Background/Purpose: Multiple outcome measures have been utilized in SLE clinical trials. Consistency of response assessed by different instruments enhances confidence in the efficacy of pharmacologic interventions.  We recently reported results from both phases of a two-part pilot study [8 week double-blind (DB) placebo (PBO)-controlled phase followed by a 44 week open-label extension (OLE)] of repository corticotropin injection (RCI) in subjects with persistent SLE disease activity requiring corticosteroids.  Although the primary endpoint of the DB phase (a novel responder index described below, assessed at Week 4) was not met, RCI therapy led to improvement in several measures of disease activity by week 8. This post hoc analysis evaluated the efficacy of RCI over the entire 52 week study, as assessed by multiple standard disease activity indices (DAIs) and by a novel composite measure of organ-specific disease activity. 

Methods: Thirty eight subjects with active SLE including rash and/or arthritis despite moderate dose corticosteroids were randomized to RCI (n=26) or PBO (n=12) for the DB period; 33 completed through Wk 8 and entered the OLE (RCI/RCI n=22, PBO/RCI n=11), and 20 completed through Week 52 (RCI/RCI, n=13; PBO/RCI, n=7).  There were 36 subjects in the mITT population (RCI/RCI, n=25; PBO/RCI, n=11).  Efficacy of RCI was assessed every 4 weeks by total BILAG, SLE responder index (SRI), Cutaneous Lupus Disease Area & Severity Index (CLASI) Activity, Tender & Swollen Joint Count, Physicians Global Assessment (PGA), severe flare by SFI, and by hybrid SLEDAI (hSLEDAI) score every 2 weeks for the first 8 weeks, then every 4 weeks for the remainder of the combined 52 week study.  A novel organ-specific composite responder index, defined as decrease in hSLEDAI score from 4 to 0 for arthritis OR decrease in hSLEDAI score from 2 to 0 for rash AND no BILAG worsening in any other organ systems as compared to study baseline, was also evaluated at 4 week intervals.  RCI dose was defined by the protocol during the DB phase (Weeks 1-8), but could be adjusted within specified parameters by the investigator to achieve stable improvement in disease activity during the OLE (Weeks 9-28). Corticosteroid dose was required to remain stable through Week 20, after which taper was encouraged. 

Results: See Table

Conclusion:  Disease activity, reflected by several standard outcome measures, was generally concordant at both Weeks 8 and 52, with improvement in most DAIs seen at Week 8 for subjects randomized to RCI, but not PBO, during the DB phase, and for all subjects in the OLE at Week 52.  Directional trends in the novel organ-specific responder index employed were similar to those for standard DAIs at week 8 but did not seem to mirror other DAIs at Week 52.  Inconsistency between the novel organ-specific responder index and standard DAIs at Week 52 likely relate to a higher BILAG threshold to be considered a responder for the novel index.