OP0251 SLE PATIENTS FROM NORTH AMERICA ARE OLDER WITH LESS SEROLOGIC ACTIVITY THAN OTHER POPULATIONS IN INTERNATIONAL CLINICAL TRIALS
Authors: Ewa Olech, Eduard van Rijen, Ali Ashrafzadeh, Alexander Kant, Joan T. Merrill
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Regional differences have been identified as potential confounders of SLE clinical trial results. Recently, no difference between treatment and placebo was observed in the US lupus patients when a significant treatment effect was observed in Europe<sup>1</sup>. <h3>Objectives</h3> To compare SLE serologic features/markers of active disease between different geographic regions in recent multinational clinical trials. <h3>Methods</h3> Laboratory data of 1005 subjects from four global randomized SLE clinical trials at baseline were examined. Mean/median C3 and C4 complement levels, prevalence of low C3 or C4 (<b>Low C3/C4</b>), positive anti-double stranded DNA (<b>DNA</b>), anti-Extractable Nuclear Antibodies (<b>ENA</b>), and high-titer Antinuclear Antibody (<b>ANA≥1:640</b>) in North America (<b>NA</b>) patients were compared to Asia (<b>AS</b>), Latin America (<b>LA</b>), Africa (<b>AF</b>), Western Europe (<b>WE</b>), and Eastern Europe (<b>EE</b>) <h3>Results</h3> NA patients were significantly older than patients in LA, AF, or AS but not WE or EE. Not surprisingly, they also had higher complement levels and the lowest rates of low C3/C4, DNA, ENA, and ANA ≥1:640. Our data confirm that age is an important factor in the prevalence of low complement and autoantibodies. However, there remained a marked difference in serologic activity between NA and EE, despite being close in age. Asian patients were the youngest, had the lowest complement levels and the highest rate of ENA &amp; DNA consistent with high disease activity. Low complement, but not DNA, was relatively common in Europe. LA patients, like Asians, had high rates of serologic activity but less incidence of low C3/C4, suggesting that this population may have intrinsic disease severity without being as acutely active. <h3>Conclusion</h3> SLE patients entering studies from North America are strikingly less likely to have markers of active disease than other regions, raising concerns for their suitability for trials. This appears to be associated, at least in part, with age, although more aggressive treatments cannot be ruled out. Asian subjects have the greatest prevalence of autoantibodies and low complement. Latin American patients have high prevalence of ANA≥1:640 and other autoantibodies, but less evidence of low complements. These findings may help to explain regional differences in treatment/placebo responses and emphasize the importance of geographical stratification and improved methods to screen out patients unsuitable for SLE trials. <h3>Reference</h3> [1] www.immupharma.co.uk <h3>Disclosure of Interests</h3> Ewa Olech Grant/research support from: Bristol Myers Squibb, Eduard van Rijen: None declared, Ali Ashrafzadeh Employee of: Employee of IQVIA, Alexander Kant: None declared, 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