Abstract Session
Immunobiology
John Stone, MD,MPH
Professor of Medicine; The Edward Fox Chair in Medicine
Massachusetts General Hospital , Harvard Medical School
Concord, Massachusetts, United States
No financial relationships with ineligible companies to disclose
135 subjects were randomized and received at least one dose of INEB (n=68) or PBO (n=67). Baseline demographics and disease characteristics were generally balanced between those receiving INEB and PBO (Table 1).
The primary endpoint was met, with INEB treatment significantly reducing the risk of IgG4-RD flares compared to PBO during RCP (hazard ratio 0.13; 95% CI: 0.06, 0.28; p< 0.0001) (Figure 1). The statistically significant treatment effect of INEB compared to PBO was seen for all key secondary endpoints (Table 2).
During the RCP, 66 (97.1%) INEB and 66 (98.5%) PBO participants had ≥1 treatment emergent adverse event (TEAE), the most frequent ( >10%) were COVID-19 (16 [23.5%] INEB, 13 [19.4%] PBO), lymphopenia (11 [16.2%] INEB, 6 [9.0%] PBO), and UTI (8 [11.8%] INEB, 4 [6.0%] PBO). No subjects died; no SAE occurred in >1 subject. AEs of special interest included infusion related reactions in 3 (4.4%) INEB and 5 (7.5%) PBO and serious and/or opportunistic infections in 6 (8.8%) INEB and 2 (3.0%) PBO. In INEB participants, serious infections included COVID-19, appendicitis, and diverticulitis, and opportunistic infections were herpes zoster.
Conclusion: The MITIGATE trial, the first randomized, double-blind, placebo-controlled study ever conducted in IgG4-RD, establishes the safety and efficacy of CD19-targeted B cell depletion with inebilizumab in IgG4-RD.
Table 1: Demographics and Baseline Characteristics
Figure 1: Kaplan Meier Plot for Primary Endpoint
Table 2: Key Secondary Endpoints for participants receiving INEB and PBO at Week 52
J. Stone: Amgen, 1, 2, 6, 7, Argenx, 2, Bristol-Myers Squibb(BMS), 5, Novartis, 2, 6, Sanofi, 2, Zenas, 2; E. Culver: Amgen Inc., 2, 12, MITIGATE Committee Member; A. Khosroshahi: Amgen Inc., 2, 12, MITIGATE Committee Member, Sanofi, 2, 12, Advisory board participant, Viela Bio, 2, 12, Advisory board participant; W. Zhang: Amgen Inc., 2, 12, MITIGATE Committee Member; E. Della Torre: Amgen Inc., 2, 12, MITIGATE Committee Member; K. Okazaki: Amgen Inc., 12, MITIGATE Committee Member; Y. Tanaka: AbbVie, 6, Asahi-kasei, 6, Astellas, 6, AstraZeneca, 6, Boehringer Ingelheim, 5, 6, Chugai, 5, 6, Daiichi Sankyo, 6, Eisai, 6, Gilead, 6, GSK, 6, Lilly, 6, Pfizer, 6, Taisho, 5, 6, UCB, 6; M. Löhr: Amgen Inc., 12, MITIGATE Committee Member; N. Schleinitz: Amgen Inc., 2, 12, MITIGATE Committee Member; L. Dong: Amgen Inc., 12, MITIGATE Committee Member; H. Umehara: Amgen Inc., 12, MITIGATE Committee Member; M. Lanzillotta: Amgen Inc., 12, MITIGATE Committee Member; Z. Wallace: Amgen Inc., 2, 12, MITIGATE Committee Member; M. Ebbo: Amgen Inc., 12, MITIGATE Committee Member; G. Webster: Amgen Inc., 12, MITIGATE Committee Member; F. Martinez Valle: Amgen Inc., 12, MITIGATE Committee Member; M. Nayar: Amgen Inc., 12, MITIGATE Committee Member; V. Rebours: Amgen Inc., 12, MITIGATE Committee Member; C. Perugino: Amgen Inc., 2, 12, MITIGATE Committee Member; X. Dong: Amgen Inc., 3, 11; Y. Wu: Amgen Inc., 3, 11; N. Rampal: Amgen Inc., 3, 11; D. Cimbora: Amgen Inc., 3, 11.