Rituximab More Effective in Patients With wAIHA Than CAD, Review Finds

Treatment with rituximab is safe and effective in managing autoimmune hemolytic anemia (AIHA), and seems to be more beneficial for people with warm antibody autoimmune hemolytic anemia (wAIHA) than for those with cold agglutinin disease (CAD), a review study has found.

These findings indicate that wAIHA is more likely to result from an overactivation of antibody-producing immune B-cells, which are the therapeutic target of rituximab.

The study, “Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis,” was published in the journal Experimental Hematology & Oncology.

AIHA is an autoimmune disease characterized by the production of autoantibodies that attack and destroy red blood cells. It includes two variants, CAD and wAIHA, depending on whether autoantibodies bind more easily to red blood cells at lower temperatures (CAD) or higher (wAIHA).

Rituximab — marketed by Genentech and Biogen in the U.S. under the brand name Rituxan — is an antibody that targets B-cells, reducing their numbers. By lowering the levels of these overactive immune cells and the autoantibodies they produce, rituximab also minimizes the loss of red blood cells and resulting anemia.

Although some studies have suggested that treatment with rituximab could be beneficial for patients with AIHA and possibly for those with microangiopathic hemolytic anemia (MAHA), “the evidence of favorability for this treatment modality is not yet clear,” the researchers wrote.

Notably, MAHA is a form of anemia in which the destruction of red blood cells is not associated with immune system dysfunction.

This review study focused on summarizing the main findings of clinical trials and observational studies investigating the safety and efficacy of rituximab for the treatment of AIHA and MAHA.

Searches in four online databases — PubMed, Cochrane, Embase, and Google Scholar — led to a final selection of 37 studies involving 1,057 patients. Twenty-four of these studies were on AIHA and 13 on MAHA. Most of them were observational studies and 10 were comparative studies.

In most cases, patients received rituximab by intravenous infusions (directly into the bloodstream) four times weekly, at a dose of 375 mg/m², and were followed for a period ranging from six to 83 months (approximately seven years).

Pooled data revealed that the mean proportion of patients who responded to treatment (overall response rate) with rituximab was 84%. From these, 61% achieved a complete response, becoming symptom-free. Both treatment efficacy measures were highly variable between studies.

Sub-group analyses revealed that for those with AIHA, response rates tended to be better in patients with wAIHA (79%) than in those with CAD (66%). The same was seen for complete responses (49% in wAIHA vs. 14% in CAD).

“This implies that warm type AIHAs are more likely to be resulted from B-cell hyperactivity,” the scientists wrote.

As for those with MAHA, the response rate was 93%.

A total of 32 studies reported 138 adverse events involving 851 patients, corresponding to a 13% overall rate of adverse events. From these, 23.9% were infusion-related reactions (e.g. fever, skin rash), 24.6% were infections, and 29.0% were blood-related abnormalities such as low white blood cell counts. Most adverse events were mild in severity.

“The present investigation has provided overwhelming evidence for the first time that RTX [rituximab] is effective for AIHA and MAHA,” the researchers wrote.

“Finally, RTX is safe and well-tolerated for the treatment of [hemolytic anemia]. Few AEs [adverse events] have been reported with most of them being mild, and the AE rate was similar to those reported in other treatment modalities,” they added.