Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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      withdrawn.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      steroid efficacy with background immune suppressants withdrawn.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).
    

Detailed description: 
      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.
    

Intervention name(s): Group B SLE one blood donation; Blood drawing only Group C; Group A SLE prospective study
Intervention type(s): Other; Other; Drug
Intervention description(s): Blood drawing, history, physical examination,medical record review, questionnaires, completion of disease activity measures including SLEDAI,BILAG, CLASI,PGA,PROs,LFA investigational systems, BICLA, SRI; Blood drawing and Brief medical history to ensure status of healthy control; Patients have history and physical exmamination at each visit. Blood is drawn at each visit. At baseline, any background immune suppressant is stopped and patients given depomedrol up to 160 mg IM which can be repeated up to four times in the first two weeks. Patients are seen again at week 2, 4 and monthly until the final flare visit at which time they donate blood, receive appropriate treatments and exit study. Patients may elect to continue in study for up to one year. The following disease activity measures are included: SLEDAI, BILAG, CLASI, PGA, PROs (including lupus PRO and SF-36 ant ptGA), joint counts, exploratory outcome measures,BICLA,SRI
Other intervention name(s): depomedrol; medrol; methylprednisolone
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: SLE; lupus; biomarkers; depomedrol; flare; disease activity