Session Information
Date: Monday, November 9, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment III: Biomarkers
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
Increased expression of genes inducible by type 1 interferons has been observed
in a subset of patients with systemic lupus erythematosus (SLE).
Oral corticosteroids (OCS) are used to manage the signs and symptoms of SLE,
with greater dosages needed for more severe disease. We explored associations between
elevated expression of type I interferon–inducible genes in blood (IFN-high) and
disease activity, complement C3 and C4 levels, autoantibodies to
double-stranded DNA (dsDNA) or ribonucleoproteins (Sm, RNP), and use of OCS.
Methods:
Baseline disease activity data (N=736) from two randomized controlled trials of
sifalimumab (NCT01283139) and anifrolumab (NCT01438489), which enrolled
patients with moderate to severe SLE (SLEDAI 2K≥6 and BILAG 1A or 2B and
PGA≥1.0 on prednisone and/or immunosuppressants) were pooled. A new
investigative-use only assay was used to determine IFN-high. Association
between disease activity scores (SLEDAI-2K and CLASI <10 or ≥10),
complement C3 or C4 (normal vs. low), autoantibodies to dsDNA, Sm, RNP
(negative vs. positive), OCS dosage (< 10 or ≥10 mg/day), and IFN-high
was assessed using chi-square tests.
Results:
Pooled data from 736 patients were available for analysis. Mean age was 39.6±11.9.
Ranges of SLEDAI and CLASI scores were 4–29 and 0–53, respectively, and 61% and
28% had SLEDAI 2K or CLASI scores ≥10. 57% received OCS ≥10 mg/day.
79% were IFN-high and had significantly greater odds of serological and
clinical disease activity and of receiving ≥ 10 mg/day of OCS compared with
patients who had low levels of type I IFN inducible gene expression in blood
(IFN-low, Table).
Conclusion:
Significant association of IFN-high with increased serological and clinical disease
activity suggests that type I interferons are key drivers of disease in this
cohort of patients with SLE. The association between IFN-high and greater OCS
use is consistent with these patients having more severe disease.
Association of Baseline
Type 1 Interferon (IFN)-Inducible Gene Expression Level in Whole Blood and
Serological and Clinical Disease Activity and OCS Use in Patients Enrolled in
Phase IIb Studies of Anifrolumab and Sifalimumab
|
Baseline measure |
IFN-low N (%) |
IFN-high N (%) |
Odds ratio (95% CI) p-value |
|
SLEDAI 2K |
|||
|
<10 |
76 (48) |
214 (37) |
1.6 (1.12, 2.28) p=0.009 |
|
≥10 |
81 (52) |
365 (63) |
|
|
CLASI |
|||
|
<10 |
136 (87) |
396 (68) |
2.99 (1.83, 4.89) p<0.001 |
|
≥10 |
21 (13) |
183 (32) |
|
|
Complement C3 |
|||
|
Normal |
128 (82) |
304 (53) |
3.99 (2.58, 6.17) p<0.001 |
|
Low |
29 (19) |
275 (48) |
|
|
Complement C4 |
|||
|
Normal |
146 (93) |
401 (69) |
5.89 (3.11, 11.15) p<0.001 |
|
Low |
11 (7) |
178 (31) |
|
|
Anti-dsDNA |
|||
|
Negative |
58 (42) |
76 (15) |
4.25 (2.8, 6.45) p<0.001 |
|
Positive |
79 (58) |
440 (85) |
|
|
Anti-Sm |
|||
|
Negative |
150 (96) |
403 (70) |
9.36 (4.3, 20.38) p<0.001 |
|
Positive |
7 (5) |
176 (30) |
|
|
Anti-RNP |
|||
|
Negative |
139 (92) |
375 (66) |
6.02 (3.26, 11.14) p<0.001 |
|
Positive |
12 (8) |
195 (34) |
|
|
Oral corticosteroid dosage |
|||
|
<10 mg/day |
81 (52) |
232 (40) |
1.59 (1.12, 2.27) p=0.01 |
|
≥10 mg/day |
76 (48) |
347 (60) |
|
To cite this abstract in AMA style:
Ranade K, Wang L, Brohawn P, Greth W, Drappa J, Illei G. High Interferon Gene Signature Is Associated with Increased Disease Activity, Reduced Complement C3 and C4, and Increased Oral Corticosteroid Use in Systemic Lupus Erythematosus (SLE) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/high-interferon-gene-signature-is-associated-with-increased-disease-activity-reduced-complement-c3-and-c4-and-increased-oral-corticosteroid-use-in-systemic-lupus-erythematosus-sle/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-interferon-gene-signature-is-associated-with-increased-disease-activity-reduced-complement-c3-and-c4-and-increased-oral-corticosteroid-use-in-systemic-lupus-erythematosus-sle/