Early rituximab treatment may improve long-term outcomes in gMG
Follow-up study: Patients receiving therapy later were hospitalized more
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- Early rituximab treatment for generalized myasthenia gravis improves long-term outcomes.
- Patients treated early had fewer hospitalizations and less need for rescue therapies.
- Rituximab targets B-cells, reducing self-reactive antibodies in gMG.
Starting rituximab earlier after the onset of generalized myasthenia gravis (gMG) may be associated with better long-term outcomes, including fewer hospital admissions due to disease worsening and the need for rescue treatments.
That’s according to up to five-year results from a follow-up study of participants in the Phase 3 RINOMAX clinical trial (NCT02950155), which assessed the treatment’s safety and efficacy against a placebo in newly diagnosed gMG patients.
According to researchers, “it can be speculated that B cell-depleting therapies [such as rituximab] in [gMG] are more efficacious early after disease onset compared with in states of refractory [treatment-resistant] disease.”
The study, “Rituximab in New-Onset Generalized Myasthenia Gravis: Long-Term Follow-Up of the RINOMAX Clinical Trial,” was published in the European Journal of Neurology by a team of researchers in Sweden, where the trial was conducted.
Rituximab targets cells that produce self-reactive antibodies
Myasthenia gravis (MG) is caused by self-reactive antibodies that attack proteins involved in nerve-muscle communication. For most patients, these antibodies target acetylcholine receptor (AChR) proteins on muscle cells. The most severe form of the disease is gMG, in which the typical symptoms of muscle weakness and fatigue may affect many muscles throughout the body.
MG treatments usually include corticosteroids and immunosuppressants that help reduce the overactivation of the immune system and the production of self-reactive antibodies.
Rituximab is an antibody-based therapy designed to eliminate B-cells, the immune cells that produce self-reactive antibodies. Although not specifically approved for MG, it is sometimes used off-label in certain patients with refractory disease.
However, the RINOMAX trial showed that rituximab may be beneficial when given to newly diagnosed gMG patients. The study enrolled 47 people across seven sites in Sweden, who were randomly assigned to receive either a single rituximab dose (25 participants) or a placebo (22 participants) as an add-on to standard care.
Most participants were men, and the majority had late-onset MG and anti-AChR antibodies.
Top-line results demonstrated that a significantly higher proportion of patients in the rituximab group met the study’s main goal of achieving minimal disease manifestations after four months, compared with those on the placebo (71% vs. 29%).
Minimal disease manifestations were defined as a Quantitative MG Score (QMG) of four points or lower, low doses (10 mg or lower) of the corticosteroid prednisolone, and no need for rescue treatment (high doses of prednisolone or immunomodulatory treatments). QMG assesses MG severity and functional impact, with lower values indicating less severe disease.
“To further inform on the effectiveness and safety of rituximab as a first-line treatment agent in new-onset generalized MG, we recorded and analyzed long-term outcomes for the RINOMAX participants,” the researchers wrote.
Patients on rituximab had lower risk of needing rescue treatments
The follow-up study included the 46 trial participants who were alive approximately one year after the study began. They were followed for a mean of 4.9 years, with a maximum follow-up of 7.6 years.
Most participants initially assigned to the placebo (72.7%) received rituximab at some point, at an average of seven months from randomization. Most of those treated with rituximab (75%) received more than one treatment dose.
Patients were categorized into three groups: those who were originally allocated to rituximab (early rituximab; 25 people), participants initially treated with the placebo who switched to rituximab (delayed rituximab; 16 people), and those who were never exposed to rituximab.
Results demonstrated that QMG scores were significantly lower in participants treated with rituximab after one and two years, with similar trends up to five years, compared with the placebo group. A similar trend favoring rituximab was observed in the MG activities of daily living scale (MG-ADL), which assesses the impact of MG on a person’s daily life.
After adjusting for age at disease onset, sex, and previous rescue treatment, patients treated with rituximab showed a trend toward a 57% lower risk of hospitalization and 34% lower risk of needing rescue treatments.
When comparing the early and delayed rituximab groups, the delayed group received more rituximab doses than the early group (average of 5.9 vs. 3.6), with a median frequency of 1.1 and 0.7 doses per year, respectively.
Also, more participants in the delayed group received rescue treatments (50% vs. 25%), other immunosuppressants (31.3% vs. 16.7%), and were hospitalized due to worsening MG (56.3% vs. 20.8%). Still, only the latter difference reached statistical significance.
This indicates that early exposure to B cell-depleting therapies may be associated with better long-term outcomes.
Participants in the early rituximab group had significantly lower QMG scores for up to five years than those receiving delayed rituximab treatment, as well as significantly lower MG-ADL scores at one and four years, and a significantly lower prednisolone dose after one year.
After adjusting for age at disease onset, sex, and previous rescue treatment, the early rituximab group tended to show a 76% lower risk of hospitalization and 54% lower need for rescue therapy.
Moreover, Myasthenia Gravis Status and Treatment Intensity grades, which reflect symptom severity and intensity of immunosuppressive treatments, were significantly higher in the delayed group after two and three years.
These results are similar to those of a previous study in Sweden, which showed that starting rituximab within 12 months of gMG onset reduced time to disease remission and need for rescue therapy.
“This indicates that early exposure to B cell-depleting therapies may be associated with better long-term outcomes,” the researchers wrote, highlighting that “further studies are needed to shed light on the long-term benefit–risk balance with [rituximab] in generalized MG.”
Val
Hi. I live in the U.S. and I had my first dose of Rituxan in 2011 which was 13 years after I was diagnosed. I had been severely refractory and had basically been treated with every other option at that time including chemotherapy.
Jodi Enders
Hi Val, thank you for sharing your experience. During those years of trying different approaches, what part was hardest to carry emotionally?
-Jodi, Patient Advocate