OP0334 WHAT SEROLOGIC PROFILING PROVIDES OPTIMAL ENTRY CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS CLINICAL TRIALS?
Authors: Ewa Olech, Eduard van Rijen, Alexander Kant, Ali Ashrafzadeh, Joan T Merrill
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A major concern for SLE clinical trials is the possibility that some patients who technically meet entry criteria may not have active disease. Antinuclear antibody (<b>ANA</b>) is known to lack specificity for SLE, permitting inclusion of inappropriate patients. Typically, ANA≥1:80 and/or positive anti-double stranded DNA (<b>DNA</b>) are required screening elements, but lately other autoantibody variables have been utilized. <h3>Objectives</h3> To examine serologic features that promote entry of active SLE patients into trials while supporting reasonable recruitment rates. <h3>Methods</h3> Serologic features of 1411 individual subjects who had full laboratory data at screening (N=783) and/or baseline (N=1019) in 4 phase 2 multicenter SLE trials were examined. Complement levels, percent of patients with low C3 or C4, and elevated DNA were used as markers of active disease. Serological profiles consistent with active SLE were tested on screened population for effects on potential screen failure rates. <h3>Results</h3> Of 1019 patients who qualified for the studies (baseline population), 399 (39.2%) were positive for DNA and 670 (65.8%) had anti-Extractable Nuclear Antibodies (<b>ENA</b>). Patients with positive DNA or ENA (even in absence of DNA) had lower complement levels and were more likely to have low C3/C4. (Table 1) In patients at screening, higher titers of ANA were associated with lower complement levels and higher rates of patients with low C3/C4 and elevated DNA. ENA impacted complement levels even in the absence of ANA. Compared to traditional entry criteria (ANA≥1:80 and/or DNA), patients defined by positive DNA or ENA or ANA≥1:640 had significantly lower complement levels and greater rates of low C3/C4, suggesting a more active patient population. (Table 1) Compared to a 22.5% screen failure rate with the typical requirement for ANA≥1:80 or DNA, testing DNA or ENA or low C3/C4 as entry criteria resulted in 30.7% exclusion. Adding high titer (≥1:640) ANA as an additional optional criterion would decrease the screen failure to 25.7%. (Table 2) <h3>Conclusion</h3> The following entry criteria may help increase the likelihood that trial subjects have active SLE: <b>ANA≥1:640, or DNA, or ENA, or low C3 or C4</b>. To the extent that a modest loss of recruitment increases the probability of entering true, active SLE patients, these alternative constructs should be considered in future SLE trials. <h3> Disclosure of Interests:&nbsp;</h3> Ewa Olech Grant/research support from: Bristol Myers Squibb, Eduard van Rijen: None declared, Alexander Kant: None declared, Ali Ashrafzadeh Employee of: Employee of IQVIA, Joan T Merrill Grant/research support from: Genentech, UCB, GSK, EMD Serono, Pfizer, Celgene, Exagen, Bristol Myers Squibb, Medimmune/Astra Zeneca, Lilly, Amgen, Xencor, Neovacs, Consultant for: Genentech, UCB, GSK, EMD Serono, Pfizer, RemeGen, Celgene, Exagen, Bristol Myers Squibb, Medimmune/Astra Zeneca, Lilly, Immupharma, Amgen, Janssen, Sanofi, Neovacs, Anthera, Speakers bureau: UCB, GSK, EMD Serono, Bristol Myers Squibb, Medimmune/Astra Zeneca, Janssen