Session Information
Title: Systemic Lupus Erythematosus - Clinical Aspects: Non-biologic Disease-modifying Antirheumatic Drugs
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The Lupus Foundation of America Collective Data Analysis Initiative was established to evaluate SLE clinical trial design, using data collected from multiple studies. To evaluate the impact of baseline disease characteristics and background treatments on trial endpoints, we evaluated the effects of baseline disease severity and background medications on flare rates in non-nephritis patients.
Methods: Data from 186 SLE patients receiving standard-of-care (SOC) but no investigational agents were compiled from 3 multicenter non-nephritis Phase 2 or 3 trials. A flare (referred to as “any flare”) was defined as either >/= 1 new BILAG A or >/= 2 new B scores; a severe flare was defined as the occurrence of >/= 1 new BILAG A organ score since the previous visit. Treatments compared were: azathioprine, mycophenolate mofetil (MMF), methotrexate, and other including treatments such as antimalarials or low dose prednisone alone.
Results:
Those with severe disease at baseline (at least one BILAG A) were more likely to experience any flare as well as a severe flare. At baseline, mean BILAG composite scores for MMF patients was 26.2 (SD 8.2) vs 22.1 (8.5) for all other patients (p=0.01). MMF-treated patients with severe disease at baseline had the highest rate of any flare and severe flare. Flare rates in other SOC groups did not differ when compared to each other (data not shown).
Table 1. Any Flare** Stratified by Baseline Disease Severity and Background Drug
|
Background drug |
Baseline disease severity |
Total person-years |
Total number of any flares |
Rate of any flare |
P-value† |
|
MMF |
No BILAG A |
11.7 |
12 |
1.03 |
reference |
|
At least one A |
19.3 |
46 |
2.39 |
0.01 |
|
|
Other drugs |
No BILAG A |
48.3 |
44 |
0.91 |
reference |
|
At least one A |
51.3 |
72 |
1.40 |
0.02 |
** Defined as >/= 1 new BILAG A or>/= 2 new B scores any new A or 2+ new Bs since last visit.
† By fitting a Poisson regression model to the total number of flares and the total person-years for each background drug group.
Table 2. Severe Flare* Stratified by Baseline Disease Severity and Background Drug :
|
Background drug |
Baseline disease severity |
Total person-years |
Total number of severe flares |
Rate of severe flare |
P-value† |
|
MMF |
No BILAG A |
11.7 |
4 |
0.34 |
reference |
|
At least one A |
19.3 |
36 |
1.87 |
0.0013 |
|
|
Other drugs |
No BILAG A |
48.3 |
21 |
0.43 |
reference |
|
At least one A |
51.3 |
59 |
1.15 |
<0.0001 |
* Defined as >/= 1 new BILAG A since last visit.
Conclusion: Previously, we reported MMF to be associated with increased response rates based on a BILAG assessment, which may have been confounded by increased protocolized steroid use in studies contributing the majority of MMF-treated patients. We now report that in non-nephritis trials, patients entered on MMF had greater baseline disease, suggesting that treatment with MMF might define a sicker subset of patients. Our new data further indicate a higher propensity for all flares and severe flares in those on MMF at baseline despite increased response rates after high steroid use, consistent with the hypothesis that those more ill patients who do not respond to protocol therapy, are more likely to flare than other patients. Trial results could be confounded, then, by inconsistencies between endpoints defining response and endpoints relying more heavily on flare.
Disclosure:
K. C. Kalunian,
None;
M. Kim,
None;
T. W. Behrens,
Genentech and Biogen IDEC Inc.,
3;
S. Bongardt,
UCB,
3;
P. Brunetta,
Genentech Inc,
3;
P. Daly,
None;
N. Franchimont,
Biogen Idec Inc.,
3;
R. Furie,
Exagen,
5;
M. Linnik,
Lilly,
3;
B. H. Hahn,
Eli Lilly and Company,
5,
Biogen-IDEC,
5,
Astella Pharma ,
5,
Teva Pharmaceutical,
2;
L. M. Hanrahan,
None;
J. L. Hillson,
Bristol-Myers Squibb,
3;
J. Salmon,
None;
N. Solomons,
Vifor,
3;
J. T. Merrill,
None.
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