In patients with AAV, 1st treatment rituximab has been shown not to trigger antibodies

A first course of rituximab is sufficient to trigger the development of anti-rituximab antibodies in patients with systemic lupus erythematosus (SLE), but not in those with ANCA-associated vasculitis (AAV), according to one study.

The researchers believed that rituximab might have similar effects in patients with SLE and AAV, two autoimmune diseases. However, the results of this study showed “the striking difference” in the occurrence of anti-drug antibodies, or ADA, triggered by rituximab treatment in the two groups of patients.

“After the first cycle of rituximab, no AAV patient was ADA positive compared to 37.8% of SLE patients,” the researchers wrote.

The study, “First exposure to rituximab is associated with elevated anti-drug antibody levels in systemic lupus erythematosus but not in ANCA-associated vasculitis, ”Was published in Arthritis Research and Therapy.

Rituximab is approved for use in AAVs both as induction therapy, to push disease into remission, and as maintenance therapy, when used to maintain patients in remission. It works by depleting B lymphocytes, a type of immune cell that produces antibodies and is overactive in AAV and other autoimmune diseases.

The therapy is available under the brand name Rituxan in the United States, under the name MabThera in Europe, or as biosimilars across the world.

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Although not approved for the treatment of lupus, rituximab is also used off-label in SLE, an autoimmune disease characterized by widespread inflammation and tissue damage.

Some people develop antibodies to rituximab as a result of an unwanted immune response, which may limit the effectiveness and safety of treatment. However, there are limited data on the development of anti-rituximab antibodies in particular groups of patients.

Now, a team of researchers in Sweden has examined how common it is for patients with AAV or SLE to develop such antibodies and how they can affect the effectiveness and safety of rituximab treatment.

The study included 22 AAV patients – 10 men and 12 women – with a median age of 62 years and a median disease duration of 1.5 years. Of the patients, 15 had granulomatosis with polyangiitis (GPA), six had microscopic polyangiitis (MPA) and one had eosinophilic granulomatosis with polyangiitis (EGPA).

The most common rituximab regimen given to these patients was 1 gram taken two weeks apart (in 59%, 13 patients). Just under half (10 patients; 45.4%) also received cyclophosphamide as part of their treatment.

A total of 66 patients with SLE (60 women) also participated in the study. These participants were younger, with a median age of 36.3 years, and their illness was longer, with a median duration of 7.9 years. The most common rituximab regimen was 375 milligrams per square meter of body surface area once a week for four weeks in 38 patients (57.6%). Methylprednisolone was prescribed in 37 (56.1%) of these patients, and 36 (54.5%) were also receiving cyclophosphamide.

After the first course of rituximab, none of the AAV patients developed anti-rituximab antibodies, the data showed.

This was in contrast to patients with SLE, of whom 25 (37.8%) developed antibodies at a median of six months after starting treatment with rituximab. Those who developed antibodies were on average 10 years younger (34 vs. 44.3 years) and had a more active disease with a shorter duration (4.14 vs. 9.19 years) than those who did not. not developed. Most cases (22) have occurred in patients receiving rituximab for lupus nephritis or inflammation of the kidneys.

Despite the overall reduction in SLE disease activity, measured using a tool called SLEDAI-2K, patients who developed antibodies to rituximab had a higher SLEDAI-2K score (6 vs. 4 ) and a higher proportion of B cells (4% vs. 0.5%) at six months follow-up than those who did not.

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Scientists say these results mean antibody development may affect how well rituximab works in these patients.

After the second cycle of rituximab treatment, three patients with antibody-positive SLE (25%) had immediate reactions to the rituximab infusion, and two (16.7%) had serum sickness or extreme sensitivity to the drug. rituximab, characterized by fever, rash and joint damage. inflammation or pain. Serum sickness was also reported in a patient without antibody (5.2%), while no immediate infusion reaction was reported in this group during treatment.

Next, to test for natural anti-rituximab antibodies, the researchers used blood samples from 41 AAV patients and 62 SLE patients who had never been treated with rituximab. One AAV patient and three patients with SLE had positive but very low levels of anti-rituximab antibodies.

“The presence of natural antibodies,” the researchers wrote, may reflect “the presence of a remarkably large repertoire of antibodies.”

Overall, the results suggest that the development of anti-rituximab antibodies is common in patients with SLE, drawing attention to the need for “screening for anti-rituximab antibodies prior to retreatment and investigation of immediate and late infusion reactions, ”the researchers wrote.

However, “such a phenomenon does not appear to be more relevant for AAV,” they added.

The team noted that “rituximab is commonly used for vasculitis associated with ANCA”.


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