Introduction
IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory multi-systemic disease. Pancreato-biliary involvement is reported in up to 60%, which can lead to exocrine and endocrine pancreatic insufficiency. Glucocorticoids can be used to control active inflammation but are associated with substantial toxicity. B-cell depletion with anti-CD20 chimeric Rituximab (RTX) and anti-CD19 humanised Inebilizumab (INEB) are steroid-sparing and used to control disease flares. INEB is the only FDA-approved medication for the treatment of IgG4-RD.
Aims & Methods
Our aim was to compare B-cell depleting agents for the treatment of IgG4-RD. We searched PubMed, Cochrane Central Register of Clinical Trials and Embase databases for studies of maintenance therapy in IgG4-RD with a pre-defined strategy and performed a network meta-analysis to assess relapse at 12 months, occurrence of infections and infusion-related reactions.
Results
96 out of 2545 manuscripts underwent full text review after exclusions. Three studies met eligibility for the meta-analysis, two reporting the use of RTX and one of INEB (Table 1).
For the primary outcome of disease relapse at 12 months, INEB had a risk ratio (RR) of 5.8 (95% CI 0.29 - 115.02) and RTX had an RR of 2.29 (95% CI 0.19 - 28.21), with INEB being superior in preventing relapses. The RR for infections with INEB was 0.81 (95% CI 0.19 - 3.41) whilst with RTX was 0.62 (95% CI 0.13 - 3.04). The RR for infusion-related reactions with INEB was 1.27 (95% CI 0.09 - 18.76) and for RTX was 0.93 (95% CI 0.11 - 8.19). These must be interpreted in the context of study design; INEB in a phase 3 randomised trial following a stringent safety protocol for reporting of adverse events, and RTX in retrospective observational studies.
Author | Year published | Design | Country | Sample size | Comparison | Follow up (months) | Male |
Campochiaro | 2020 | Retrospective cohort | Italy | 14 | RTX vs placebo | - | 7 (50%) |
Majumder | 2018 | Retrospective cohort | US | 43 | RTX vs placebo | 34 / 27 | 34 (79%) |
Stone | 2024 | Randomised, placebo-controlled blinded | Global | 135 | Inebilizumab vs placebo | 12 | 88 (65%) |
Conclusion
This Network Meta-analysis demonstrates that INEB is superior to RTX at preventing disease relapses in patients with IgG4-RD at 12 months. Adverse events, such as infection and infusion-related reactions, were comparable in lieu of the methodological differences between studies.
Disclosure
Emma L Culver has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Dr Falk, Amgen, GSK, Mirum Pharma, Gilead, Chemomab, Zenus Bio, and Advisory/consultancy fees from Advanz/Intercept, IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Zenus Bio, Sanofi, Moderna and Sail BioPharma. MC has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Amgen, GSK, Mirum Pharma, Gilead, and Advisory/consultancy fees from Advanz/Intercept, Alphasigma, Albireo/IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Mayoly, Echosens, Kowa, Moderna, Zydus.