Background/Purpose:

Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody that is commonly used in the treatment of severe and refractory SLE. Although generally well tolerated, infusion-related reactions do occur and can be severe / life threatening. At present it is not possible to predict which patients are at risk of developing these reactions. A major limitation to biologic therapy is the formation of anti-drug antibodies (ADA). To date, ADA to rituximab have not previously been studied in detail.

In this study, we assessed the prevalence of ADA to rituximab in patients receiving treatment for SLE and how this related to therapeutic efficacy and prediction of infusion reactions.

Methods:

We assessed for the presence of rituximab ADA using a Meso Scale Discovery Platform in 57 patients with SLE attending University College London Hospital (UCLH), UK. A subgroup of 42 patients were followed up longitudinally for up to 8 years following the first dose of rituximab. Clinical parameters including BILAG, complement C3 levels, dsDNA titres, lymphocyte count and CD19 positive B-cells were recorded. A retrospective review of patient records was undertaken to assess for the occurrence of infusion-related reactions. Mann Witney U test was used to compare differences between ADA positive (+ve) and ADA negative (-ve) groups. Paired t-tests were used to assess for changes in variables both immediately before and six months after treatment. P-value of <0.05 was considered statistically significant.

Results:

Of the 57 patients recruited, 88% were female (50/57) with a mean age of 38.9 years old. Mean disease duration was 102 months. ADA to rituximab were detected in 37% of patients (21/57). Those who developed ADA were significantly younger than ADA -ve patients (mean age 31.9; p<0.001) although no difference in disease duration between the two groups was observed (p=0.37). Males were also more likely to develop ADA than females (p=0.04). Patients receiving rituximab for the treatment of nephritis were more prone to develop ADA (p=0.03).

Following retreatment with rituximab, all ADA +ve patients developed infusion-related reactions. No reactions were seen in those who were ADA -ve. There was no difference in the efficacy of B cell-depletion between ADA +ve and ADA -ve patients (as measured by CD19 +ve B-cell count at six months; p=0.93). C3 levels showed statistically significant improvements in both groups six months post-treatment. A significant improvement in dsDNA titres was seen in those who were ADA -ve (p=0.008). However, there was no statistically significant improved in dsDNA titres in those who were ADA +ve at six months (p=0.96).

Conclusion:

We have detailed ADA to rituximab in a cohort of SLE patients who have undergone B-cell depletion therapy for the first time. Younger patients, males and those receiving treatment for nephritis were at increased risk of developing ADA. In patients who were ADA +ve there was no significant improvement in dsDNA levels at six months post-treatment. We found that the presence of these antibodies prior to retreatment predicted infusion-related reactions in all cases.

In future, routine screening for rituximab ADA will help predict those at risk of subsequent infusion-related reactions.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-presence-of-anti-rituximab-antibodies-predicts-infusion-related-reactions-in-patients-with-systemic-lupus-erythematosus/