Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
Hypothesis: A reason for repeated disappointing outcomes of clinical trials testing targeted
 immune biologics for lupus may be the heterogeneity of the disease, exacerbated by the
 variable effects on immune homeostasis of the background medications that must be continued,
 in most study designs, in these flare-prone patients.

 Purpose of Study: This study was designed to purposefully study a population equivalent to
 the placebo group of typical trials in SLE. In Group A patients entered the trial in
 mild-moderate flare, were treated with depomedrol, and any background immune suppressants
 withdrawn. Biomarkers at entry on various medications can be compared to biomarkers after
 steroid efficacy with background immune suppressants withdrawn. Depomedrol usually wears off
 over one to three months. Patients were closely observed, with serial biomarkers drawn at
 monthly intervals or immediately at the time of a new flare. Those patients developing new
 flares donated blood samples, were immediately treated as deemed appropriate, exiting the
 study. Group A was designed for up to 50 patients and recruited a total of 41. An additional
 group of 62 SLE patients donated blood once without additional interventions in order to
 increase the power of exploratory cross-sectional biomarker analysis on different immune
 suppressants (Group B). A control population of matched, healthy individuals donated blood
 twice for the same biomarker studies to validate these assays (Group C).
Original Protocol for Group A: Patients with at least a SLEDAI score of 6 or a BILAG score of
 B in at least two organ systems or A in at least one organ system were immediately entered
 into this study once informed consent was obtained. Background immune suppressants (if any)
 were stopped and in about half of the patients hydroxychloroquine was also stopped. All
 patients immediately received a shot of depomedrol 160 mg IM. Over the next two weeks they
 could elect up to three more shots of depomedrol for a total of four shots by the two week
 visit period. A complete battery of blood tests to assess lupus disease was drawn at the
 screening visit, and monthly thereafter. Exploratory biomarker studies were drawn as often as
 weekly for some markers and as often as three times in the study (landmark visits) for
 others. Protocol Changes during course of study: Biomarkers were drawn at Day zero, week 2
 week 4 and monthly thereafter until flare. Patients who did not improve with protocol steroid
 treatments were withdrawn from Group A and immediately treated as warranted. Since there was
 no protocol-defined improving visit, they could not continue the protocol until flare.
 However their baseline samples were appropriate for study as part of Group B (see below).

 Landmark visits for Group A are defined as: 1.) screening (pre-dose, on background meds with
 active disease) 2.) two weeks or four weeks after screening as optimal to assess a patient
 who has stopped background meds and is now maximally improved (but at least one grade drop in
 BILAG scores in all organs entered at A or B or a four point drop in SLEDAI, otherwise the
 participant is deemed a treatment failure and could not participate further in Group A. 3.)
 Flare visit on no background immune suppression defined as an increase in SLEDAI of 4 points
 from maximal improvement or one new BILAG moderate (B) score AND the investigator considers
 the condition to be a significant flare with intent to treat. Patients were (whenever
 possible) seen within 3 days for the flare visit if flare occured between monthly scheduled
 visits.

 The primary purpose of this study was to evaluate the time to flare and safety of a treatment
 withdrawal protocol in patients with active, but non-organ threatening SLE. The following
 biomarkers were obtained for exploratory analysis: cytokine panel, B Cell studies, T Cell
 studies, autoantibody profiles, epigenetic and gene expression studies and flow cytometry
 studies.
Inclusion Criteria:

 SLE Groups (Group A and B):

 1. ACR criteria for SLE.

 2. At least two organ systems moderately active to a minimum of BILAG B or SLEDAI score
 of 6.

 Control group (Group C):

 1. Age, ethnicity and gender matched (2:1) with an SLE study participant.

 2. Free of active or major chronic disease as determined by brief history.

 Exclusion Criteria:

 1. Safety or circumstantial reasons why volunteer cannot comply with the protocol.