Anti-Rituximab Antibodies Predictive of Infusion-Related Reactions in SLE

In patients with systemic lupus erythematosus (SLE), antidrug antibodies play a role in the lack of response or development of infusion-related reactions to rituximab, according to study data published in Annals of the Rheumatic Diseases.

The investigators sought to explore how the presence of antidrug antibodies is associated with infusion-related reactions and the effectiveness of rituximab treatment in patients with SLE. A total of 57 individuals who fulfilled American College of Rheumatology criteria were recruited from the lupus clinic at the University College London Hospital in the United Kingdom. All of the participants were receiving rituximab for the treatment of active SLE (according to British Isles Lupus Assessment Group [BILAG] A or 2B scores) for the first time. All confirmed infusion-related reactions were recorded in patients’ electronic health records.

Patient baseline characteristics, including complement C3, double-stranded DNA antibody titers (dsDNA), and BILAG scores, were recorded at the time of treatment and at each clinic visit. CD19-positive lymphocyte levels were measured at 1 and 6 months following rituximab therapy.

Study results showed that antidrug antibodies were identified in 37% of patients following treatment with rituximab. Patients who were positive for antidrug antibodies were significantly younger than patients who were not, both at diagnosis (P =.03) and at the time of initial treatment with rituximab (P <.001). In addition, antidrug antibodies were reported significantly more often in men than in women (P =.04). No significant differences were described with respect to the use of concomitant therapy, disease manifestations, or ethnicity. Moreover, at the time of rituximab treatment, no significant differences in C3, dsDNA titers, or BILAG scores were reported.

At 6 months after treatment, patients who were positive for antidrug antibodies demonstrated a significant increase in C3 levels (P =.003) and a significant reduction in dsDNA antibody binding (P =.008), in line with an effective response to treatment. Although significant normalization of C3 was observed at 6 months in patients who were positive for antidrug antibodies (P =.007), there was no significant improvement observed in dsDNA titers (P =.96).

All patients demonstrated a significant improvement in global BILAG score at 6 months following treatment (P <.0001). At 1 and 6 months post-treatment, however, no significant difference in CD19 was reported between patients with or without antidrug antibodies.

Of the 57 participants, 25 (18 positive and 7 negative for antidrug antibodies) underwent retreatment with rituximab. Although all of the patients who were positive for antidrug antibodies developed infusion-related reactions, there were no reactions reported in patients without antidrug antibodies (P <.001).

The investigators concluded that if the results of this study are validated, these findings may support routine screening for antidrug antibodies prior to treatment with rituximab, which may potentially identify patients at risk for developing infusion-related reactions and thus encourage greater caution and enhanced surveillance.

Reference

Wincup C, Menon M, Smith E, et al; ABIRISK Consortium. Presence of anti-rituximab antibodies predicts infusion-related reactions in patients with systemic lupus erythematosus [published online March 28, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215200