Risk of adrenal insufficiency in patients with polymyalgia rheumatica versus patients with rheumatoid arthritis: A cross-sectional study
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Modern Rheumatology, 00, 2022, 1–8
DOI: https://doi.org/10.1093/mr/roab091
Advance Access Publication Date: 18 January 2022
Original Article
Risk of adrenal insufficiency in patients with polymyalgia
rheumatica versus patients with rheumatoid arthritis: A
cross-sectional study
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
Akiko Kasaharaa , Takashi Kidaa , Aiko Hiranoa , Satoshi Omuraa , Hideaki Sofuea , Aki Sakashitaa ,
Tomoya Sagawaa , Mai Asanob , Michiaki Fukuib , Makoto Wadaa , Masataka Kohnoa and
Yutaka Kawahitoa,*
a
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
b
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
*Correspondence: Yutaka Kawahito; kawahity@koto.kpu-m.ac.jp; Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural
University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
ABSTRACT
Objective: To determine whether patients with polymyalgia rheumatica (PMR) are more susceptible to glucocorticoid-induced adrenal
insufficiency, one of the barriers to glucocorticoid tapering strategies, compared to patients with rheumatoid arthritis (RA).
Methods: This cross-sectional study included PMR and RA patients who underwent adrenocorticotropic hormone (ACTH) tests to assess adrenal
function. The eligibility criteria were as follows: previous use of prednisolone (PSL) ≥ 5 mg/day, use of PSL for six consecutive months before
ACTH test, and current use of PSL at 5 mg/day or less. The association between disease type (PMR vs. RA) and insufficient adrenal response
was assessed using logistic regression models.
Results: Twenty-six of 34 (76.5%) patients with PMR and 13 of 37 (35.1%) patients with RA had insufficient adrenal response. Compared to
patients with RA, patients with PMR were more likely to have insufficient adrenal response, even after adjusting for age, sex, and PSL dose
(adjusted odds ratio, 6.75; 95% confidence interval, 1.78–25.60).
Conclusion: Patients with PMR have a higher risk of glucocorticoid-induced adrenal insufficiency than patients with RA. Assessing the adrenal
function in patients with PMR will contribute to establishing a more appropriate glucocorticoid reduction strategy.
KEYWORDS: Adrenal insufficiency; adrenocorticotropic hormone test; glucocorticoid; polymyalgia rheumatica; rheumatoid arthritis
Introduction itself [21–25]. Based on these previous reports, we hypothe-
Systemic glucocorticoid therapy remains one of the main- sized that patients with PMR might be particularly susceptible
stays in treating polymyalgia rheumatica (PMR) and other to glucocorticoid-induced adrenal insufficiency, leading to
rheumatic diseases [1–3]. Since prolonged glucocorticoid use both difficulty in reducing glucocorticoid dosage and relapse.
can cause damage to various organs [4, 5], it is desirable The frequency of adrenal insufficiency in patients with
to taper off or discontinue glucocorticoids once the disease PMR on glucocorticoid therapy is reportedly 15%–49%
activity has stabilized [1, 6, 7]. Additionally, prolonged [26–28]. The prevalence of glucocorticoid-induced adrenal
glucocorticoid use suppresses the hypothalamic–pituitary– insufficiency in rheumatic diseases is influenced by the dis-
adrenal (HPA) axis, leading to subsequent adrenal atrophy ease and glucocorticoid regimen [8, 28]. Currently, it remains
and glucocorticoid-induced adrenal insufficiency [8–12]. It unclear whether patients with PMR are more prone to
also causes glucocorticoid withdrawal failure in patients with glucocorticoid-induced adrenal insufficiency than patients
rheumatic diseases—a major clinical dilemma. with other rheumatic diseases. In this study, we aimed to
Relapses are common in patients with PMR, with an evaluate whether patients with PMR are at a higher risk
incidence of 20–55% [13–15]; thus, the duration of gluco- of glucocorticoid-induced adrenal insufficiency than patients
corticoid use often prolongs beyond 2 years [16–19]. The with rheumatoid arthritis (RA).
symptoms of flare in PMR, such as myalgia and fatigue, are
similar to those of adrenal insufficiency and can thus be dif-
Methods
ficult to distinguish [20]. In addition, a decreased response
of the HPA axis in inflammatory states has been reported Study population
in patients with PMR at the initial onset, suggesting that This was a cross-sectional study using data obtained from
adrenal insufficiency is related to the development of PMR an ongoing prospective cohort study. The prospective cohort
Received 3 August 2021; Accepted 4 October 2021
© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved.
For permissions, please e-mail: journals.permissions@oup.com2 Kasahara et al.
study is being conducted at four centres in Kyoto, Japan (mg/day), and PSL dose at the ACTH test (mg/day); Model 5
since 2018 and collects data on the prevalence of adrenal included age, sex, total amount of PSL until the ACTH test
insufficiency, disease type, clinical manifestation, treatment (g), and PSL dose at the ACTH test (mg/day); and Model
strategy, medication details, and blood test data from elec- 6 included only age and sex as adjustment variables. As a
tronic medical records as well as questionnaires on quality subgroup analysis, patients with PMR were also compared
of life and adrenal insufficiency symptoms in patients with with seropositive and seronegative patients with RA. As a
rheumatic diseases undergoing adrenocorticotropic hormone sensitivity analysis, a comparison of PMR and RA was also
(ACTH) testing. The inclusion criteria were all of the follow- performed for patients with age at onset ≥ 60 years or those
ing: (1) previous use of prednisolone (PSL) ≥ 5 mg/day (2) use with an initial PSL dose of ≥ 10 mg/day. In both subgroup
of PSL for six consecutive months before ACTH test, (3) cur- and sensitivity analyses, we used logistic regression models
rent use of PSL at 5 mg/day or less without disease flares, and adjusted for the same covariates as in Model 1. In addition,
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
(4) age ≥ 20 years. Patients who had interrupted and resumed the E-value was calculated using the OR and 95% CI of the
PSL administration were also included if they met the inclu- main analysis to account for possible confounders [33]. The E-
sion criteria above. All participants underwent an ACTH test value represents the minimum strength of association on the
during cohort entry. Among the cohort participants, patients risk ratio scale that an unmeasured confounder would need
with PMR who met the 2012 EULAR/ACR provisional clas- to have both the exposure and the outcome fully attenuate
sification criteria [29] and patients with RA who met the the observed exposure–outcome association [34]. Correlation
ACR/EULAR 2010 rheumatoid arthritis classification criteria analysis was also performed to assess the association among
[30] were enrolled. 30-min cortisol levels, current PSL dose, and baseline cortisol
levels, and the results were analysed using Spearman’s rank
Data collection correlation coefficient. Data analysis was performed using R
software [35].
This study used patients’ information at the time of their
entry between August 2018 and March 2021. Data on patient
demographics, disease status of PMR or RA, previous PSL Ethical considerations
dose and duration, and other immunosuppressive drugs used This study complied with the Declaration of Helsinki and
were extracted from electronic medical records. was approved by the Ethics Committee of the Kyoto Prefec-
tural University of Medicine (ERB-C-1374). All participants
provided written informed consent before enrolment.
Adrenal function evaluation
The ACTH test (also called the short Synacthen test) was per-
formed to evaluate adrenal function. Tetracosactide acetate Results
(250 µg; Cotrosin®, Daiichi Sankyo, Inc., Japan) was admin-
Patient background
istered intravenously between 8:00 and 11:00 a.m. after 24 h
of prednisolone withdrawal; blood samples were collected at A total of 34 eligible patients with PMR and 37 eligible
baseline and 30 and 60 min thereafter. Insufficient adrenal patients with RA were included in this study (Table 1). The
response was defined as a cortisol levelRisk of adrenal insufficiency in patients with polymyalgia rheumatica versus patients with rheumatoid arthritis 3
Table 1. Baseline characteristics of the 71 patients with PMR and RA.
PMR (n = 34) RA (n = 37)
Age, years 72.5 [65.5, 80.0] 73.0 [65.0, 79.0]
Sex, female 23 (68) 27 (73)
Age at onset, years 68.0 [61.0, 74.5] 63.0 [54.8, 75.0]
Cumulative duration of PSL use, years 2.7 [1.7, 4.0] 3.3 [1.5, 6.8]
History of pulse methylprednisolone therapy 0 (0.0) 1 (2.7)
RF positive 5 (15) 22 (60)
ACPA positive 0 (0.0) 16 (43)
Concomitant use of DMARDs and biological agents 17 (50) 36 (97)
MTX 6 (18) 15 (41)
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
DMARDs other than MTXa 12 (35) 31 (84)
Biological agentsb 1 (2.9) 16 (43)
Giant cell arteritis 2 (5.9) 0 (0.0)
CRP at the ACTH test, mg/dL 0.10 [0.01, 1.77] 0.11 [0.01, 1.20]
SDAI at the ACTH test N/A 1.20 [0.01, 19.03]
Initial PSL dose, mg/day 20.0 [15.0, 20.0] 5.0 [5.0, 10.0]
PSL dose after 3 months of initial treatment, mg/day 12.0 [3.0, 27.5] 5.0 [1.0, 20.0]
PSL dose after 6 months of initial treatment, mg/day 8.5 [1.5, 20.0] 5.0 [0.5, 17.5]
Total amount of PSL after 3 months of initial treatment, g 1.2 [1.0, 1.6] 0.5 [0.5, 0.9]
Total amount of PSL after 6 months of initial treatment, g 2.2 [1.8, 2.5] 0.9 [0.8, 1.5]
Total amount of PSL until the ACTH test, g 5.7 [3.5, 8.8] 4.1 [1.7, 11.9]
PSL dose 6 months before the ACTH test, mg/day 3.0 [1.0, 10.0] 3.8 [1.0, 10.0]
PSL dose 3 months before the ACTH test, mg/day 3.0 [0.5, 5.0] 3.0 [0.5, 6.0]
PSL dose at the ACTH test, mg/day 3.0 [2.0, 4.0] 2.5 [1.5, 4.0]
Data are presented as number (%) or median [interquartile range].
RF: rheumatoid factor; ACPA: anti-cyclic citrullinated peptide antibody; DMARD: disease modified anti-rheumatic drug; MTX: methotrexate; SDAI: Sim-
plified Disease Activity Index; N/A: not applicable.
a
DMARDs other than MTX: PMR (mizoribine, tacrolimus, and bucillamine) and RA (tacrolimus, mizoribine, cyclosporine, iguratimod, sulfasalazine, and
bucillamine).
b
Biologic agents: PMR (tocilizumab) and RA (etanercept, golimumab, certolizumab, tocilizumab, abatacept, and baricitinib).
Figure 1. Results of the adrenocorticotropic hormone test for the two patient groups (PMR and RA). (a) Baseline, (b) 30 min, and (c) 60 min cortisol
levels. Comparison of adrenal function between the PMR and RA groups performed using the Mann–Whitney U test; p-values are presented above the
boxplots. Each boxplot shows the median and interquartile range, and the upper and lower whiskers represent the 90th and 10th percentiles,
respectively. Each circle represents an outlier.
for the observed OR and the lower limit of the 95% CI Subgroup analysis and sensitivity analysis
were 4.64 and 2, respectively. This indicates the strength For the subgroup and sensitivity analyses, we adjusted for
of the association between an unmeasured confounder with age, sex, initial PSL dose, and PSL dose at the ACTH test
PMR and insufficient adrenal response, which is required to (Table 4). Patients with PMR had a higher risk of insufficient
explain the observed association between PMR and insuf- adrenal response than patients with seropositive RA (adjusted
ficient adrenal response with the unmeasured confounding OR, 5.38; 95% CI, 1.24–23.30; p = .02) and seronegative RA
variable. The results of the univariate analysis (unplanned (adjusted OR, 9.77; 95% CI, 1.79–53.50; p = .008). Patients
analysis required by reviewers) are shown in Supplemen- with PMR also had insufficient adrenal response when com-
tary Table S1, available with the online version of this pared with patients with RA with age at onset ≥60 years
article. (adjusted OR, 11.40; 95% CI, 2.26–57.50; p = .003) and4 Kasahara et al.
Table 2. Baseline characteristic of PMR and RA patients with insufficient or normal adrenal response.
PMR (n = 34) RA (n = 37)
Normal Insufficient adrenal Normal Insufficient adrenal
adrenal response response adrenal response response
(n = 8) (n = 26) (n = 24) (n = 13)
Age, years 67.0 [60.0, 82.0] 75.5 [54.0, 93.0] 70.5 [63.0, 77.3] 78.0 [68.0, 83.0]
Sex, female 6 (75) 17 (65) 20 (83) 7 (54)
Cumulative duration of PSL 2.6 [2.0, 4.6] 2.7 [1.6, 3.9] 3.3 [0.9, 4.6] 3.6 [2.0, 7.5]
therapy, years
Initial PSL dose, mg/day 15.0 [15.0, 16.3] 20.0 [15.0, 25.0] 5.0 [5.0, 10.0] 10.0 [5.0, 15.0]
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
PSL dose after 3 months of initial 12.8 [10.9, 14.0] 10.5 [7.6, 16.1] 5.0 [4.1, 5.0] 5.0 [5.0, 10.0]
treatment, mg/day
PSL dose after 6 months of initial 9.0 [7.5, 9.3] 7.8 [6.0, 11.8] 4.0 [2.5, 5.0] 5.0 [5.0, 5.0]
treatment, mg/day
Total amount of PSL after 3 months 1.2 [1.0, 1.3] 1.2 [1.0, 1.6] 0.5 [0.4, 0.6] 0.7 [0.4, 0.9]
of initial treatment, g
Total amount of PSL after 6 months 2.2 [1.8, 2.3] 2.1 [1.8, 2.7] 0.9 [0.7, 1.0] 1.2 [0.9, 2.4]
of initial treatment, g
Total amount of PSL until the 4.8 [4.4, 8.4] 6.2 [3.2, 10.1] 3.2 [1.1, 15.0] 8.5 [3.9, 10.3]
ACTH test, g
PSL dose 6 months before the 2.5 [1.0, 4.0] 4.0 [2.0, 10.0] 3.0 [1.0, 10.0] 3.0 [1.0, 6.0]
ACTH test, mg/day
PSL dose 3 months before the 2.0 [0.5, 4.0] 4.0 [2.0, 6.0] 2.5 [0.5, 5.0] 3.0 [1.5, 5.0]
ACTH test, mg/day
PSL dose at the ACTH test, mg/day 2.0 [1.0, 2.1] 3.0 [2.5, 4.0] 2.5 [1.5, 3.3] 3.0 [2.0, 4.0]
Concomitant use of DMARDs and 5 (63) 12 (46) 24 (100) 12 (92)
biologic agents
CRP at the ACTH test, mg/dL 0.09 [0.04, 1.77] 0.11 [0.01, 0.98] 0.12 [0.02, 1.20] 0.03 [0.01, 0.97]
SDAI at the ACTH test N/A N/A 1.61 [0.02, 11.18] 1.01 [0.01, 19.03]
Data are presented as number (%) or median [interquartile range].
SDAI: Simplified Disease Activity Index; N/A: not applicable.
patients with an initial PSL dose ≥10 mg (adjusted OR, 7.65; that patients with PMR have inadequate cortisol secretion
95% CI, 1.43–41.00; p = .02). in response to inflammation from the onset [21–23]. Con-
sidering these findings with the results of our study, we
speculate that patients with PMR are a population that is
Steroids and adrenal function more susceptible to glucocorticoid-induced adrenal insuffi-
The relationship between 30 min cortisol levels and PSL dose ciency due to abnormalities in the HPA axis. In patients
at the ACTH test and that between 30-min cortisol levels and with PMR, we should evaluate adrenal function and indi-
baseline cortisol levels are shown in the scatter plot (Figure 2). vidualize the method of glucocorticoid reduction, such
The PSL dose at the ACTH test correlated well with 30-min as careful PSL reduction in patients with adrenal insuffi-
cortisol levels in patients with PMR, but the correlation was ciency. Alternatively, a regimen of every other day dos-
not clear in those with RA. In addition, the baseline corti- ing from initial treatment, such as that once reported
sol level correlated well with the 30-min cortisol level in both for giant cell arteritis, may be useful [36]. This study
patients with PMR and RA. did, however, not elucidate whether adrenal insufficiency
is involved in PMR relapse. Our ongoing cohort study is
prospectively investigating symptoms of adrenal insufficiency
and disease relapse after ACTH testing, which may clar-
Discussion ify whether adrenal insufficiency is a risk factor for PMR
Glucocorticoid-induced adrenal insufficiency is one of the bar- relapse.
riers to glucocorticoid tapering strategies for patients with The prevalence of adrenal insufficiency in rheumatic dis-
rheumatic diseases, and the risk of adrenal insufficiency may eases varies according to reports. In our study, the preva-
vary by disease type. In this study, we found that 76.5% lence of adrenal insufficiency in patients with PMR was
of patients with PMR and 35.1% of patients with RA had 76.5%, which was higher than previous reports (15%–
insufficient adrenal response to the ACTH test, and patients 49%) [26–28]. The prevalence of adrenal insufficiency in our
with PMR were more likely to have adrenal insufficiency even patients with RA was 35.1%, which was consistent with
after adjusting for age, sex, and PSL dose. These suggest the 39% previously reported [37]. There are several reasons
that patients with PMR have a higher risk of glucocorticoid- for the discrepancy: previous reports of PMR used lower
induced adrenal insufficiency compared to patients with RA, cut-off values for ACTH testing or included patients with
which has never been reported before. shorter cumulative duration of PSL use [26–28], both of
Dysfunction of the HPA axis may be involved in the which may have led to a lower estimate of the prevalence
pathogenesis of PMR. More specifically, it has been reported of adrenocortical insufficiency compared with the presentTable 3. Multivariate analysis of factors associated with insufficient adrenal response.
Model 1 Model 2 Model 3 Model 4 Model 5 Model 6
aOR aOR aOR aOR aOR aOR
Clinical characteristics (95% CI) p-value (95% CI) p-value (95% CI) p-value (95% CI) p-value (95% CI) p-value (95% CI) p-value
PMR against RA 6.75 .005 7.20 (2.08– .002 6.64 .002 5.706 Kasahara et al.
Table 4. Subgroup analysis and sensitivity analysis of factors associated after the start of PSL therapy [38, 39]. Therefore, we also
with insufficient adrenal response. performed sensitivity analysis by only including patients with
an age at onset ≥60 years (PMR vs. EORA) and a sub-
aOR (95% CI) p-value
group analysis by dividing RA patients into two groups
Subgroup analysis according to seropositivity (PMR vs. seronegative RA). In
PMR against seropositive RA 5.38 (1.24–23.30) .02 both analyses, PMR was associated with a higher risk of
PMR against seronegative RA 9.77 (1.79–53.50) .008
adrenal insufficiency than RA. These results suggest that con-
Sensitivity analysis
PMR against elderly onset RA 11.40 (2.26–57.50) .003 firmed patients with PMR are at a higher risk of adrenal
(age of onset ≧60 years old) insufficiency, even when compared with populations that
PMR against RA (initial dosage 7.65 (1.43–41.00) .02 have a similar initial clinical presentation and glucocorticoid
of PSL ≧10 mg/day) exposure.
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
aOR: adjusted odds ratio; Multivariate analysis: PMR, age, sex, initial
This study has some limitations. First, we included patients
dosage of PSL, and PSL dosage at the ACTH test. with a relatively longer cumulative duration of PSL use. Sec-
ond, although we determined the cut-off for adrenal insuffi-
ciency based on previous reports on primary adrenal insuffi-
study. On the other hand, previous reports of RA [37] ciency, we recognize that a clinically meaningful cut-off for
and the present study were in concordance on these mat- glucocorticoid-induced adrenal insufficiency in patients with
ters. Thus, the prevalence of adrenal insufficiency reported rheumatic diseases is not yet established. These two issues
in different studies are not simply comparable, and this study may influence the overestimation of the prevalence of adrenal
compared the risk of adrenal insufficiency between RA and insufficiency. Third, this study was conducted with only
PMR using the same inclusion criteria and the same testing patients with RA and PMR. To overcome these limitations, we
methods. are undertaking further cohort studies including patients with
While comparing the risk of adrenal insufficiency in earlier stage and patients with a variety of diseases other than
patients with RA and PMR, it was necessary to adjust for dif- RA and PMR to prospectively follow patients for subsequent
ferences in glucocorticoid regimens. Thus, we performed mul- relapse and development of symptoms of adrenal insufficiency
tivariate analysis with multiple models adjusting for various symptoms.
indices of PSL dose. As a sensitivity analysis, we also limited In conclusion, our results suggest that patients with PMR
the analysis to patients with an initial PSL dose of ≥10 mg to have a higher risk of glucocorticoid-induced adrenal insuf-
ensure that the results were unchanged. The E-values in the ficiency than patients with RA. We recommend that the
main analysis also suggested that residual confounding due to presence of adrenal insufficiency should be considered when
differences in glucocorticoid regimens or other unmeasured treating patients with PMR and adrenal function be assessed
factors was low. when tapering or discontinuing glucocorticoids. We believe
In clinical practice, the elderly onset RA (EORA) or that individualizing the tapering of glucocorticoids accord-
seronegative RA is difficult to differentiate from early stage ing to adrenal function will allow a more precise treatment
PMR, and the diagnosis often changes during follow-up strategy for PMR.
Figure 2. Relationship between 30-min cortisol levels and both PSL dose at the adrenocorticotropic hormone test and baseline cortisol levels. (a) PSL
dose at the adrenocorticotropic hormone test and (b) baseline cortisol levels. Each circle represents an individual patient with PMR, and each triangle
represents an individual patient with RA. The solid lines are the regression lines for patients with PMR, while the dashed lines are the regression lines
for RA patients. The light grey horizontal lines represent the cut-off for insufficient adrenal response (30-min cortisol levelsRisk of adrenal insufficiency in patients with polymyalgia rheumatica versus patients with rheumatoid arthritis 7
Acknowledgements [9] Joseph RM, Hunter AL, Ray DW et al. Systemic glucocorticoid
therapy and adrenal insufficiency in adults: A systematic review.
We gratefully acknowledge the work of past and present
Semin Arthritis Rheum 2016;46:133–41.
members of our laboratory. We would like to thank Editage [10] Schacke H, Docke WD, Asadullah K. Mechanisms involved in the
(www.editage.com) for English language editing. side effects of glucocorticoids. Pharmacol Ther 2002;96:23–43.
[11] Yukioka M, Komatsubara Y, Yukioka K et al. Adrenocorticotropic
hormone and dehydroepiandrosterone sulfate levels of rheumatoid
Supplementary data arthritis patients treated with glucocorticoids. Mod Rheumatol
2006;16:30–5.
Supplementary data is available at Modern Rheumatology [12] Kuroki Y, Takabayashi C, Nishiyama K et al. Adrenocorticotropic
online. hormone response to hypoglycemic stress was preserved by a single
bedtime 3-mg dose of prednisolone in patients with rheumatoid
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
arthritis. Mod Rheumatol 2004;14:291–5.
Conflict of interest [13] Kremers HM, Reinalda MS, Crowson CS et al. Relapse in a pop-
ulation based cohort of patients with polymyalgia rheumatica. J
A.K. received a speaker’s fee from Asahi Kasei Corp. T.K. Rheumatol 2005;32:65–73.
received a speaker’s fee from Ayumi Pharmaceutical Corp. [14] Hernandez-Rodriguez J, Cid MC, Lopez-Soto A et al. Treatment
M.A. received personal fees from Takeda Pharmaceutical of polymyalgia rheumatica: a systematic review. Arch Intern Med
Corp, Ltd, outside the submitted work. M.F. received research 2009;169:1839–50.
grants from Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe [15] González-Gay MA, Matteson EL, Castañeda S. Polymyalgia
Pharma Corp., and Takeda Pharmaceutical Co., Ltd. M.F. rheumatica. Lancet 2017;390:1700–12.
also received personal fees from Daiichi Sankyo Co. Ltd, [16] Mackie SL, Hensor EM, Haugeberg G et al. Can the prognosis
Mitsubishi Tanabe Pharma Corp., and Takeda Pharmaceu- of polymyalgia rheumatica be predicted at disease onset? Results
from a 5-year prospective study. Rheumatology 2010;49:716–22.
tical Co., Ltd, outside the submitted work. M.K. received
[17] Yates M, Watts RA, Swords F et al. Glucocorticoid withdrawal in
speaker fees from Asahi Kasei Corp, Ayumi Pharmaceu-
polymyalgia rheumatica: the theory versus the practice. Clin Exp
tical Corp., Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe Rheumatol 2017;35:1–2.
Pharma Corp., and Pfizer Inc. Y.K. received research grants [18] Demir H, Tanriverdi F, Ozogul N et al. Evaluation of the
from Asahi Kasei Corp., Ayumi Pharmaceutical Corp., Dai- hypothalamic-pituitary-adrenal axis in untreated patients with
ichi Sankyo Co. Ltd, and Mitsubishi Tanabe Pharma Corp. polymyalgia rheumatica and healthy controls. Scand J Rheumatol
Y.K. also received speaker fees from Asahi Kasei Corp., 2006;35:217–23.
Ayumi Pharmaceutical Corp., Daiichi Sankyo Co. Ltd, and [19] Aoki A, Kobayashi H, Yamaguchi Y. Predictors of long-term ther-
Mitsubishi Tanabe Pharma Corp. The remaining authors apy with glucocorticoid in polymyalgia rheumatica. Mod Rheuma-
declare that they have no conflicts of interest. tol 2021;31:417–20.
[20] Dejaco C, Duftner C, Cimmino MA et al. Definition of remis-
sion and relapse in polymyalgia rheumatica: data from a litera-
ture search compared with a Delphi-based expert consensus. Ann
Funding Rheum Dis 2011;70:447–53.
None declared. [21] Straub RH, Gluck T, Cutolo M et al. The adrenal steroid
status in relation to inflammatory cytokines (interleukin-6 and
tumour necrosis factor) in polymyalgia rheumatica. Rheumatology
2000;39:624–31.
References [22] Cutolo M, Straub RH. Polymyalgia rheumatica: evidence for
[1] Dejaco C, Singh YP, Perel P et al. 2015 Recommendations for a hypothalamic-pituitary-adrenal axis-driven disease. Clin Exp
the management of polymyalgia rheumatica: a European League Rheumatol 2000;18:655–8.
Against Rheumatism/American College of Rheumatology collabo- [23] Nishi H, Nishi Y, Yagita M et al. A case of transient ACTH
rative initiative. Ann Rheum Dis 2015;74:1799–807. deficiency associated with polymyalgia rheumatica. Jpn Clin Med
[2] Camellino D, Matteson EL, Buttgereit F et al. Monitoring and 2010;1:25–7.
long-term management of giant cell arteritis and polymyalgia [24] Cutolo M, Foppiani L, Minuto F. Hypothalamic-pituitary-adrenal
rheumatica. Nat Rev Rheumatol 2020;16:481–95. axis impairment in the pathogenesis of rheumatoid arthritis and
[3] Matteson EL, Buttgereit F, Dejaco C et al. Glucocorticoids for polymyalgia rheumatica. J Endocrinol Invest 2002;25:19–23.
management of polymyalgia rheumatica and giant cell arteritis. [25] Pacheco MJ, Amado JA, Lopez-Hoyos M et al. Hypothalamic-
Rheum Dis Clin North Am 2016;42:75–90, viii. pituitary-adrenocortical axis function in patients with polymyal-
[4] van der Goes MC, Jacobs JW, Bijlsma JW. The value of gluco- gia rheumatica and giant cell arteritis. Semin Arthritis Rheum
corticoid co-therapy in different rheumatic diseases—positive and 2003;32:266–72.
adverse effects. Arthritis Res Ther 2014;16:S2. [26] Borresen SW, Thorgrimsen TB, Jensen B et al. Adrenal insufficiency
[5] Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and in prednisolone-treated patients with polymyalgia rheumatica or
abuse in SLE. Rheumatology 2012;51:1145–53. giant cell arteritis-prevalence and clinical approach. Rheumatology
[6] Smolen JS, Landewe RBM, Bijlsma JWJ et al. EULAR recom- 2020;59:2764–73.
mendations for the management of rheumatoid arthritis with syn- [27] Jamilloux Y, Liozon E, Pugnet G et al. Recovery of adrenal func-
thetic and biological disease-modifying antirheumatic drugs: 2019 tion after long-term glucocorticoid therapy for giant cell arteritis:
update. Ann Rheum Dis 2020;79:685–99. a cohort study. PLoS One 2013;8:e68713.
[7] Fanouriakis A, Tziolos N, Bertsias G et al. Update omicronn the [28] Sagar R, Mackie SW, Morgan A et al. Evaluating tertiary adrenal
diagnosis and management of systemic lupus erythematosus. Ann insufficiency in rheumatology patients on long-term systemic glu-
Rheum Dis 2021;80:14–25. cocorticoid treatment. Clin Endocrinol 2021;94:361–70.
[8] Broersen LH, Pereira AM, Jorgensen JO et al. Adrenal insufficiency [29] Dasgupta B, Cimmino MA, Maradit-Kremers H et al. 2012
in corticosteroids use: systematic review and meta-analysis. J Clin provisional classification criteria for polymyalgia rheumatica:
Endocrinol Metab 2015;100:2171–80. a European League Against Rheumatism/American College8 Kasahara et al.
of Rheumatology collaborative initiative. Ann Rheum Dis [35] R Core Team. R: A Language and Environment for Statistical
2012;71:484–92. Computing. Vienna, Austria: R Foundation for Statistical Com-
[30] Aletaha D, Neogi T, Silman AJ et al. 2010 Rheumatoid arthri- puting, 2018. https://www.R-project.org/ (3 June 2021, date last
tis classification criteria: an American College of Rheumatology/ accessed).
European League Against Rheumatism collaborative initiative. [36] Hunder GG, Sheps SG, Allen GL et al. Daily and alternate-
Ann Rheum Dis 2010;69:1580–8. day corticosteroid regimens in treatment of giant cell arteritis:
[31] El-Farhan N, Pickett A, Ducroq D et al. Method-specific serum comparison in a prospective study. Ann Intern Med 1975;82:
cortisol responses to the adrenocorticotrophin test: comparison 613–8.
of gas chromatography-mass spectrometry and five automated [37] Borresen SW, Klose M, Baslund B et al. Adrenal insufficiency is
immunoassays. Clin Endocrinol 2013;78:673–80. seen in more than one-third of patients during ongoing low-dose
[32] Javorsky BR, Raff H, Carroll TB et al. New cutoffs for the bio- prednisolone treatment for rheumatoid arthritis. Eur J Endocrinol
chemical diagnosis of adrenal insufficiency after ACTH stimulation 2017;177:287–95.
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab091/6511018 by guest on 30 January 2022
using specific cortisol assays. J Endocr Soc 2021;5:bvab022. [38] Ceccato F, Roverano S, Barrionuevo A et al. The role of anti-
[33] Mathur MB, Ding P, Riddell CA et al. Web site and R package for cyclic citrullinated peptide antibodies in the differential diagnosis
computing E-values. Epidemiology 2018;29:e45–7. of elderly-onset rheumatoid arthritis and polymyalgia rheumatica.
[34] VanderWeele TJ, Ding P. Sensitivity analysis in observa- Clin Rheumatol 2006;25:854–7.
tional research: introducing the E-value. Ann Intern Med [39] Healey LA, Sheets PK. The relation of polymyalgia
2017;167:268–74. rheumatica to rheumatoid arthritis. J Rheumatol 1988;15:
750–2.You can also read
