Effects of High Titers of Anti-Chimeric Antibodies Following Rituximab

Roberta Fenoglio¹, Laura Solfietti¹, Savino Sciascia² and Dario Roccatello¹, ¹Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bo, Turin, Italy, ²Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Torino, Italy

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoantibodies, autoimmune diseases, Biologic drugs, rituximab and treatment

Session Information

Date: Sunday, November 5, 2017

Title: B Cell Biology and Targets in Autoimmune Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Monoclonal antibodies (MoAbs) are highly successful in treating various immunological disorders. The development of anti-drug antibodies (ADA) against the therapeutic MoAb is relatively common. In recent years, knowledge of how to assess immunogenicity of biological drugs has improved. ADA are thought to form immune complexes with the MoAb, leading to accelerated MoAB clearance and low decrease levels in the blood stream. Several reports showed an inverse relationship between MoAb levels and anti MoAb antibody formation. Further, patients who develop ADA are more likely to present with infusion-related adverse effects. Acute infusion reactions, including anaphylaxis, develop in a close temporal relationship to MoAb infusion.

Among the others MoAbs, Rituximab (RTX), an anti-CD20 monoclonal antibody, often results in the production of human anti-chimeric antibodies (HACA).

In this study, we aimed to evaluate the presence of HACA in patients with poor response to treatment with RTX

Methods:

We assessed the incidence of anti-drug antibodies (ADA) in patients with autoimmune diseases treated with the RTX and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.

Results:

When investigating 37 patients treated with RTX, we found very high-titer of HACA (> 1,000 AU) in 5 patients (13.5%): 2 with Systemic Lupus Erythematosus (SLE), 2 with Membranous Nephropathy (MN) and 1 patient with Mixed Cryoglobulinemia (MC). Details are given in table 1. In 4 of them, high titers of HACA were clearly related to unresponsiveness to RTX treatment. In the other case the appearance of high HACA titers was consonant with a severe hypersensitivity reaction during RTX re-treatment.

Conclusion:

HACA detection and monitoring, especially in the cases of RTX re-treatment, could not only assure a safer administration, but also support a more rational strategy of treatment.

Case	Disease	# of cycles with RTX	steroid- therapy	HACA-Titer (AU)	RTX-level
1	SLE	1	Yes	15,720	ND
2	SLE	1	Yes	3,719	ND
3	MC	3	No	14,670	0
4	MN	1	No	1,007	0
5*	MN	2	No	10,363	0

Tab.I: Patient sample

Disclosure: R. Fenoglio, None; L. Solfietti, None; S. Sciascia, None; D. Roccatello, None.

To cite this abstract in AMA style:

Fenoglio R, Solfietti L, Sciascia S, Roccatello D. Effects of High Titers of Anti-Chimeric Antibodies Following Rituximab [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effects-of-high-titers-of-anti-chimeric-antibodies-following-rituximab/. Accessed .

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