Real-world analysis examines rituximab use in CAD
Treatment led to improvements, but often were short-lived, a US study finds
Treatment with rituximab led to improvements in biomarkers of red blood cell destruction among people with cold agglutinin disease (CAD), but the improvements often were short-lived and reversible, according to a real-world analysis in the U.S.
The therapy, which often is used off-label for the rare autoimmune disease, also was associated with about a threefold elevation in the occurrence of serious infections.
These were the findings of a Sanofi-sponsored analysis presented Dec. 11 at the 65th annual meeting of the American Society of Hematology (ASH) in the poster “A US Retrospective Observational Study of Rituximab Use in Cold Agglutinin Disease.”
Sanofi markets Enjaymo (sutimlimab-jome), the only approved therapy for CAD in the U.S., and also shared during the meeting promising early trial data from a potential Enjaymo successor called SAR445088.
In CAD, the body attacks and destroys its own red blood cells — a process called hemolysis — at cold temperatures. The self-reactive antibodies that drive these autoimmune attacks, called cold agglutinins, are produced by immune B-cells.
Rituximab, infused directly into the bloodstream, is an antibody-based therapy designed to target and deplete B-cells by binding to the CD20 protein on their surface. In the U.S., it’s approved to treat certain blood cancers and autoimmune diseases, where it is sold under the brand name Rituxan, with biosimilars available.
While CAD patients are commonly treated with off-label rituximab, there is a lack of real-world data related to patterns of its use or its safety and effectiveness in this patient population.
Aiming to fill that knowledge gap, the researchers retrospectively analyzed data from Optum’s de-identified Market Clarity Dataset focusing on adult CAD patients who had started on rituximab in the U.S. between 2007 and 2021.
Design of the CAD rituximab analysis
Of the 611 CAD patients identified, 124 were started on rituximab after their diagnosis, and 94 of them appeared to have primary CAD, a form of the disease that is not secondary to other underlying conditions (e.g., cancer or infections).
The analysis focused on these 94 people, who had a median age of 72 and tended to have more severe disease at treatment start than the larger group of all CAD patients.
Rituximab was begun at a median of 43.5 days (about 1.5 months) after patients’ CAD diagnosis and was used as a single therapy in the majority of cases. The mean number of rituximab treatment courses per person was 1.45.
All patients initiated a first course of treatment, with 78.8% finishing that cycle. Only about a quarter (25.5%) started a second cycle, which was completed by 62.5% of them.
About 40% of patients required a rescue blood transfusion at a median of about one month after initiating rituximab. Moreover, 57.4% also were given corticosteroids — a type of immunosuppressive medication — during their first course of rituximab, but a similar proportion of patients had used this type of medication in the year before.
Rates of infections and blood-clotting events
Because rituximab promotes the death of a subset of immune cells needed to fight off infections, it may increase the risk of infections. In these patients, the rate of serious infections was about three times higher in the three to six months after starting rituximab than it had been prior to treatment.
The rate of blood clot-related events also was slightly higher, and occurred faster, among rituximab-treated patients compared with all CAD patients.
About two-third of patients (66%) had available data on blood biomarkers of hemolysis at treatment start and during follow-up. These included low levels of hemoglobin, the protein in red blood cells that carries oxygen, as well as elevations in bilirubin — a substance made in the liver when red blood cells are broken down — and lactate dehydrogenase (LDH), an indicator of organ damage.
Data showed that about 70% of patients experienced a clinically meaningful increase in hemoglobin of at least 2 g/dL after a median of 48 days (about 1.5 months), which was maintained for a median of 44 days. But for more than two-thirds of these patients (68.3%), hemoglobin levels declined again at some point.
Moreover, about 60% of patients saw at least a 50% drop in bilirubin levels and about 30% experienced such a decline in LDH levels, both of which were sustained for about two months. Among these patients, more than half (53.6%) saw their bilirubin levels eventually rise again, and 80% experienced a reversion in LDH levels.
“Although patients treated with rituximab had some favorable changes in their biomarker levels … the change was sustained for a short duration, and most of the patients had reversal in biomarker levels to pre-rituximab levels,” the researchers wrote in the poster.
Possible influences and study limitations
They noted, however, that these biomarkers could have been influenced by blood transfusions or other medications being used during the study, and that the small number of patients also was a limitation.
“However, given that CAD is a rare disease and that the sample size identified in this study is larger than in most other studies, it is an important contribution to the growing literature on CAD and rituximab treatment for the disease,” the researchers concluded.