TY - JOUR T1 - Time to change the primary outcome of lupus trials JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 581 LP - 582 DO - 10.1136/annrheumdis-2018-213788 VL - 78 IS - 5 AU - Frederic A Houssiau Y1 - 2019/05/01 UR - http://ard.bmj.com/content/78/5/581.abstract N2 - In ARD, a group of outstanding investigators report the results of another lupus trial missing its primary endpoint, namely the Phase III CHABLIS-SC study aimed at testing the efficacy of blisibimod,1 composed of a tetrameric BAFF/BLyS domain fused to a human IgG1 Fc region. Interestingly, blisibimod displayed unequivocal effects on biomarkers, such as reduction of circulating B cells, serum immunoglobulin titres or anti-DNA antibodies and increase in complement levels, changes in line with its mode of action and known to correlate with improved clinical outcome. Moreover, although the trial was not intended to demonstrate renal efficacy, an interesting reduction of proteinuria was noticed. This paradox raises the possibility that the failure of CHABLIS-SC stems more from the choice of the primary efficacy endpoint than from the drug itself, the more so as BAFF/BLyS was proven to be an appropriate target in four previous clinical trials, namely the belimumab BLISS-52,2 BLISS-763 and BLISS-SC4 and the tabalumab ILLUMINATE-25 studies, all showing the same effects on biomarkers and a significant, although modest, clinical efficacy. Of note, while the primary outcome (SRI-6) failed in the CHABLIS-SC trial, a trend (p=0.056) in favour of blisibimod was demonstrated when a modified endpoint was used, which takes into account, besides SRI-6, achievement of a steroid dose reduction between weeks 40 and 52 compared with day 1.The main goal of this editorial is to propose a ‘U loop’ in … ER -