Biomarker assays appear in most current autoimmune and rare autoimmune trial protocols. The eligibility thresholds for those assays are among the strongest protocol-level drivers of enrollment performance, and the calibration choices made during protocol design determine whether a study screens efficiently.
A 2025 analysis published in Inflammatory Bowel Diseases examined screen-failure (SF) patterns in 16,913 patients from 17 Phase II/III inflammatory bowel disease trials. SF rates averaged 44% in ulcerative colitis and 51% in Crohn’s disease. Candidates who did not meet the modified Mayo, endoscopic, or Simple Endoscopic Score for Crohn’s Disease thresholds required for entry were excluded. The pattern is consistent with what Worldwide sees in biomarker-rich studies across other immunology and inflammation indications.
A recent Phase IIb SLE study Worldwide delivered illustrates the operational picture. Across 20 countries and 102 sites, eligibility criteria included a SLEDAI score above six, a positive interferon gene signature, and ANA and anti-dsDNA thresholds. Of 707 patients screened, 185 were randomized. Global SF ran at 73.8%, with regional variation from 63.3% in APAC to 85.7% in the U.S. The last patient in was delivered one month ahead of schedule, and randomization exceeded the target of 178. The screening burden was substantial. Engineering it into the protocol design and the regional site footprint at the start was what allowed the timeline to hold.
What Protocol Design Decisions Look Like
A biomarker’s performance as an eligibility signal in real-world trial populations is determined at protocol design, before sites are selected.
Assay validation is foundational. Some autoimmune conditions still lack rigorously validated assays, and the test selected at protocol design defines what the screening data can support. When pathophysiology is incompletely understood, collaborating with academic centers or patient consortia during protocol development can surface biomarker options that neither the sponsor nor the CRO would identify on their own.
Eligibility threshold calibration is the next consideration. The same biomarker can be paired with different thresholds across concurrent trials, with each threshold defensible against its own reference data and inconsistent with the others. Calprotectin in IBD is one common example. Anti-saccharomyces cerevisiae antibody is another, although with positivity of 60-70% in patients screened for Crohn’s disease versus 10-15% in those screened for ulcerative colitis. Threshold calibration shapes whether a biomarker contributes meaningful eligibility precision or simply narrows the recruitment pool.
Participant burden in sample collection tends to get less attention in protocol design, but matters operationally. Minimally invasive collection improves recruitment yield in rare autoimmune conditions, specifically, where competition for participants is greater than in common autoimmune indications. A protocol that requires a tissue biopsy at screening recruits differently from one that requires a blood draw or a non-invasive imaging procedure, even when the underlying biomarker science is comparable.
What This Means for Enrollment Outcomes
Cross-indication patterns are consistent across IBD, SLE, lupus nephritis, and rare autoimmune populations. The biomarkers themselves vary. The protocol design choices that determine how biomarkers function as eligibility signals are what carry through across these indications.
For the full framework on biomarker eligibility design in immunology and inflammation trials, including biomarker tables by condition, the friction points framework, and recommended approaches at protocol design, our Autoimmune and Rare Autoimmune white paper provides the cross-indication view.
