Pos0512 Sex-Related Differences in Trial Outcomes in Axial Spondyloarthritis Randomized Clinical Trials: A Systematic Literature Review and Meta-Analysis

Background: Sex-related differences in clinical manifestations and disease outcomes have been reported in axial spondyloarthritis (axSpA), however, limited information exists on sex-related differences in axSpA randomized controlled trials (RCTs). Objectives: Through a systematic literature review and meta-analysis we aimed to assess sex-related differences in participation, patient characteristics and efficacy and safety end-points of advanced therapies in axSpA patients participating in RCTs. Methods: We performed a systematic literature search in MEDLINE, EMBASE, Central and FDA databases, from January 2000 to March 19, 2023. We included RCTs that assessed the efficacy of advanced therapies in adult participants with axSpA. Two reviewers extracted information on the rates of the following end-points by sex: Assessment in Spondylarthritis International Society criteria (ASAS40/20), and the Ankylosing Spondylitis Disease Activity Score low disease activity/inactive disease (ASDAS-LDA/ID; ASDASResults: A total of 79 RCTs were included (23,748 participants). The ratio of male to female was around 2:1 (69.7% male participants). Only 9 trials (11.4%, 3,284 participants) reported sex-disaggregated baseline characteristics, 20 trials (25.3%, 6,159 participants) reported sex-disaggregated efficacy endpoints and 2 trials (2.5%, 816 participants) reported sex-disaggregated safety endpoints. Female patients were significantly older, had higher baseline BASDAI scores, and higher body mass index (BMI) (Table 1). Male patients had significantly higher baseline C-reactive protein (CRP) levels and were more likely to be HLA-B27 positive. There were significant differences in the pooled estimates of efficacy endpoints between male and female patients. Overall, male patients on advanced therapies were more likely to achieve an ASAS40 response compared to female patients (OR 1.79, 95% CI 1.30 to 2.47). This was significant for both IL-17 inhibitors (i) and TNFi (IL-17i: OR 1.65, 95% CI 1.15 to 2.37; TNFi OR 2.41 95% CI 1.19 to 4.88) (Figure 1a). All subgroup analyses showed a male preference for significantly improved ASAS 40 response across drug class, condition, and biologic exposure. There was substantial heterogeneity within almost all subgroups. Male patients were also more likely to achieve an ASDAS-ID or LDA response (OR 1.79, 95% CI 1.19 to 2.69). Similar effect size was found for achieving ASDAS-LDA/ID in male vs. female on IL-17i (OR 1.81 95% CI 1.06 to 3.07), and TNFi (OR 1.75, 95% 0.92 to 3.35) (Figure 1b). Two publications reported safety endpoints by sex. Overall, the proportion of serious adverse effects and discontinuation were similar, however sample sizes were quite small. Conclusion: Female patients participating in RCTs are less likely to achieve efficacy outcomes than their male counterparts. Similar sex-differences were found for IL-17i and TNFi. Further investigation is imperative, as it may help the development of sex-specific treatment approaches and novel drug targets. To better understand the differential drug efficacy between males and females, future clinical trials should diligently report sex-disaggregated data. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Lihi Eder AbbVie, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer Inc, Sandoz, UCB, Angel Gao: None declared, Jordi Pardo Pardo: None declared, Steven Dang: None declared, Lianne S Gensler Acelyrin, Fresenius Kabi, Eli Lilly, Janssen, Novartis, Pfizer, UCB in the last 24 months, Novartis and UCB in the last 24 months, Philip J. Mease Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Abbvie, Acelyrin, Aclaris, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Inmagene, Janssen, Novartis, Pfizer, Moonlake, Takeda, UCB, Ventyx, Abbvie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Genascence, Janssen, Novartis, Pfizer, UCB.