FEASIBILITY ASSESSMENT OF INDIRECT TREATMENT COMPARISON BETWEEN OFF-LABEL RITUXIMAB AND NOVEL TREATMENTS IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA
Author(s)
Mahmoud Hashim, PhD1, Alexa Sibiga, BSc2, Teige Bourke, PhD2, Sumeet Singh, MSc2, Alexander M. Litvintchouk, PharmD3, Ann Leon, PharmD3;
1Johnson & Johnson, Leiden, Netherlands, 2Eversana, Burlington, ON, Canada, 3Johnson & Johnson, Horsham, PA, USA
1Johnson & Johnson, Leiden, Netherlands, 2Eversana, Burlington, ON, Canada, 3Johnson & Johnson, Horsham, PA, USA
OBJECTIVES: Indirect treatment comparisons (ITCs) can inform comparative efficacy where head-to-head trials do not exist; however, differences in patient and study characteristics may introduce bias. Rituximab is used off-label as a 2nd-line treatment for warm autoimmune hemolytic anemia (wAIHA); new studies of targeted therapies call for contextualizing rituximab’s relative efficacy. This study assessed feasibility of ITCs between rituximab and emerging novel treatments.
METHODS: A systematic literature review (SLR) identified interventional studies in wAIHA published from 2013-2024. Feasibility of ITCs using standard (Bucher ITC or network meta-analysis) or population-adjusted methods (matching adjusted indirect comparison or simulated treatment comparison) was evaluated using published rituximab non-registrational trials, existing real-world evidence (RWE), and registrational trials for novel treatments.
RESULTS: From 3168 abstracts and 870 additional records identified (conference abstracts, regulatory records, bibliographies), 12 unique studies were included. Most exclusively enrolled participants with wAIHA or reported a wAIHA subgroup; 2 had mixed populations with >88% wAIHA participants. Most trials were ≥24 weeks long, with 3 lasting >2 years. Seven trials were single-arm; 5 were randomized (3 double-blind, 2 open-label). Four trials had control arms (3 placebo, 1 prednisolone).
Five trials studied rituximab in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Significant differences in study design, geography, eligibility criteria, endpoint definitions and timing, and sample sizes existed across studies, limiting comparison. Endpoint definitions in particular differed with regard to required hemoglobin changes/thresholds and exclusions (eg, no rescue therapy).
Standard comparison methods were infeasible due to lack of common comparators. Population-adjusted methods were limited due to heterogeneity in treatment line and background corticosteroid use, both critical prognostic variables.
CONCLUSIONS: An ITC using published rituximab trials was infeasible due to lack of a common comparator and heterogeneity in key prognostic variables. Rituximab trial results should not be directly compared with other treatments due to heterogeneity.
METHODS: A systematic literature review (SLR) identified interventional studies in wAIHA published from 2013-2024. Feasibility of ITCs using standard (Bucher ITC or network meta-analysis) or population-adjusted methods (matching adjusted indirect comparison or simulated treatment comparison) was evaluated using published rituximab non-registrational trials, existing real-world evidence (RWE), and registrational trials for novel treatments.
RESULTS: From 3168 abstracts and 870 additional records identified (conference abstracts, regulatory records, bibliographies), 12 unique studies were included. Most exclusively enrolled participants with wAIHA or reported a wAIHA subgroup; 2 had mixed populations with >88% wAIHA participants. Most trials were ≥24 weeks long, with 3 lasting >2 years. Seven trials were single-arm; 5 were randomized (3 double-blind, 2 open-label). Four trials had control arms (3 placebo, 1 prednisolone).
Five trials studied rituximab in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Significant differences in study design, geography, eligibility criteria, endpoint definitions and timing, and sample sizes existed across studies, limiting comparison. Endpoint definitions in particular differed with regard to required hemoglobin changes/thresholds and exclusions (eg, no rescue therapy).
Standard comparison methods were infeasible due to lack of common comparators. Population-adjusted methods were limited due to heterogeneity in treatment line and background corticosteroid use, both critical prognostic variables.
CONCLUSIONS: An ITC using published rituximab trials was infeasible due to lack of a common comparator and heterogeneity in key prognostic variables. Rituximab trial results should not be directly compared with other treatments due to heterogeneity.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA46
Topic
Study Approaches
Topic Subcategory
Meta-Analysis & Indirect Comparisons
Disease
SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)