%) 805 (44%) 629 (38%) 360 (21%)
1–3 388 (22%) 388 (21%) 388 (23%) 487 (28%)
>4 640 (37%) 640 (35%) 640 (39%) 900 (52%)
Baseline musculoskeletal activity
Absent 1494 (86%) 1584 (86%) 1408 (85%) 1538 (86%)
Present 249 (14%) 249 (14%) 249 (15%) 249 (14%)
Baseline cutaneous activity
Absent 1283 (74%) 1373 (75%) 1197 (72%) 1327 (74%)
Present 460 (26%) 460 (25%) 460 (28%) 460 (26%)
Baseline renal activity
Absent 1422 (82%) 1512 (82%) 1336 (81%) 1466 (82%)
Present 321 (18%) 321 (18%) 321 (19%) 321 (18%)

Continued

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Table 2 Continued
Not in Clinical Remission at Not in Complete Remission at Not in Clinical ‘ROT’ at Not in Complete ROT at
Patient characteristic cohort entry (n=1743) cohort entry (n=1833) cohort entry (n=1657) cohort entry (n=1787)
Baseline haematological activity
Absent 1574 (90%) 1664 (91%) 1488 (90%) 1618 (91%)
Present 169 (10%) 169 (9%) 169 (10%) 169 (9%)
Baseline other activity (Cons, Sero, Neuro, Vasc)
Absent 1583 (91%) 1673 (91%) 1497 (90%) 1627 (91%)
Present 160 (9%) 160 (9%) 160 (10%) 160 (9%)
Risk group
High activity, High treatment 616 (35%) 683 (37%) 616 (37%) 683 (38%)
High activity, Low treatment 468 (27%) 546 (30%) 468 (28%) 546 (31%)
Low activity, High treatment 359 (21%) 292 (16%) 323 (19%) 268 (15%)
Low activity, Low treatment 300 (17%) 312 (17%) 250 (15%) 290 (16%)
Low activity was defined as PGA<1 and SLEDAI<3. If the activity was not low, we called it high. Low treatment was defined as prednisone ≤5 mg/day and no use of immunosuppressive
drugs. If the treatment was not low, we called it high.
cSLEDAI, clinical SLEDAI; PGA, physician global assessment; ROT, remission on treatment; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Disease Activity Index.

Table 3 Median time (years) until remission for each definition and by baseline disease activity and baseline treatment strata
All High activity high High activity low Low activity high Low activity low
Definition (years) treatment treatment treatment treatment
Clinical Remission 8.7 15.0 3.3 10.5 1.4
Complete Remission 11.0 >16.0 6.0 >16.0 1.5
Clinical Remission on treatment 1.8 3.0 1.5 1.6 0.8
Complete Remission on treatment 3.1 5.6 2.7 2.1 1.0

Low activity was defined as PGA<1 and SLEDAI<3. If the activity was not low, we called it high. Low treatment was defined as prednisone ≤5 mg/day and no use of immunosuppressive
drugs. If the treatment was not low, we called it high.
PGA, physician global assessment; SLEDAI, Systemic Lupus Disease Activity Index.

those with high disease activity and high treatment. High treat-
ment was the major predictor of a longer time to remission, fol-
lowed by high activity. These finding are further illustrated in
figure 1, which shows the Kaplan-Meier curves for time to
remission overall and in subgroups defined by baseline treatment
and disease activity levels. By 1 year after cohort entry, for
example, the probability of achieving Clinical Remission was
only 3% for patients with high disease activity and high treat-
ment, but it was 42% for patients with low disease activity and
low treatment.
Duration of remission
We found the median duration of remission to be about
3 months. This was quite similar for all definitions with a
median duration of 105, 101, 109 and 101 days for Clinical
Remission, Complete Remission, Clinical ROT and Complete
ROT, respectively. This reflected the fact that most patients were
seen quarterly. Based on Kaplan-Meier estimates (curves not
shown), we determined the durability of remission by specified
times as shown in table 4. At 1 year, for example, only 13.2%
who entered Clinical Remission were still in it. At 5 years time,
only 1.2% of the patients were still in Clinical Remission and at
10 years only 0.4%.
Predictors of remission
Table 5 shows characteristics of patients at cohort entry that
were independently associated with time until remission based
on multivariable Cox regression models. We found that
African-American ethnicity and low C3 levels at baseline were
associated with lower rates of remission for all four definitions.
Baseline anti-dsDNA and baseline low C4 levels were associated
with lower rates of Complete Remission and Complete ROT.
Baseline low C4 levels were also negatively associated with
Clinical Remission. The only clinical manifestation that was
related to longer time to remission was haematological disease
activity. Other clinical manifestations (musculoskeletal, cutane-
ous and renal disease activity) were not significantly associated
with longer time to remission.
DISCUSSION
In this study, we applied four different definitions of remission
agreed on by an international collaboration from the DORIS
working group to a large cohort of patients with SLE. We deter-
mined time to remission, durability of remission and predictors
of remission. As one might expect, it was easier to reach ROT
than Remission. Baseline treatment and baseline disease activity
were strongly associated with the time to remission for all defi-
nitions. We found that the durability of remission was very
short, regardless of definition. African-American ethnicity, base-
line low C3 and baseline haematological activity were associated
with a longer time to remission. Baseline anti-dsDNA and base-
line low C4 were negative predictors for Complete Remission
and for Complete ROT. Baseline low C4 was also a negative
predictor for Clinical Remission. Our results provide further
insights into the frequency and durability of remission in SLE
and call attention to the major role of baseline activity and base-
line treatment in predicting remission.
Our results concerning durability of remission show the
relapsing-remitting nature of SLE. The median duration of
remission was only about 3 months for all definitions. This was

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Figure 1 Kaplan-Meier curves with time to remission for unstratified and stratified data. The y-axis shows the probability of continuously not being
in remission. The x-axis shows the time in days. Low activity was defined as physician global assessment <1 and Systemic Lupus Disease Activity
Index <3. If the activity was not low, we called it high. Low treatment was defined as prednisone ≤5 mg/day and no use of immunosuppressive
drugs. If the treatment was not low, we called it high. All patients are shown in blue. Patients with high systemic lupus erythematosus (SLE) activity
and high treatment are shown in red. Patients with high SLE activity and low treatment are shown in green. Patients with low SLE activity and high
treatment are shown in brown. Patients with low SLE activity and low treatment are shown in violet. ROT, remission on treatment.

Table 4 Per cent of patients still in remission, by time since start of remission
Duration Clinical Remission (n=553) Complete Remission (n=485) Clinical Remission on treatment (n=907) Complete Remission on treatment (n=800)
120 days 43.8 41.0 44.5 40.3
240 days 24.3 21.3 22.7 18.6
1 year 13.2 12.1 13.4 9.3
2 years 5.6 5.2 5.6 3.6
5 years 1.2 2.0 0.6 0.7
10 years 0.4 1.3 0.3 0.7

Patients not in remission at cohort entry were followed prospectively until either they achieved remission, they had a gap of nine or more months in their follow-up, or they dropped out
of the study.

Table 5 Baseline variables independently associated with delayed remission based on multivariable Cox models controlling for baseline levels of
disease activity and treatments
Variables Clinical Remission* Complete Remission* Clinical Remission on treatment* Complete Remission on treatment*
African-American 0.6 (0.5, 0.7) 0.6 (0.5, 0.7) 0.6 (0.5, 0.7) 0.7 (0.6, 0.8)
p<0.0001 p<0.0001 p<0.0001 p<0.0001
Baseline low C3 0.6 (0.4, 0.7) 0.4 (0.4, 0.6) 0.6 (0.4, 0.7) 0.4 (0.4, 0.6)
p=0.0019 p<0.0001 p<0.0001 p<0.0001
Baseline low C4 0.7 (0.5, 0.9) 0.4 (0.3, 0.6) 0.5 (0.4, 0.6)
p=0.015 p<0.0001 p<0.0001
Baseline anti-dsDNA 0.7 (0.6, 0.9) 0.6 (0.5, 0.7)
p=0.0019 p<0.0001
Baseline haematological activity 0.6 (0.4, 0.8) 0.6 (0.4, 0.8) 0.6 (0.4, 0.8) 0.5 (0.4, 0.7)
p=0.0002 p=0.0002 p=0.0003 p<0.0001
*Values in the table are remission rate ratios (95% CIs) and p values. Other variables not significantly predictive of remission included sex, age, musculoskeletal disease activity,
cutaneous disease activity and renal disease activity.

the time to the next quarterly cohort visit. Even though achiev-
ing remission was frequent, durable remission was rare. Notably,
even though the time to remission was very variable among the
four different definitions, the median duration of remission was
Wilhelm TR, et al. Ann Rheum Dis 2017;76:547–553. doi:10.1136/annrheumdis-2016-209489
very similar, thus underlining the need for further treatment
options to reach sustained remission.
Looking at the previous studies on remission (see online
supplementary table S1), one clearly sees how the duration of
551
 Clinical and epidemiological research
remission varies according to the minimal time criterion set in
the definition. Omitting an arbitrary time criterion in the defini-
tions of remission used in this study, though, allowed us to
better approximate the true nature of remission in SLE, which is
of a rather short duration. In other chronic inflammatory dis-
eases, such as Rheumatoid Arthritis and Crohn’s disease, the
definitions of remission do not include a time criterion.19 20
Nevertheless, it can be argued that remission needs to be a
durable state to be considered a desirable treatment outcome. In
childhood SLE, the preliminary definition of remission agreed
on by an international collaboration required a duration of at
least 6 months.21
Very few studies have obtained data on patients who achieve
remission while taking medications other than hydroxychloro-
quine. Their results, though, are in good agreement with our
findings that only few patients maintain durable remission. At
1 year, 13.4% and 9.3% of patients in our cohort were still in
clinical and Complete ROT, respectively. Our data further shows
that 0.6% and 0.7% of patients had a clinical and Complete
ROT, respectively, that lasted 5 years. In Steiman et al’s study
from 2014, 2.1% of the patients achieved remission when
defined with a minimal durability of 5 years and all medications
allowed.4 Urowitz et al observed 18.9% of patients to go into
remission for at least 1 year and 1.8% of patients to achieve
remission of at least a 5-year duration when all medications
were allowed.12 The slightly higher remission frequencies in
these studies may be explained by the allowance of corticoster-
oid at unlimited dose. Notably, in Zen et al’s purely
Caucasian cohort, considerably higher remission frequencies
were found.3 About 15.6% of patients had a 5-year remission
with corticosteroids up to 5 mg/day and all other treatments
allowed.
The question whether the definition of remission should
include patients on treatment is a controversy, as prednisone,
immunosuppressives and biologicals can cause damage.
Corticosteroids are widely used in the management of SLE,
but the price patients pay for reliance on prednisone is high.
Above 6 mg/day, the risk of later organ damage increases by
50%,22 but even lower doses may have serious side effects
including osteoporosis, hyperglycaemia, Cushing syndrome
and increased risk of infections.23 Doses above 20 mg/day lead
to a fivefold increase in the rate of cardiovascular events after
adjustment for age.24 It is not possible to decide which patients
on medication would continue in remission when reducing/
omitting medications, and in which patients disease activity is
just suppressed. Having the treat-to-target approach in mind, it
is still of great interest to know which patient characteristics
may predict if a patient has a high or low likelihood of going
into remission.
Not surprisingly, we found that the level of baseline treatment
and baseline disease activity were strongly associated with the
time to remission for all definitions. In accordance with this,
Steiman et al found that when comparing patients who achieved
prolonged remission (≥5 years) to matched and unmatched con-
trols, the former had lower disease activity measured in
SLEDAI-2K at various time points of their disease course.4
Nossent et al described that patients who experienced remission
had lower corticosteroid doses in the first year after cohort entry.2
Steiman et al also found patients who achieved prolonged remis-
sion to have lower prednisone and immunosuppressive drug use
and a lower cumulative prednisone dose than controls (measured
at the start of their remission period).4 We found that when
pooling all patients together, the time to remission depended on
the case mix. Thus, these findings are of great importance when
552 Wilhelm TR, et al. Ann Rheum Dis 2017;76:547–553. doi:10.1136/annrheumdis-2016-209489
Ann Rheum Dis: first published as 10.1136/annrheumdis-2016-209489 on 24 August 2016. Downloaded from http://ard.bmj.com/ on 24 April 2018 by guest. Protected by copyright.
the results on remission frequency and on time to remission in
different cohorts are compared, or in clinical trials.
Our study identified predictors of remission in multivariable
models. In our cohort, African-American ethnicity was asso-
ciated with lower rates of Remission and ROT. Socioeconomic
factors such as family income and education, however, were not
significant after adjusting for ethnicity. Conversely to our
results, Steiman et al did find no association between the pres-
ence of remission and race in a logistic regression model includ-
ing all potential risk factors.4 They found, however, when
comparing patients who achieved prolonged remission
(≥5 years) to matched controls, that there were significantly
more Caucasian cases among the remission group. Low levels of
serum C3 and C4 are part of the Systemic Lupus International
Collaborating Clinics (SLICC) classification criteria,25 but on
their own show low sensitivity and specificity to predict disease
flare.26 Our results show that baseline hypocomplementaemia is
associated with a decreased likelihood of achieving any defin-
ition of remission. In accordance with Zen et al’s results,3 we
identified haematological activity to be associated with a
decreased likelihood of achieving remission. Urowitz et al com-
pared a non-remission group to both a 1-year and a 5-year
remission group and found anti-dsDNA antibodies were signifi-
cantly more frequent in the non-remission group.12 We showed
that anti-dsDNA at baseline predict against achieving Complete
Remission and Complete ROT.
This was one of the largest cohort studies of remission in SLE,
and the only cohort study in which patients were followed quar-
terly by protocol. The cohort represented the epidemiology of
SLE regarding its sex distribution and is composed of a broad
variety of incomes and educational levels. As patients in this
cohort were seen at intervals of 3 months or more regularly and
patients with a gap of >9 months were excluded from the ana-
lysis, the likelihood of detecting remission was high. However,
there were some limitations of our study setting. It was a single-
centre cohort, thus the remission parameters (frequency, time to
remission and duration) reflected the patients coming to one
centre and the treatment strategies used there in the last 30 years.
Even though the cohort presented considerable ethnic variation,
it lacked large numbers of patients with Asian and Latin
American background. Further multicenter studies with different
ethnic compositions would be desirable to generalise the results.
Remission is an emerging concept in SLE. Testing definitions
of remission is of great relevance for clinical practice, as much
as for clinical trials. Our future goal is to find out which defini-
tions are most successful in predicting the best possible outcome
for our patients.
Contributors TRW contributed to the design of the work, to the analysis and
the interpretation of the data and she drafted the work. LSM contributed to the
design of the work, developed statistical tools, analysed and interpreted the data
and critically revised the manuscript. MP designed the work, acquired the data,
interpreted the data and critically revised the manuscript. All the authors
approved the final version of the manuscript and gave their agreement to be
accountable for all aspects of the work in ensuring that questions related to the
accuracy or integrity of any part of the work are appropriately investigated and
resolved.
Funding The Hopkins Lupus Cohort was funded by the US National Institutes of
Health: R0-1 AR 43727.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Patients gave informed consents before taking part in the Lupus
Hopkins Cohort. The Hopkins Lupus Cohort is approved on an annual basis by the
Johns Hopkins Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.

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