Presence of anti-rituximab antibodies predicts infusion-related reactions in patients with systemic lupus erythematosus

Background: Rituximab is commonly used for systemic lupus erythematosus (SLE) but secondary non-depletion and non-response (2NDNR) associated with anti-drug antibodies is a notable problem with repeat rituximab cycles. Other B cell-targeted therapies include other anti-CD20 monoclonal antibodies or belimumab. Objective: To compare efficacy of switching to alternative anti-CD20 agents vs. belimumab in SLE patients with 2NDNR to rituximab. Methods: One hundred and twenty five patients received rituximab and had evaluable data. 77/125 received repeat rituximab cycles. Of these, 14/77 (18%) had 2NDNR. 8/14 patients were switched to belimumab (CD20-to-belimumab group) and 6/14 patients were switched to an alternative humanised anti-CD20 agent (CD20-to-CD20 group, ocrelizumab n = 3, ofatumumab n = 2, obinutuzumab n = 1). Efficacy was assessed using the BILAG-2004, SLEDAI-2K, SRI-4, and daily prednisolone requirement at baseline and 6 months. Results: In the CD20-to-belimumab group, only one patient achieved an SRI-4 and 2/8 patients had new/worsening BILAG-2004 grade A for lupus nephritis. There was no improvement in SLEDAI-2K; median (IQR) was 11.0 (9.5-14.8) at baseline and 10 (9.5-15.5) at 6 months. Median (IQR) prednisolone dose increased from 7.5 mg (4.4-12.5) to 10 mg (6.3-10). In the CD20-to-CD20 group, all 6 patients achieved an SRI-4. Median (IQR) SLEDAI-2K improved from 16.0 (10.3-24.0) at baseline to 5.0 (2.5-6.0) at 6 months. Median (IQR) prednisolone dose decreased from 15 mg (15-15) to 10.5 mg (5.3-15.0). Conclusion: This is the first assessment of belimumab's efficacy in a post-rituximab population. Our data suggests that patients with 2NDNR to rituximab, which constituted 11% of all patients initiated on this drug, should be switched within the same biologic class to another anti-CD20 agent.

show abstract

“…We called this secondary non-depletion and non-response (2NDNR) ( 8 ). This phenomenon has also been reported by other groups ( 20 ).…”

Section: Methodssupporting

confidence: 91%

Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This profound depletion usually lasts up to 8–12 months in the majority of RA patients, and can persist even longer in other patients, such as those with systemic sclerosis and vasculitis (data not shown). At 3 months, however, a checking is recommended to identify the small fraction of patients that may show an incomplete depletion and/or an early B cell repopulation, due to an accelerated MoAb clearance or to resistance phenomena (i.e., the development of anti‐MoAb antibodies) (Dunn et al, 2018; Leandro et al, 2016; Wincup et al, 2019). If at three months total B cells remain virtually absent no further B cell subsetting is technically possible (nor meaningful), and patients can be retested at 2 months intervals thereafter.…”

Section: Resultsmentioning

confidence: 99%

The ISCCA flow protocol for the monitoring of anti‐CD20 therapies in autoimmune disorders

Gatti¹,

Buccisano

Scupoli

et al. 2020

Cytometry Part B Clinical

View full text Add to dashboard Cite

Background: Anti-CD20 monoclonals (MoAbs) are used in a variety of autoimmune disorders. The aim is to eliminate memory B cells sustaining the tissue damage and the production of pathogenic autoantibodies, while preserving naïve cells. The disappearance of memory B cells and the repopulation by naïve cells correlate with good clinical response, while the reappearance of memory B cells and plasmablasts correlates with relapse or resistance to therapy. Anti-CD20 induce extremely low B cell levels, requiring high-resolution techniques. The immune monitoring protocol developed by ISCCA is described and validated, to provide a standardized method for the clinical decision-making process during anti-CD20 therapies in autoimmune diseases.

show abstract

“…As far as the treatment continuation is concerned, it is generally advised to avoid further infusions of rituximab as reappearance or worsening of symptomatology have been reported (6,10,11) and continuation of treatment with other anti-CD20 antibodies such as ofatumumab (fully-human) or obinutuzumab (humanized) has shown to be effective and safe (12,13). Drug desensitization generally has no use in delayed hypersensitivity reactions as RISS, although a successful case has been anecdotally reported (5).…”

Section: Discussionmentioning

confidence: 99%

Rituximab-induced Serum Sickness in Lymphoma: A Case Report

Navarro‐Matilla

Ramírez-García

Sancho-López

et al. 2021

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Presence of anti-rituximab antibodies predicts infusion-related reactions in patients with systemic lupus erythematosus

Cited by 35 publications

References 6 publications

Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab

Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab

The ISCCA flow protocol for the monitoring of anti‐CD20 therapies in autoimmune disorders

Rituximab-induced Serum Sickness in Lymphoma: A Case Report

Contact Info

Product

Resources

About