Background/Purpose: Discrimination between treatment and placebo is problematic in lupus trials. Recently, composite endpoints have evolved which define response by both improvement in baseline findings and lack of clinically significant deterioration in other features. The predominant endpoints, the SLE Responder Index (SRI) and BILAG-Based Composite Lupus Assessment (BICLA), do not preclude the designation of response if there is one new moderate organ score (BILAG B) vs baseline but do exclude >/=2 new BILAG B scores. The British Isles Lupus Assessment Group (BILAG) has reported a provisional definition of flares (1). Here a moderate flare is defined as >/=2 B scores rated either new or worse. We addressed this disparity in defining a moderate, clinically significant deterioration in a cohort study.

Methods: The BILAG 2004 index was prospectively scored at the time of 182 clinic encounters of 91 patients.  Overall disease worsening was retrospectively judged by a clinician as either no worsening, mild, moderate, or severe flare.

Results:  

Flares receiving one new BILAG B score or one new or worse B were usually considered mild by the clinician, confirming the approach by both constructs to discount increased disease at B level in only one organ as a moderate flare. Using the clinician’s judgement as a standard to distinguish moderate flares, the sensitivity of the BILAG cutoff of >/= 2 B “new or worse” (detecting all flares that were as severe or more severe than the cutoff) was 60.0% as opposed to 26.7% for the SRI/BICLA definition of >/= 2 “new” B scores. Specificities were 97.1% and 99.3% respectively.

Conclusion:   Whether worsening is defined by “new” or “new or worse” moderate disease, one BILAG B in isolation does not usually represent clinically significant deterioration by clinical judgement.  Limiting the definition of moderate deterioration to 2 “new” B scores, which is now common practice in clinical trials for lupus, is a very insensitive measure for the degree of clinical deterioration considered moderate (or worse) by a physician. The concept of moderate flare defined by the BILAG group (>/= 2 “new or worse” B scores) might be a more helpful approach to define a threshold of moderate, clinically significant deterioration in composite endpoints for SLE trials.

1. Isenberg DA, Allen E, Farewell V, et al. An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA. Annals of the Rheumatic Diseases. 2011;70:54-59.