Background The SELENA flare index (SFI) has functioned well in clinical and clinical trial settings (1), but has the limitation that it classifies only severe versus combined mild/moderate flares.
Objectives Since mild flares are often clinically insignificant, and it is useful to distinguish flares by organ system, a revision of the SELENA flare index (2) was carried out to define severe, moderate and mild flares separately, in terms of clinical and/or treatment variables, and by organ system. This revised flare index (rSFI) is independent of SLEDAI and was compared to the original SFI in the ROSE trial of rontalizumab (anti-interferon alpha) in SLE (2).
Methods SLE patients with moderate to severe active SLE were enrolled in ROSE. Study investigators were trained on the use of the rSFI and other instruments before the start of the trial. rSFI was administered at scheduled study visits in the ROSE trial along the original SELENA flare index (SFI) and BILAG index. The new BILAG 2004 flare definition was used (severe = new or worse A, moderate = ≥2 B new or worse, mild = ≥1B or ≥3C new or worse). The proportion of patients with flares from week 4 to 24 was tabulated. Inter-instrument agreement between the different flare classifications was evaluated with Cohen’s kappa/weighted kappa coefficient.
Results The assignment of no flare/ mild-moderate flare/ severe flare was compared for the rSFI versus SFI. In general, there was substantial agreement between the rSFI and SFI (kappa 0.70, weighted kappa 0.73). The agreement between rSFI and SFI was better for the clinical part of the rSFI (kappa 0.69) than the treatment part of rSFI (kappa 0.35). The SFI showed fair agreement (kappa 0.30; weighted 0.39) and the rSFI showed moderate agreement (kappa 0.31; weighted 0.51) with the BILAG flare index. Many of the significant discrepancies between instruments (e.g., mild flare by rSFI, but severe by the BILAG flare index) were determined, after further review, to be correctable data reporting errors.
Conclusions The revised SFI (rSFI) had substantial agreement with the previously validated SFI, and the clinical portion of the rSFI, tested independently, showed the best agreement. The rSFI has better agreement with the BILAG flare index than the original SFI. Some discrepancies were due to data entry errors that can be avoided with improved site training. One possibility to improve flare endpoints would be to combine moderate and severe flares, as those are most likely to be clinically important.
References Petri M. et al Combined oral contraceptives in women with systemic lupus erythematosus. NEJM 2005 353(24): 2550-58.
Bayon J. et al. Revision of the SELENA flare index. Arthritis Rheum 2009. 60:S339
ACR 2012 Abstract # 2622
Disclosure of Interest: M. Petri: None Declared, J. Merrill: None Declared, R. Maciuca Employee of: Genentech employee, J. Davis Jr. Employee of: Genentech employee, W. Kennedy Employee of: Genentech employee