#AANAM – Rituximab Effective in Real World in Adults With Refractory gMG

Editor’s note: The Myasthenia Gravis News team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, April 17–22. Go here to read the latest stories from the conference

Rituximab, an approved immunosuppressive treatment for certain cancers and autoimmune conditions, effectively eases disease severity and prevents relapses in adults with generalized myasthenia gravis (gMG) who fail to respond to available therapies, according to a small, real-world study in Argentina.

Notably, neither high doses of rituximab nor regular maintenance doses were necessary for most patients to achieve disease remission and reduce immunosuppressive treatment, the researchers noted. This result was found both with patients with antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK).

These findings add to those of other real-world studies supporting rituximab as an effective treatment for MG, including in patients who fail to respond to standard treatment.

Juan Castiglione, MD, of the FLENI Institute, in Argentina, presented the study’s findings at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting, held online April 17–22. His oral presentation was titled “Long-term remission with rituximab in refractory generalized myasthenia gravis.”

In MG, the immune system produces antibodies that mistakenly attack proteins involved in the communication between nerve cells and muscle cells, leading to muscle weakness and fatigue.

AChR, which facilitates this communication, is the most frequent target in MG, while about 10% of myasthenia gravis patients have antibodies against another protein called MuSK.

Several treatments are available for MG, but about 15% of patients fail to respond or experience disease progression while on treatment. In such cases, the disease is called refractory.

Rituximab is an approved treatment for certain blood cancers and rheumatoid arthritis, an autoimmune disease that mainly affects the joints. It is marketed as Rituxan, by Biogen, in North America and Japan, and as MabThera, by Roche’s subsidiary Genentech, in Europe. Other brand names are used elsewhere and biosimilars of the therapy also are available.

The therapy’s recommended regimen is a first dose of 1,000 mg on day 1, followed by 1,000 mg on day 15, for a total of 2,000 mg. Maintenance doses can be administered, if necessary, every six months.

Because it depletes B-cells — immune cells that produce antibodies and are involved in autoimmune diseases — by targeting the CD20 receptor at their surface, rituximab also is used off-label to treat other autoimmune disorders, such as MG.

While clinical trials of rituximab in MG are underway, current guidelines recommend the off-label use of rituximab in patients positive for anti-MuSK antibodies and those who fail to respond to initial immunotherapy.

Now, researchers at the FLENI Institute evaluated rituximab’s long-term effectiveness in 16 adults — 13 women and three men, with a mean age of 45 — with refractory gMG, who were followed at their institute for at least two years. All patients had been referred to FLENI between January 2015 and October 2020.

Half of the patients were positive for antibodies against AChR, while the other half had anti-MuSK antibodies.

The age of disease onset was similar between the two groups. However, the MuSK group had a female predominance (100% vs. 63%), meaning all patients were women, significantly shorter disease duration (11 vs. 83.5 months), faster progression to generalized disease (24 days vs. 107.5 days), and more severe disease than the AChR group.

All patients had received immunosuppressive treatment — intravenous immunoglobin (94%) and/or plasma exchange (31%) — prior to rituximab. Among them, 10 received this type of rescue therapy for MG crises in the intensive care unit.

Nine patients were treated with a low-dose rituximab regimen. Seven of them received two 500 mg doses within two weeks, and two patients were given three 500 mg doses within three weeks. Seven patients were given the recommended regimen of two 1,000 mg doses within two weeks.

Despite the absence of clinical relapses, five patients (31%) — three with anti-AChR antibodies and two with anti-MuSK antibodies — received maintenance therapy with rituximab.

The team assessed changes using several measures. One was the patients’ MGFA Post-intervention Status (MGFA-PIS), which measures changes in MG clinical signs after rituximab treatment. The researchers also used the MG Status and Treatment Intensity (MGSTI) score, a measure composed of the MGFA-PIS and the dose of immunosuppressive treatments, and the number of CD20-positive B-cells.

MGSTI scores range from 0 to 3, with higher scores indicating worse disease. A score of 2 or better was used to define a favorable outcome.

The results showed that all patients had a “remarkable” drop in CD20-positive B-cell numbers, which remained undetectable at six and 12 months (one year) after treatment, and attained clinical remission, without new relapses, Castiglione noted.

This was associated with a reduction both in disease symptoms and in the use and dose of immunosuppressive treatments, with MGSTI scores of 2 or better being achieved by all patients. However, “this goal was reached significantly faster in the MuSK group,” Castiglione said.

Notably, “both groups achieved clinical remission with minimal doses of immunosuppressants” at two years after rituximab treatment, he added.

These findings highlighted that “rituximab is an effective therapeutic option, both in MuSK and in refractory AChR patients,” that allows the achievement of undetectable CD20-positive B-cells or clinical remission with minimal dose of immunosuppressants, without the need for high induction doses or regular maintenance therapy, Castiglione said.

“In low- and middle-income countries, such as Argentina, the impact of low-dose rituximab therapy represents a paradigm shift in decision making for long-term treatments,” Castiglione concluded.