ACR Open Rheumatology

Vol. 0, No. 0, Month 2023, pp 1–6

DOI 10.1002/acr2.11584
© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and
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BRIEF REPORT

Lowering Expectations: Glucocorticoid Tapering Among

Veterans With Rheumatoid Arthritis Achieving Low Disease
Activity on Stable Biologic Therapy
Beth I. Wallace,1 Bryant R. England,2 Joshua F. Baker,3 Jorge Rojas,4 Brian C. Sauer,5 Punyasha Roul,6
7 7 6 2 4
Gary A. Kunkel, Tawnie J. Braaten, Alison Petro, Ted R. Mikuls, and Grant W. Cannon

Objective. In the Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial, 65% of patients with rheumatoid arthritis
(RA) in low disease activity (LDA) on stable biologic therapy successfully tapered glucocorticoids. We aimed to evaluate
real-world rates of glucocorticoid tapering among similar patients in the Veterans Affairs Rheumatoid Arthritis registry.
Methods. Within a multicenter, prospective RA cohort, we used registry data and linked pharmacy claims from
2003 to 2021 to identify chronic prednisone users achieving LDA after initiating a new biologic or targeted synthetic
disease-modifying antirheumatic drug (b/tsDMARD). We defined the index date as first LDA occurring 60 to 180 days
after b/tsDMARD initiation. The primary outcome of successful tapering, assessed at day 180 after LDA, required a
30-day averaged prednisone dose both less than or equal to 5mg/day and at least 50% lower than at the index date.
The secondary outcome was discontinuation, defined as a prednisone dose of 0 mg/day at days 180 through 210.
We used univariate statistics to compare patient characteristics by fulfillment of the primary outcome.
Results. We evaluated 100 b/tsDMARD courses among 95 patients. Fifty-four courses resulted in successful
tapering; 33 resulted in discontinuation. Positive rheumatoid factor, higher erythrocyte sedimentation rate, more back-
ground DMARDs, shorter time from b/tsDMARD initiation to LDA, and higher glucocorticoid dose 30 days before LDA
were associated with greater likelihood of successful tapering.
Conclusion. In a real-world RA cohort of chronic glucocorticoid users in LDA, half successfully tapered and a third
discontinued prednisone within 6 months of initiating a new b/tsDMARD. Claims-based algorithms of glucocorticoid
tapering and discontinuation may be useful to evaluate predictors of tapering in administrative data sets.

INTRODUCTION However, mounting evidence suggests even low-dose

Up to 80% of patients with rheumatoid arthritis (RA) use
glucocorticoids, with 30% to 60% of patients using them long
term (1). RA treatment guidelines previously supported adding
glucocorticoids when initiating disease-modifying antirheumatic
drug (DMARD) therapy, or in the case of DMARD failure (2).
glucocorticoids have unacceptably toxicity when used long
term, and that difficulty tapering glucocorticoids is common
after their initiation, resulting in potentially avoidable chronic
use (3–5). In light of this, the American College of Rheumatology
(ACR) now strongly recommends against use of long-term glu-
cocorticoids when initiating DMARDs for RA and conditionally

Dr. Wallace’s work was supported by Veterans Affairs Clinical
Science Research and Development (CX002430). Dr. England’s work was sup-
ported by Veterans Affairs Clinical Science Research and Development
(CX002203). Dr. Baker’s work was supported by Veterans Affairs Clinical Sci-
ence Research and Development (CX001703) and Veterans Affairs Rehabilita-
tion Research & Development (RX003644). Dr. Mikuls’ work was supported by
a VA Merit Award (BX004600), the Department of Defense (PR200793), and
the National Institute of General Medical Sciences of the NIH (U54-GM-
115458).
1
Beth I. Wallace, MD MSc: Center for Clinical Management Research, VA
Ann Arbor Healthcare System and University of Michigan, Ann Arbor; 2Bryant
R. England, MD PhD, Ted R. Mikuls, MD MSPH: University of Nebraska Medical
Center and Veterans Affairs Nebraska-Western Iowa Health Care System,
Omaha; 3Joshua F. Baker, MD MSCE: Hospital of the University of Pennsylva-
nia and Philadelphia VA Medical Center, Philadelphia; 4Jorge Rojas, MS, Grant
W. Cannon, MD: VA Salt Lake City Healthcare System, Salt Lake City, Utah, and
VA Puget Sound Healthcare System, Seattle, Washington; 5Brian C. Sauer, PhD
MS: VA Salt Lake City Healthcare System, Salt Lake City, Utah; 6Punyasha Roul,
MS, Alison Petro, MS: University of Nebraska Medical Center, Omaha; 7Gary A.
Kunkel, MD, Tawnie J. Braaten, MD: VA Salt Lake City Healthcare System and
University of Utah, Salt Lake City.
Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.
1002/acr2.11584.
Address correspondence via email to Beth Wallace, MD, MSc, at
brennerb@umich.edu.
Submitted for publication April 27, 2023; accepted June 17, 2023.

1

2 WALLACE ET AL
SIGNIFICANCE & INNOVATIONS
• In a real-world rheumatoid arthritis population of
chronic glucocorticoid users who reach low disease
activity after starting a new biologic or targeted
synthetic disease-modifying antirheumatic drug
(b/tsDMARD), 54% successfully tapered glucocorti-
coids and 33% discontinued them within 6 months.
• Although rates of discontinuation were predictably
lower than seen in clinical trials, more than half of
new b/tsDMARD initiations in this real-world popu-
lation resulted in at least a 50% reduction in gluco-
corticoid use to less than 5 mg/day.
• Characteristics associated with a greater likelihood
of successful tapering included positive rheumatoid
factor, higher enrollment erythrocyte sedimenta-
tion rate, greater number of conventional synthetic
DMARDs at b/tsDMARD initiation, shorter time from
b/tsDMARD initiation to index date, and higher
average glucocorticoid dose over the 30 days prior
to index date.
• Prespecified claims-based algorithms for glucocor-
ticoid tapering and discontinuation may be useful
to evaluate predictors of successful tapering, yield-
ing results that are more clinically applicable than
those from a highly restricted clinical trial
population.
recommends modifying DMARDs rather than continuing gluco-
corticoids to maintain low disease activity (LDA) (6).
In 2020, Burmester et al published the Steroid EliMination In
RA (SEMIRA) trial, a large double-blind multicenter randomized
controlled trial (RCT) of glucocorticoid discontinuation in patients
with RA (7). Unlike earlier clinical trials evaluating time-limited, pro-
tocolized glucocorticoid use as a means to induce remission in
early RA, SEMIRA was the first large RCT of glucocorticoid taper-
ing to focus on patients prescribed stable doses for long-term
management of established RA (8). The SEMIRA protocol ran-
domized 259 adult participants in stable LDA on tocilizumab
and prednisone 5 mg/day to either continue prednisone for
24 weeks or taper to 0 mg/day by week 16. In the taper group,
65% of patients remained off glucocorticoids and in flare-free
LDA at week 24. However, it remains unclear how these obser-
vations compare with rates of discontinuation in real-world
patients in which greater comorbidity is observed and there is
no prespecified strategy to guide glucocorticoid tapering.
SEMIRA also did not examine whether the 35% of patients
who could not discontinue glucocorticoids could instead toler-
ate a reduced dose.
Prior observational work on this topic is limited to relatively
small international cohort studies and has produced variable
results. In a single-center Japanese cohort of 36 patients on sta-
ble RA treatment regimen that specifically included prednisolone,
58% were able to discontinue prednisolone within 1 year, but
the mean dose among persistent users did not significantly
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change (9). In a secondary analysis from the Japanese Institute
of Rheumatology, Rheumatoid Arthritis (IORRA) database,
although use and dose of glucocorticoids decreased significantly
in patients with established RA who initiated biologic DMARDs
(bDMARDs), 51% remained on glucocorticoids 2 years later (10).
In comparison, a subcohort of 97 patients with experience with
DMARDs with early RA in the Chinese Treat to TARget in RA
(TARRA) cohort had only a 23% cumulative probability of gluco-
corticoid discontinuation after 1 year (5). None of these study
populations replicated SEMIRA inclusion criteria (ie, established
RA with stable LDA on a bDMARD plus glucocorticoids) and none
examined glucocorticoid dose reduction using predefined criteria.
We aimed to evaluate real-world rates of glucocorticoid
tapering among patients enrolled in the Veterans Affairs Rheuma-
toid Arthritis (VARA) registry. Compared with the results of the
SEMIRA trial, we hypothesized that less than 65% patients would
be able to successfully discontinue glucocorticoids given higher
rates of comorbidity and less rigorous disease control in routine
practice relative to a clinical trial population, but that a roughly
equivalent number would be able to reduce their glucocorticoid
dose without complete discontinuation.
PATIENTS AND METHODS
Population and data sources. This retrospective cohort
study included participants in VARA, a longitudinal multicenter
observational cohort study of US Veterans with RA fulfilling 1987
ACR classification criteria. VARA registry data were linked to
national VA pharmacy claims data accessed through the VA
Corporate Data Warehouse, as previously described (11). All
participants provided written informed consent prior to registry enroll-
ment, and each site maintains institutional review board approval.
Registry participants were selected for analysis if they 1) initi-
ated a new single biologic or targeted synthetic DMARD
(b/tsDMARD) (6) between May 2003 and July 2021; 2) had docu-
mented LDA, defined as a disease activity score in 28 joints
(DAS-28) of less than or equal to 3.2, at least 60 but no more than
180 days after b/tsDMARD initiation; 3) remained on continuous
b/tsDMARD therapy for at least 210 days after documented
LDA; and 4) met predetermined criteria for chronic glucocorticoid
use at b/tsDMARD initiation (Figure 1). If a participant had multiple
qualifying b/tsDMARD course, each course was included sepa-
rately in the analysis.
We defined index date as the first recorded LDA between
60 and 180 days after b/tsDMARD initiation. We defined continu-
ous b/tsDMARD therapy as sequential dispensing episodes of a
single drug with no gaps of therapy longer than 90 days between
the end of one episode and the beginning of the next (11). We
operationalized chronic glucocorticoid use as 1) use of predni-
sone at least 5 mg/day on the day of b/tsDMARD initiation or
averaged over the 30 previous days; 2) use of at least 5 mg/day
prednisone at index date or averaged over the 30 days prior to

GLUCOCORTICOID TAPERING AMONG VETERANS WITH RA
Figure 1. Schematic of study design. Biologic and targeted synthetic DMARDs included abatacept, adalimumab, anakinra, certolizumab,
etanercept, golimumab, infliximab, rituximab, tocilizumab, baricitinib, upadacitinib, tofacitinib. b/tsDMARD, biologic or targeted synthetic DMARD;
DMARD, disease-modifying antirheumatic drug; GC, glucocorticoid; LDA, low disease activity.
index date; and 3) at least two prednisone dispensing episodes,
each with days’ supply of at least 28 days. To focus on continuous
rather than intermittent glucocorticoid use, we also required at least
one prednisone dispensing episode to occur in the 90 days prior to
b/tsDMARD initiation, and a second episode to occur 25 to 90 days
after the first, within the period 10 days preinitiation to 90 days post-
initiation of the b/tsDMARD. We excluded participants who received
oral or IV glucocorticoids other than prednisone between −30 and
210 days from index date, with the exception of premedication
given as part of a b/tsDMARD administration protocol.
For each prednisone dispensing episode, the prescribed
dose for each day was imputed from the following pharmacy
claims variables: dispensing episode start date, unit drug dose,
days’ supply, and quantity of tablets dispensed. In cases in which
multiple dispensing episodes covered a given day, the total daily
dose was reported as the sum of the doses from all dispensing
episodes involving that day. We calculated an average 30-day
prednisone dose as the sum of the daily prednisone doses over
a 30-day time period divided by 30.
Clinical variable assessment. As part of the VARA regis-
try, treating rheumatologists collected ACR core measures as
part of routine clinical care. These included erythrocyte sedimen-
tation rate (ESR, mm/h), C-reactive protein (CRP, mg/dl),
28-joint swollen joint count, 28-joint tender joint count, patient
and provider global assessments (0-100 mm visual analogue
scale), and multidimensional health-assessment questionnaire
(12). The aforementioned variables were used to calculate the
DAS-28 (13). Additional variables collected at enrollment were
self-reported race, sex, and smoking status (current, former,
never). Anticyclic citrullinated peptide (anti-CCP, U/ml) antibody
and rheumatoid factor (RF, IU/ml) were measured using banked
serum collected at enrollment, as previously described (14).
Linked pharmacy claims data were used to determine conven-
tional synthetic DMARD (csDMARD) and b/tsDMARD use.
Outcomes and statistical analysis. Our primary out-
come of successful glucocorticoid tapering, assessed at day
180 after index date, required both a 50% reduction in 30-day
25785745, 0, Downloaded from https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11584 by Cochrane Peru, Wiley Online Library on [27/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
3
averaged prednisone dose compared with index date, and a
30-day averaged glucocorticoid dose of less than or equal to
5 mg/day. Our secondary outcome was discontinuation, defined
as a daily prednisone dose of 0 mg/day between day 180 and
day 210. We used univariate statistics to compare patient charac-
teristics by fulfillment of the primary outcome.
RESULTS
Of 3216 VARA participants, 100 b/tsDMARD courses
among 95 patients (3%) fulfilled study eligibility criteria (Figure 1).
Characteristics of analyzed participants are summarized in
Table 1. Of these, 93% were male, 81% were white, 83% had a
history of smoking, 81% had positive RF, and 82% had positive
anti-CCP antibodies. At b/tsDMARD start, mean (SD) age and
RA duration were 64 (8.8) years and 14.4 (12.6) years, respec-
tively, and mean prednisone dose was 11.0 (10.2) mg/day. The
b/tsDMARD initiated was a tumor necrosis factor inhibitor in
62 courses (62%), tocilizumab in 15 courses (15%), abatacept
in nine courses (9%), and rituximab in nine courses (9%). Com-
mon background csDMARDs at the time of b/tsDMARD initiation
included methotrexate (40%), hydroxychloroquine (39%), sulfasa-
lazine (14%) and leflunomide (14%). Forty-six percent of partici-
pants were taking at least two csDMARDs at b/tsDMARD
initiation (Table 2).
The mean (SD) time from b/tsDMARD initiation to index date
was 130.9 (51.3) days and median (IQR) was 123 (87) days. The
mean (SD) prednisone dose at b/tsDMARD initiation, index date,
and primary outcome assessment were 11.0 (10.2) mg/day, 8.5
(8.8) mg/day, and 3.9 (4.8) mg/day, respectively. Mean
(SD) prednisone dose reduction between index date and day
180 was −4.6 (10.4) mg/day.
Of the courses fulfilling eligibility criteria, 54 (54%) met the pri-
mary outcome of successful glucocorticoid tapering. Of these
54, 33 (33% of total) also resulted in glucocorticoid discontinua-
tion. In univariate analyses, characteristics associated with a
greater likelihood of successful tapering included positive RF,
higher enrollment ESR, greater number of csDMARDs at
b/tsDMARD initiation, shorter time from b/tsDMARD initiation to
 25785745, 0, Downloaded from https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11584 by Cochrane Peru, Wiley Online Library on [27/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4 WALLACE ET AL

Table 1. Data attrition table require further validation, our results preliminarily suggest that
Patients Courses claims-based measures may be useful to classify patients by their
All VARA participants 3216 — ability to taper glucocorticoids, allowing further study of factors
≥1 b/tsDMARD course between May 1, 1875 7190 associated with taper success (16).
2003, and July 31, 2021 In our cohort, use of more background csDMARDs at
b/tsDMARD course ≥180 days duration 1644 3640
Disease activity documented 1152 2083 b/tsDMARD start was associated with successful glucocorticoid
60-180 days after b/tsDMARD start tapering, whereas glucocorticoid dose immediately prior to
LDA documented 60-180 days after 571 922 b/tsDMARD start and DAS-28 at index date were not. Similar
b/tsDMARD start
findings were observed in subgroup analyses from the
b/tsDMARD course continues through 522 650
day 210 SEMIRA trial and in DMARD-experienced patients in small inter-
≥5 mg/day prednisone equivalent 202 218 national cohorts (5,7,10). These results support the use of
either at b/tsDMARD start or
glucocorticoid-sparing DMARD treatment to achieve and main-
averaged over the 30 previous days
≥1 glucocorticoid fill ≤90 days before 164 154 tain LDA and facilitate successful glucocorticoid tapering (6). The
b/tsDMARD start and ≥1 lack of association between baseline glucocorticoid dose or
glucocorticoid fill from −10 days to DAS-28 and successful tapering is supported by previous work
+90 days after b/tsDMARD start,
occurring 25-90 days after a previous suggesting that provider preferences or noninflammatory pain
fill conditions, rather than disease activity, often drive glucocorticoid
≥5 mg/day prednisone either on date of 95 100 use in RA (3,17). The observed association between higher enroll-
LDA above, or averaged over the 30
ment ESR and successful glucocorticoid tapering may reflect
previous days
Abbreviations: b/tsDMARD, biologic or targeted synthetic disease-
confounding by age or comorbidities, especially as enrollment
modifying antirheumatic drug; LDA, low disease activity; VARA, VA CRP and DAS-28 do not show a similar relationship.
Rheumatoid Arthritis Registry. Our study reinforces the limited generalizability of traditional
clinical trials to a real-world population. Only 3% of VARA partici-
index date, and higher average glucocorticoid dose over the pants satisfied criteria for inclusion in the current study, a number
30 days prior to index date (all P ≤ 0.05). Characteristics associ- comparable to the 3% to 7% of patients with RA in clinical prac-
ated with a greater likelihood of discontinuation were similar but tice who meet criteria for trials of treatment escalation (18,19). In
also included younger age (P = 0.04). both trial types, exclusions were primarily due to missing disease
activity documentation and disease activity measurements that
exceeded trial inclusion cutoffs. These results emphasize the
need for prospective studies of chronic glucocorticoid users with
DISCUSSION
RA, both to identify potential candidates for glucocorticoid taper-
In a real-world population of chronic glucocorticoid users ing and to develop generalizable, clinically feasible tapering
who achieve LDA after initiating a new b/tsDMARD for RA, 54% guidelines.
of courses achieved a prespecified, claims-based definition of There are additional limitations to this study. As discussed
successful glucocorticoid tapering and 33% discontinued gluco- above, we included only participants who met rigorous inclusion
corticoids, within 6 months. Although rates of glucocorticoid dis- criteria, similar to those used in clinical trials of steroid tapering.
continuation in this real-world population were predictably lower This reduces the generalizability of results to the larger population
than seen in a recent clinical trial (7), the majority of patients stud- of steroid users. Although the demographics of VARA participants
ied were able to reduce their glucocorticoid use by 50% and to reflect those of the broader VA population, demographic differ-
less than or equal to 5 mg/day. ences between Veteran and civilian populations may also limit
Our study used prespecified, claims-based definitions of generalizability. Because of the small size of the data set after
both successful glucocorticoid tapering and glucocorticoid dis- applying eligibility criteria, we did not have sufficient power to per-
continuation. Rates of glucocorticoid discontinuation in our form multivariable modeling to adjust for potential confounders.
cohort were comparable with those seen in prior studies, allowing Further work is needed to evaluate whether the factors we identify
for differences in follow-up time (5,9,10). We also found that, here remain associated with successful glucocorticoid tapering in
among the 67% of patients who did not discontinue glucocorti- larger, multivariable analyses. Because VARA collects disease
coids within 6 months, an additional one in three reduced their activity measures during clinical encounters occurring as part of
average glucocorticoid dose during that time period. The out- routine clinical care, these measures were not routinely available
come of glucocorticoid tapering without discontinuation, although at the time of b/tsDMARD initiation, nor were they performed at
not well-studied previously, is a clinically relevant metric of standardized intervals during or after index date. This limited our
improved disease activity and is often used as a secondary end- ability to evaluate the persistence of glucocorticoid tapering and
point in DMARD efficacy trials (15). Although the algorithms discontinuation and how improved disease control after DMARD
 25785745, 0, Downloaded from https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11584 by Cochrane Peru, Wiley Online Library on [27/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
GLUCOCORTICOID TAPERING AMONG VETERANS WITH RA 5

Table 2. Cohort characteristics stratified by achievement of primary outcome

Overall cohort Primary outcome Primary outcome Met vs. not met
(N = 100) met (n = 54) not met (n = 46) P value
At enrollment
Male sex, n (%) 93 (93) 48 (88.8) 45 (97.8) 0.08
Years of education 13.1 (3.3) 12.9 (3.8) 13.4 (3.2) 0.46
RF positive, n (%) 81 (81) 48 (88.8) 33 (71.7) 0.02
CCP positive, n (%) 82 (82) 44 (81.4) 38 (82.6) 0.88
ESR 22.8 (19) 27.2 (20.2) 17.5 (16.1) <0.01
CRP 2.3 (5.4) 2.7 (3.8) 1.9 (3.1) 0.44
DAS-28 3.8 (1.6) 4.0 (1.7) 3.6 (1.5) 0.26
Race, n (%)
White non-Hispanic 81 (81.0) 42 (77.8) 39 (84.8) 0.58
Black non-Hispanic 12 (12.0) 7 (13.0) 5 (10.9)
Hispanic 6 (6.0) 4 (74.0) 2 (4.3)
American Indian/Pacific Islander 1 (1.0) 1 (1.9) 0 (0.0)
Smoking, n (%)
Current 26 (26.0) 11 (20.4) 15 (32.6) 0.91
Former 57 (57.0) 27 (50.0) 30 (65.2)
Never 17 (17.0) 8 (14.8) 9 (19.6)
At b/tsDMARD initiation
Age, y 64.0 (8.8) 63.0 (8.9) 65.1 (7.7) 0.23
RA duration, y 14.4 (12.6) 12.4 (11.3) 16.8 (13.8) 0.09
Mean prednisone dose past 30 days, mg/day 8.5 (6.6) 8.8 (6.8) 8.1 (6.4) 0.80
Type of b/tsDMARD initiated, n (%)
Abatacept 9 (9.0) 6 (11.1) 3 (6.5) 0.13
Anti-TNF 62 (62.0) 36 (66.7) 26 (56.6)
Rituximab 9 (9.0) 2 (3.7) 7 (15.2)
Tocilizumab 15 (15.0) 9 (16.6) 6 (13.0)
Tofacitinib 5 (5.0) 1 (1.8) 4 (8.7)
Number of csDMARDs at b/tsDMARD start, n (%)
0 25 (25) 12 (22.2) 13 (28.2) 0.04
1 39 (39) 16 (29.6) 23 (50.0)
2 29 (29) 20 (37.0) 9 (19.5)
3 7 (7) 6 (11.1) 1 (2.1)
At index date (LDA)
ESR 13.3 (13.6) 14.6 (14.0) 11.7 (12.0) 0.31
CRP 0.8 (1.5) 0.9 (2.4) 0.8 (0.9) 0.76
MDHAQ 0.8 (0.6) 0.9 (0.5) 0.7 (0.5) 0.25
DAS-28 2.3 (0.7) 2.3 (0.7) 2.3 (0.7) 0.91
Days from b/tsDMARD start to first LDA 130.9 (51.3) 122.7 (48.8) 140.5 (53.0) 0.08
Mean prednisone past 30 days, mg/day 8.0 (5.1) 9.1 (5.9) 6.7 (3.6) 0.02
At end of study period
Prednisone dose, mg/day 3.9 (4.8) 1.1 (2.9) 7.1 (4.9) <0.01
Prednisone dose reduction, mg/day −4.6 (10.4) −8.8 (11.4) 0.2 (6.2) <0.01
Note: Numbers presented are mean (SD) unless otherwise specified. Nonsignificant variables not presented included the following: year of
b/tsDMARD start and type of csDMARD at b/tsDMARD start.
Abbreviations: b/tsDMARD, biologic or targeted synthetic disease-modifying antirheumatic drug; CCP, cyclic citrullinated peptide;
CRP, C-reactive protein; csDMARD, conventional synthetic DMARD; DAS-28, disease activity score in 28 joints; ESR, erythrocyte sedimentation
rate; LDA, low disease activity; MDHAQ, multidimensional health-assessment questionnaire; RA, rheumatoid arthritis; RF, rheumatoid factor;
TNF, tumor necrosis factor.

escalation may affect the eventual success of glucocorticoid
tapering. Although our claims-based algorithms produced results
similar to prior studies, they have not been formally validated using
clinical data, eg medical record review or patient-reported sur-
veys. Like the SEMIRA trial, our study does not examine glucocor-
ticoid tapering among the 20% to 40% of patients who are able to
reach LDA without a b/tsDMARD; such patients may have even
greater success in tapering glucocorticoids than has been previ-
ously demonstrated. This analysis used both claims-based data
(drug dispensing) and data derived from the VARA registry
(demographics, seropositivity, disease activity scores, including
laboratory values, smoking status). Although prescription dis-
pensing data within the VA is universally captured for this popula-
tion, misclassification bias related to prescriptions filled in the
civilian sector is possible, though unlikely (20).
We demonstrate that, in a population of chronic glucocorti-
coid users in LDA after escalating b/tsDMARD therapy, more than
half tapered glucocorticoids by more than 50%, to a dose of less
than or equal to 5 mg/day, within 6 months. One third of these
patients were able to discontinue glucocorticoids within 6 months,
a rate consistent with that seen previously in international RA
cohorts (5,9,10) but lower than that seen in a large randomized

6 WALLACE ET AL
clinical trial (7). We used prespecified claims-based algorithms to
define glucocorticoid tapering and discontinuation. Once further
validated, such algorithms may be used to evaluate predictors of
successful tapering in additional registry-based and administra-
tive data sets, yielding results that are more clinically applicable
than those from a highly restricted clinical trial population. Future
work will validate the definitions we used to assess glucocorticoid
use and tapering, evaluate claims and registry-based predictors
of successful and unsuccessful glucocorticoid tapering, and
examine tapering success among patients with RA who reach
LDA without requiring a b/tsDMARD.
ACKNOWLEDGMENTS
The authors gratefully acknowledge all VARA investigators for con-
tributing data to the registry, and all participants for their help in improv-
ing the care of Veterans with RA.
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it critically
for important intellectual content, and all authors approved the final ver-
sion to be published. Dr. Cannon had full access to all of the data in the
study and takes responsibility for the integrity of the data and the accu-
racy of the data analysis.
Study conception and design. Wallace, England, Baker, Sauer,
Cannon.
Acquisition of data. Wallace, England, Baker, Kunkel, Braaten, Petro,
Mikuls, Cannon.
Analysis and interpretation of data. Wallace, England, Baker, Rojas,
Sauer, Roul, Cannon.
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