5F-01 - The association between immune-modulating advanced treatments and endometriosis outcomes in a large US database

Background: Although endometriosis is considered a hormonally-driven and treated chronic condition, it has a significant inflammatory and fibrotic mechanistic axis, and yet no inflammatory or fibrotic treatment currently exists.

Objectives: Indication expansion, or approval of alternative indication targets for existing approved treatments, is a valuable process to uncover underlying biology and promote rapid drug discovery. We evaluated whether existing immune-modulating advanced treatments (AT) were associated with endometriosis outcomes in a large US database.

Methods: Women with an endometriosis diagnosis (Optum Electronic Medical Records 2007-2023), prescribed an AT <=1 year of diagnosis (AT Group) or not (No AT Group), were followed and censored at time of event, lost to follow-up, or at time of new AT initiation. Outcomes included hysterectomy, laparoscopy, and endometrial ablation. Cox proportional hazards models adjusted for type of inflammatory disease, smoking, malignancy, comorbidities, body mass index, and oral contraceptive and hormone therapy use.

Results: There were 1631 females in the AT Group and 6675 in the No AT Group; 14% and 13% had a procedure during follow-up, respectively. The most common therapies were anti-TNF (N=805; 49%), PDE4 inhibition (N=274; 17%), and B cell depletion (N=238; 15%). In adjusted analyses, the AT Group demonstrated higher incidence of laparoscopy (HR=2.36; 95%CI=1.74-3.20), but not hysterectomy (HR=1.46; 95%CI=0.96, 2.22) or endometrial ablation (HR=1.87; 95%CI=0.98, 3.56) compared with the No AT Group.

Conclusions: Women with endometriosis receiving AT did not demonstrate lower incidence rates of outcomes compared with those not receiving AT (overall and by specific AT). Results may be due to confounding of underlying disease-related factors or that anti-inflammatory strategies to treat endometriosis may require combinatorial approaches. This methodology may be useful for exploring indication expansion in inflammatory and other chronic diseases.