Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Most
randomized controlled trials (RCTs) in systemic lupus erythematosus (SLE)
include stratification factors to ensure a balanced allocation of subgroups
that might respond differently to therapeutic interventions. Strata could
include baseline disease activity, baseline corticosteroid dosage, or race.
Despite such stratification, geographic differences have influenced responses
in some studies. Sifalimumab and anifrolumab, fully human, IgG1 κ
monoclonal antibodies, have each been investigated in Phase II studies in SLE
(NCT01283139 and NCT01438489). Sifalimumab binds to and neutralizes the
majority of IFN-α subtypes, while anifrolumab binds to the type I IFN receptor
and thus prevents signaling by any of the type I IFNs. This study analyzed
potentially impactful differences in baseline characteristics between
geographic regions.
Methods: This
post-hoc analysis first combined data from the two studies and then
compared the baseline characteristics of the region with an expected high placebo
plus standard of care response rate (Region 1 [R1]: Central America, South
America, Eastern Europe, Asia) to those of the region with an expected low
placebo plus standard of care response rate (Region 2 [R2]: North America,
Western Europe, South Africa). Eligibility criteria, similar for the two studies,
resulted in the enrollment of patients with moderate to severe SLE with
inadequate responses to standard of care. Patients with severely active lupus
nephritis or severe neuropsychiatric SLE were excluded.
Results: Of
the 736 randomized and dosed patients, 68.9% were from R1, and 31.1% were from
R2. There were no significant baseline differences between regions in mean SLEDAI-2K,
BILAG 2004 composite, or Physician’s Global Assessment scores. However,
differences were seen in other clinical characteristics as well as demographic and
background medication use (table).
Conclusion: SLE
patients enrolled in RCTs from different geographic regions had notable
differences in some demographic and baseline clinical characteristics as well
as in standard of care medications. These differences may impact the analysis
of the treatment response to standard of care and/or investigational drug.
Therefore, the possibility of an imbalance in patients recruited from regions
with expected high or low standard of care response should be considered in the
design of SLE RCTs.
|
Demographics, Clinical Characteristics, and Standard of Care Medications
|
|||
|
|
Region 1 (N=507) |
Region 2 (N=229) |
P-value
|
|
Age, years, mean (SD) |
38.0 (11.8) |
43.0 (11.4) |
<0.001 |
|
Body mass index, kg/m2, mean (SD) |
25.2 (5.0) |
28.1 (7.3) |
<0.001 |
|
Disease duration, months, mean (SD) |
81.8 (75.8) |
131.2 (92.4) |
<0.001 |
|
SLICC/ACR Damage Index, mean (SD) |
0.5 (0.9) |
1.1 (1.5) |
<0.001 |
|
Double-stranded DNA antibodies, % |
85.0 |
67.3 |
<0.001 |
|
Hypocomplementemia, % |
|
|
|
|
C3 |
44.8 |
33.6 |
0.005 |
|
C4 |
29.0 |
18.3 |
0.002 |
|
Background medications, % |
|
|
|
|
Azathioprine |
28.8 |
12.2 |
<0.001 |
|
Mycophenolate |
5.1 |
21.0 |
<0.001 |
|
Corticosteroids |
94.1 |
65.1 |
<0.001 |
|
Prednisone (or equivalent) ≥10 mg/d |
66.9 |
36.7 |
<0.001 |
|
ACR, American College of Rheumatology; DNA, deoxyribonucleic acid; SD, standard deviation; SLICC, Systemic Lupus International Collaborative Clinics P-values calculated using 2 sample t-test for comparison of means and chi-square test for comparison of percentages. |
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Acknowledgements:
Funded:
MedImmune. Editorial Assistance: K Alexander, QXV
Comms, an Ashfield business, UK
To cite this abstract in AMA style:
Furie R, Khamashta M, Wang L, Drappa J, Greth W, Illei G. Geographic Differences in Demographics, Clinical Characteristics, and Standard of Care in Multinational Studies of Patients with Moderate to Severe Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/geographic-differences-in-demographics-clinical-characteristics-and-standard-of-care-in-multinational-studies-of-patients-with-moderate-to-severe-systemic-lupus-erythematosus/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/geographic-differences-in-demographics-clinical-characteristics-and-standard-of-care-in-multinational-studies-of-patients-with-moderate-to-severe-systemic-lupus-erythematosus/