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EUROPEAN RESPIRATORY JOURNAL
ORIGINAL RESEARCH ARTICLE
S. DHOORIA ET AL.
High-dose (40 mg) versus low-dose (20 mg) prednisolone for
treating sarcoidosis: a randomised trial (SARCORT trial)
Sahajal Dhooria 1, Inderpaul Singh Sehgal 1, Ritesh Agarwal1, Valliappan Muthu1,
Kuruswamy Thurai Prasad1, Pooja Dogra1, Uma Debi2, Mandeep Garg2, Amanjit Bal 3,
Nalini Gupta4 and Ashutosh Nath Aggarwal1
1
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
3
Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. 4Department
of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
2
Corresponding author: Sahajal Dhooria (sahajal@gmail.com)
Shareable abstract (@ERSpublications)
High-dose (40 mg·day−1 initial dose) prednisolone was not superior to a lower dose (20 mg·day−1
initial dose) in improving outcomes or the HRQoL in sarcoidosis and was associated with similar
adverse effects. https://bit.ly/3XKZLvh
Cite this article as: Dhooria S, Sehgal IS, Agarwal R, et al. High-dose (40 mg) versus low-dose (20 mg)
prednisolone for treating sarcoidosis: a randomised trial (SARCORT trial). Eur Respir J 2023; 62:
2300198 [DOI: 10.1183/13993003.00198-2023].
Copyright ©The authors 2023.
For reproduction rights and
permissions contact
permissions@ersnet.org
Received: 2 Feb 2023
Accepted: 5 July 2023
Abstract
Background Current guidelines recommend 20–40 mg·day−1 of oral prednisolone for treating pulmonary
sarcoidosis. Whether the higher dose (40 mg·day−1) can improve outcomes remains unknown.
Methods We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised
controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary
sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day−1 initial dose) or low-dose
(20 mg·day−1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the
frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes
included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in
litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL)
scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale.
Findings We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the highdose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the
18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19
(44.2%) in the low-dose group ( p=0.75). The mean time to relapse/treatment failure was similar between
the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in
FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores
did not differ between the study groups.
Interpretation High-dose prednisolone was not superior to a lower dose in improving outcomes or the
HRQoL in sarcoidosis and was associated with similar adverse effects.
Introduction
Sarcoidosis is a systemic granulomatous disorder of unknown aetiology [1, 2]. Pulmonary sarcoidosis
manifests with lung opacities, enlarged intrathoracic lymph nodes, or both. Immunosuppressive treatment is
indicated if there is an imminent threat to life or organ function, or if symptoms significantly impair the
patient’s quality of life [3, 4].
Systemic glucocorticoids are the mainstay of sarcoidosis treatment as they potently suppress granulomatous
inflammation [5]. Most randomised controlled trials (RCTs) of glucocorticoids versus placebo (or no
treatment) have reported at least short-term improvements in clinical, radiological and lung function
parameters, especially in patients with symptomatic disease [6–12]. The initial prednisolone doses
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EUROPEAN RESPIRATORY JOURNAL
ORIGINAL RESEARCH ARTICLE | S. DHOORIA ET AL.
used in these studies ranged from 15 to 40 mg·day−1 and the treatment duration varied between 3 and
24 months [13]. The 1999 American Thoracic Society/European Respiratory Society (ERS)/World
Association of Sarcoidosis and Other Granulomatous Disorders statement suggested an initial prednisone
dose of 20–40 mg·day−1 [14]. The 2021 British Thoracic Society statement and a Delphi consensus have
also suggested the same dose range [15, 16]. In contrast, the 2021 ERS clinical practice guidelines
suggested an initial prednisone dose of 20 mg·day−1 for most patients without life-threatening disease, and
called for research on the initial glucocorticoid dosing [17].
We hypothesised that pulmonary sarcoidosis treatment with an initial daily prednisolone dose of 40 mg
would be superior to an initial dose of 20 mg·day−1 in reducing treatment failure or post-treatment relapse.
Herein, we compare the efficacy and toxicity of two glucocorticoid regimens in sarcoidosis (SARCORT trial).
Methods
Study design and participants
We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised trial at the
department of pulmonary medicine of the Postgraduate Institute of Medical Education and Research
(Chandigarh, India). The institute ethics committee approved the study protocol (INT/IEC/2017/299). The
study protocol is registered at clinicaltrials.gov (identifier NCT03265405). We obtained written informed
consent from all the participants. We included consecutive, treatment-naive subjects, if they satisfied all the
following criteria. 1) Age ⩾18 years; 2) computed tomography (CT) of the chest showing clinical and
radiological abnormalities consistent with a diagnosis of sarcoidosis; 3) presence of non-necrotic
granulomas on a tissue sample with the exclusion of alternative causes; and 4) significant symptoms,
reduced lung function, or an extrathoracic manifestation requiring treatment with low-to-medium-dose
glucocorticoids. Significant respiratory symptoms included breathlessness (score ⩾1 on the modified
Medical Research Council (mMRC) dyspnoea scale) or chronic cough (⩾8 weeks) impairing the subject’s
quality of life and not responding to antitussives. Reduced lung function was defined as an obstructive or
restrictive defect on baseline spirometry (supplementary material) [18].
We excluded subjects with any of the following. 1) Pregnancy or lactation; 2) contraindication to
prednisolone use at a 20 mg or 40 mg daily dose; 3) sarcoidosis manifestations requiring glucocorticoid
dose >20 mg·day−1 of prednisolone equivalent; 4) unwilling to participate in the study; or 5) received
glucocorticoids ( prednisolone equivalent ⩾15 mg·day−1) for >3 weeks in the preceding 2 years.
Randomisation and masking
We allocated eligible subjects in a 1:1 ratio using a computer-generated (StatsDirect, Birkenhead, UK)
randomisation sequence to receive prednisolone in either a high-dose or a low-dose regimen. We concealed
the treatment allocation in consecutively numbered sealed opaque envelopes and opened them before
randomisation. Neither the study subjects nor the investigators were blinded to the study treatment. An
individual not involved in the rest of the trial generated the randomisation sequence and allocated subjects.
Procedures
Subjects in the high-dose prednisolone group received an initial dose of 40 mg·day−1 for 4 weeks,
followed by 30, 20, 15, 10 and 5 mg·day−1 successively during the subsequent 4-week periods. The drug
was then tapered over 2 weeks using a dose of 5 mg·day−1 on alternate days (cumulative dose 3390 mg).
The low-dose prednisolone group received an initial dose of 20 mg·day−1 for 8 weeks followed by
15 mg·day−1 for 8 weeks, 10 mg·day−1 for 4 weeks and 5 mg·day−1 for 4 weeks, followed by tapering
using 5 mg·day−1 on alternate days for 2 weeks (cumulative dose 2410 mg). Prednisolone was
administered orally as a single daily morning dose to all subjects.
We recorded information on demographic and clinical characteristics, comorbid illness, symptom duration,
pathological findings in tissue samples, extrapulmonary sarcoidosis and the indications for glucocorticoid
treatment. We performed the following assessments before randomisation: blood pressure, fasting blood
glucose, dyspnoea severity rated on the mMRC scale, chest radiography, spirometry and dual-energy X-ray
absorptiometry (DXA) scan (supplementary material). The follow-up visits were scheduled at 8 and
16 weeks, and then at 6, 9, 12 and 18 months from randomisation. Changes in symptoms, dyspnoea
severity on the mMRC scale, body weight, blood pressure, plasma glucose, drug adherence and
treatment-related adverse effects were assessed at each follow-up visit. In addition, subjects underwent
chest radiography and spirometry at each visit. We enquired and examined the subjects specifically for
the adverse effects listed in the study proforma (supplementary material). Additionally, we recorded all
other adverse effects spontaneously communicated by the study subjects. A chest CT was repeated at the
6-month visit. The subjects completed the Sarcoidosis Health Questionnaire (SHQ) and Fatigue
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Assessment Scale (FAS) at baseline, 6 months and 18 months. DXA scans were repeated at 6 and
18 months. Subjects could visit the centre if they encountered any increase in respiratory or systemic
symptoms at any time during the study period of 18 months.
Spirometry was performed in a pulmonary function laboratory by trained technicians. We recorded the
forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in litres. We calculated the FEV1/
FVC ratio (supplementary material). If the ratio of FEV1/FVC was less than the lower limit of normal
(LLN) calculated using reference equations for our country, the subject was considered to have an
obstructive defect [18]. If the FEV1/FVC ratio was normal, but the FVC was less than the LLN, a
restrictive defect was diagnosed. Spirometry was considered normal if the ratio, FVC and FEV1 were all
above the respective LLN values. We also calculated the percentage predicted values for the FVC and
FEV1 using standard reference equations.
We recorded the abnormalities on the baseline chest radiograph and chest CT. We assigned the stage of
sarcoidosis according to the Scadding system [19]. Two radiologists compared the baseline chest
radiograph with the radiographs at 18 months. They graded the changes in parenchymal opacities and
intrathoracic lymph node size using a 5-point Likert scale (marked increase, some increase, no change,
some reduction and marked reduction) adapted from a previous RCT (supplementary material) [11]. Chest
CT at 6 months was scored similarly. Disagreement was resolved by discussion.
Definitions
We graded the overall treatment response using a multidimensional assessment of symptoms, chest
radiography, and spirometry (supplementary material). We categorised the response as resolution,
improvement, stabilisation or worsening using an adaptation of a previously described system
(supplementary material) [6]. We defined relapse as worsening (⩾25% increase in) symptoms of
sarcoidosis (such as cough, breathlessness or others), and one or more of the following. 1) Worsening of
lung function (>5-point reduction in FVC % pred), or 2) increase in the chest radiograph abnormalities due
to sarcoidosis after stopping prednisolone, adapted from BAUGHMAN and JUDSON [20] (supplementary
material). Extrapulmonary relapse was defined by the appearance of or an increase in extrapulmonary
symptom(s) with or without an abnormal laboratory parameter, as applicable. This included the
appearance, reappearance or increase in eye symptoms (red eye, visual complaints) with documented
ocular inflammation, skin rash consistent with sarcoidosis, hypercalcaemia, joint pains with or without
swelling in a pattern consistent with sarcoidosis, increase in alkaline phosphatase along with imaging
abnormalities of the liver, and others. If manifestations consistent with a relapse, as defined earlier,
appeared during the treatment period (i.e. the first 6 months of the study) or within 4 weeks of treatment
completion, it was termed as treatment failure. We recorded the time from randomisation to relapse or
treatment failure. Subjects with treatment failure or relapse were treated with prednisolone with or without
a second-line immunosuppressive agent (supplementary material). Subjects who missed their follow-up
were contacted by telephone. Those who had improvement or resolution of the disease at their last visit
and did not report any reappearance of sarcoidosis-related symptoms were considered not to have relapsed
for the intention-to-treat (ITT) analysis.
We recorded the participant’s health-related quality of life (HRQoL) using the SHQ and fatigue using the
FAS and calculated scores as per standard instructions (supplementary material) [21, 22]. The FAS
questionnaire comprises 10 items; all items were rated on a 5-point Likert scale (1=never to 5=always). The
response scores were summated to get a total score, which ranges from 10 to 50. FAS scores ⩾22 imply
fatigue and those ⩾35 represent severe fatigue [22]. The minimal clinically important difference (MCID) in
FAS score is 4 points [23]. SHQ is a 29-item questionnaire that assesses sarcoidosis-related HRQoL in three
domains, namely daily functioning, physical functioning and emotional functioning [21]. All questionnaire
items were rated on a 7-point Likert scale. The response scores were summated to get the three domain
scores and a total score, which ranged from 1 to 7, with higher scores reflecting better HRQoL.
We assessed the study treatment adherence by calculating the actual dose of prednisolone consumed as a
proportion of the expected cumulative dose.
Outcomes
We assessed all outcomes at 18 months unless otherwise specified (supplementary material). The primary
outcome was the proportion of subjects with a relapse of sarcoidosis or treatment failure. The secondary
outcomes included 1) the time to relapse or treatment failure; 2) overall response to treatment; 3) change in
FVC at 6 and 18 months; 4) cumulative prednisolone dose; 5) change in the sarcoidosis-related
health status and fatigue on the SHQ and FAS scales at 6 and 18 months; and 6) treatment-related adverse
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effects (TRAEs). Exploratory outcomes included the changes in dyspnoea severity, FVC (absolute and
% pred), chest radiograph findings and overall treatment response at 8 weeks, the overall response and
findings on chest CT at 6 months, and others (supplementary material).
Statistical analysis
Sample size calculation
In a study using a 20 mg·day−1 initial dose of prednisolone, a 74% incidence of relapse was observed over
4 years with 80% of the relapses (i.e. ∼60% relapse incidence) occurring in the first year after treatment
discontinuation [24]. A higher initial dose (1 mg·kg−1·day−1) of prednisolone was associated with relapse in
13% of subjects in another study [25]. Accordingly, we assumed a 60% relapse incidence in our 20 mg dose
group and 26% in the 40 mg dose group (double the rate in the study using 1 mg·kg−1 dose). Thus, a sample
size of 40 subjects in each group was required to establish a difference between the study groups (power of
80%, two-sided Type 1 error rate of 5%). We included 86 subjects (43 in each group) to compensate
for attrition.
We have presented descriptive data as mean±SD, mean±SE, median (interquartile range) or number
(percentage). We performed an ITT analysis for the primary and secondary outcomes. We performed post
hoc sensitivity analyses for the primary outcome for subgroups based on age, sex, body weight, sarcoidosis
stage, dyspnoea severity, FVC % pred and extrapulmonary involvement. In addition, we assessed the primary
and secondary outcomes after excluding subjects with normal spirometry and no lung disease on chest CT.
We have presented the mean difference (95% CI) in the outcomes between the groups. We compared
categorical variables using the Chi-squared test (or Fisher’s exact test), and continuous variables using the
Mann–Whitney U-test (or t-test). We used Cohen’s ĸ-statistic to assess the agreement between the
radiologists for rating the radiological changes. We plotted the Kaplan–Meier survival curve for the time to
relapse or treatment failure and used the log-rank test to compare this outcome between the study groups.
We used linear mixed models to analyse the change in FVC % pred, SHQ scores and FAS scores across
study visits between the study groups. Statistical significance was assumed at p3 weeks
4 disease duration >2 years
2 contraindications to high-dose prednisolone
86 met the inclusion criteria
Allocation
86 randomised
43 received high-dose prednisolone
43 received low-dose prednisolone
Analysis
Follow-up
1 discontinued
1 withdrew consent
42 completed 6-month treatment
0 discontinued
43 completed 6-month treatment
5 discontinued
5 withdrew consent
2 discontinued
2 withdrew consent
37 completed 18-month follow-up
41 completed 18-month follow-up
43 included in analysis
43 included in analysis
FIGURE 1 Consolidated Standards of Reporting Trials (CONSORT) diagram showing patient disposition.
The indications of glucocorticoid treatment in these subjects included significant and persistent respiratory
symptoms such as cough unresponsive to antitussives (n=8), articular disease unresponsive to nonsteroidal
anti-inflammatory drugs (n=5) and granulomatous hepatitis (n=2); some of these subjects had more than
one treatment indication. In the 61 subjects treated for abnormal spirometry, the mean±SD FVC was
68.8±11.0% pred and the mean±SD FEV1 was 63.3±13.1% pred. 42 (97.7%) subjects completed the
6-month treatment in the high-dose group and 43 (100%) in the low-dose group (figure 1). Approximately
97.7% and 95.3% of subjects in the high-dose and low-dose groups, respectively, had ⩾95% adherence to
the study medication.
Primary and secondary outcomes
37 (86.0%) subjects completed the 18-month follow-up in the high-dose group and 41 (95.3%) in the
low-dose group. 14.3% (six out of 42) and 9.3% (four out of 43) subjects had treatment failure in the
respective groups ( p=0.52). Seven of the eight subjects lost to follow-up could be interviewed by
telephone and did not report any reappearance of sarcoidosis-related symptoms or use of systemic
glucocorticoids. They were judged not to have relapsed for the ITT analysis; one subject who could not be
contacted was assumed to have had a relapse. Thus, we observed a relapse or treatment failure ( primary
outcome) in 20 (46.5%) out of 43 subjects in the high-dose group (table 2) and 19 (44.2%) out of 43
subjects in the low-dose group (mean difference −0.02, 95% CI −0.22–0.18; p=0.75). Assuming the
best-case scenario resulted in no absolute difference between the study groups ( p=1.00). Assuming the
worst-case scenario revealed a mean difference of −0.07 ( p=0.52). There were no differences in the relapse
incidence between the study groups in any of the subgroups analysed (figure 2). The mean time to relapse
or treatment failure (figure 3) was similar in the study groups (high-dose 307 days, low-dose 269 days;
p=0.27). All the relapsed subjects (n=38) had increased symptoms; 30 (78.9%) had an increase in chest
radiograph abnormalities; 28 (73.7%) had worsened spirometry. In two subjects, relapse occurred at an
extrapulmonary site (both subjects were in the low-dose group and had reappearance of joint disease); in
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TABLE 1 Baseline characteristics of the intention-to-treat population
Subjects
Demographic variables
Age, years
Male
Body mass index, kg·m−2
Smoking or biomass smoke exposure
Comorbid illnesses
Hypertension
Diabetes mellitus
Chronic kidney disease
Hypothyroidism
Asthma
Diagnostic basis (tissue samples showing granulomas)
Lymph node aspirate
Lung biopsy
Bronchial mucosal biopsy
Others#
Clinicoradiological
Radiological stage
Chest radiograph
0
1
2
3
4
Chest CT
Intrathoracic lymph nodes alone
Intrathoracic lymph nodes and parenchymal infiltration
Parenchymal infiltration
Signs of lung fibrosis
Duration of symptoms, months
Dyspnoea severity, mMRC scale
Spirometric abnormality
Obstructive defect
Restrictive defect
Normal
Spirometric parameters
FVC, L
FVC, % pred
FEV1, L
FEV1, % pred
Extrapulmonary organ involvement
Any
Hypercalcaemia/hypercalciuria
Liver
Eye
Skin
Joints
Others¶
High-dose
prednisolone
Low-dose
prednisolone
43
43
43.0±10.5
19 (44.2)
24.1±4.0
2 (4.7)
45.0±11.0
23 (53.5)
25.1±3.8
3 (7.0)
13 (30.2)
5 (11.6)
0
0
1 (2.3)
8 (18.6)
7 (16.3)
1 (2.3)
1 (2.3)
0
17/23 (73.9)
27/32 (84.4)
18/32 (56.3)
6/6 (100.0)
1 (2.4)
23/27 (85.2)
24/33 (72.7)
24/35 (68.6)
2/3 (66.7)
2 (4.8)
1 (2.3)
4 (9.3)
26 (60.5)
10 (23.3)
2 (4.7)
0 (0)
8 (18.6)
24 (55.8)
10 (23.3)
1 (2.3)
6 (14.0)
24 (55.8)
11 (25.6)
2 (4.7)
8.1±6.0
1 (1–2)
7 (16.3)
26 (60.5)
7 (16.3)
3 (7.0)
9.3±5.9
1 (1–2)
15 (34.9)
15 (34.9)
13 (30.2)
11 (25.6)
20 (46.5)
12 (27.9)
2.42±0.73
76.4±16.9
1.80±0.64
73.0±22.0
2.46±0.74
75.8±14.1
1.86±0.60
72.6±16.6
23 (53.5)
9 (20.9)
6 (14.0)
4 (9.3)
3 (7.0)
3 (7.0)
2 (4.7)
18 (41.9)
10 (23.3)
2 (4.7)
2 (4.7)
3 (7.0)
5 (11.6)
0
Data are presented as n, mean±SD, n (%) or median (interquartile range). CT: computed tomography; mMRC:
modified Medical Research Council; FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s.
#
: granulomatous inflammation in liver (n=5), parotid (n=1) and soft tissue swelling (n=2); ¶: parotitis and soft
tissue swelling in one patient each.
the remaining subjects, the respiratory system was the relapse site. Both the subjects with extrapulmonary
relapse had stage 1 disease on the chest radiograph and had significant joint pains before treatment
initiation. One of them also had significant persistent cough necessitating treatment. Most (71.0%) subjects
with relapse were treated with a combination of prednisolone and another immunosuppressive agent, most
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TABLE 2 Study outcomes by intention-to-treat analysis, unless otherwise stated
Subjects
Primary outcome
Relapse or treatment failure at 18 months
Secondary outcomes
Time to relapse or treatment failure, days, mean±SD
Overall treatment response at 18 months
Resolution
Improvement
Stabilisation
Worsening
Change in FVC at 6 months, L#
Change in FVC at 6 months, % pred
Change in FVC at 18 months, L¶
Change in FVC at 18 months, % pred
Cumulative dose of prednisolone, mg, mean±SD
SHQ, change in score at 6 months+
Daily functioning
Physical functioning
Emotional functioning
Total
SHQ, change in score at 18 months§
Daily functioning
Physical functioning
Emotional functioning
Total
Change in FAS score at 6 months+
Change in FAS score at 18 months§
High-dose prednisolone
Low-dose prednisolone
Mean difference (95% CI)
p-value
43
43
20 (46.5)
19 (44.2)
−0.02 (−0.22–0.18)
0.75
307±129
269±70
−38 (−106–30)
0.27
0.18
7 (16.3)
22 (51.2)
11 (25.6)
3 (7.0)
0.20±0.05
6.3±1.5
0.20±0.06
6.2±1.7
4408±1812
10 (23.3)
12 (27.9)
17 (39.5)
4 (9.3)
0.17±0.04
5.2±1.3
0.10±0.05
3.3±1.4
3562±1679
−0.03 (−0.16–0.10)
−1.1 (−4.8–2.7)
−0.10 (−0.25–0.05)
−3.0 (−7.3–1.3)
−846 (−1595– −97)
0.66
0.58
0.19
0.17
0.03
0.32±0.15
0.61±0.18
0.72±0.18
0.52±0.15
0.45±0.14
0.92±0.15
0.48±0.16
0.56±0.13
0.13 (−0.27–0.53)
0.31 (−0.14–0.76)
−0.24 (−0.70–0.22)
0.03 (−0.35–0.41)
0.53
0.18
0.31
0.87
0.61±0.12
0.97±0.18
0.94±0.18
0.78±0.16
−6.19±1.43
−7.24±1.26
0.56±0.16
1.13±0.12
0.75±0.15
0.77±0.11
−4.00±1.29
−5.40±1.15
0.04 (−0.34–0.43)
0.16 (−0.26–0.58)
−0.18 (−0.64–0.27)
−0.02 (−0.39–0.35)
2.19 (−1.57–5.96)
1.84 (−1.52–5.19)
0.82
0.46
0.43
0.92
0.25
0.28
Data are presented as n, n (%) or mean±SE, unless otherwise stated. FVC: forced vital capacity; SHQ: Sarcoidosis Health Questionnaire; FAS: Fatigue
Assessment Scale. #: spirometry data imputed for four subjects in the high-dose group and two subjects in the low-dose group; ¶: spirometry data
imputed for six subjects in the high-dose group and two subjects in the low-dose group; +: SHQ and FAS scores at 6 months imputed for one
subject in the high-dose group; §: SHQ and FAS scores at 18 months imputed for six subjects in the high-dose group and two subjects in the
low-dose group.
commonly methotrexate (supplementary table S1). The mean±SD duration of treatment after relapse until
the 18-month visit was 259±107 days.
Approximately 93% of subjects in the high-dose group and 90.7% in the low-dose group had resolution,
improvement or stabilisation of disease at 18 months (table 2). The mean increases in FVC and FVC %
pred at 6 months and 18 months were not different between the study groups. Using linear mixed models
analyses, the changes in FVC % pred (p=0.40) and the FEV1 % pred ( p=0.87) over all visits during the
study period were not different between the study groups. Among the subjects with abnormal spirometry at
baseline, the mean±SD change in FVC at 6 months was similar (0.30±0.33 L in the high-dose group and
0.20±0.28 L in the low-dose group, p=0.22). Subjects in the high-dose group had received a significantly
higher cumulative dose of prednisolone (mean difference 846 mg) at the end of 18 months. Complete case
analysis of the primary and secondary outcomes did not change the direction of effects (supplementary
table S2). The radiological response on chest CT at 6 months were also similar (supplementary table S3).
The extrapulmonary manifestations responded to the treatment in all subjects.
The mean improvement in the total SHQ score at 6 months was 0.51 in the high-dose group (table 2) and
0.56 in the low-dose group ( p=0.82). The mean improvements at 18 months were 0.79 (high-dose group)
and 0.74 (low-dose group) ( p=0.79). The mean reductions in the FAS scores at 6 months were 6.26 in the
high-dose group and 4.00 in the low-dose group (p=0.25). At 18 months, FAS scores decreased by
7.32 points (high-dose group) and 5.24 points (low-dose group) ( p=0.24). At 6 months, a reduction of
4 points (MCID) was observed in 27 (64.3%) out of 42 subjects in the high-dose group and 21 (48.8%)
out of 43 subjects in the low-dose group ( p=0.15). At 18 months, 24 (64.9%) out of 37 subjects in the
high-dose group and 21 (51.2%) out of 41 subjects in the low-dose group had a 4-point reduction in FAS
scores ( p=0.22). There was a significant improvement from the baseline in the SHQ score in all domains
and a significant reduction in the FAS score at the 6-month and 18-month visits in both the study groups
https://doi.org/10.1183/13993003.00198-2023
7
EUROPEAN RESPIRATORY JOURNAL
Age, years
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