New insights in managing myasthenia gravis in the clinic: what do you need to know?

Myasthenia gravis (MG) management is evolving rapidly, with new guidance and emerging targeted therapies changing clinical practice across the UK.

In this webinar, Professor Saiju Jacob, consultant neurologist at the University Hospitals Birmingham, and Dr Channa Hewamadduma, consultant neuromuscular neurologist and honorary senior lecturer at University of Sheffield and Sheffield Teaching Hospital, highlighted the key updates from the new Association of British Neurologists (ABN)guidance and the latest evidence on use of early, low-dose rituximab.

Updated guidance for MG management in the UK

The latest ABN guidelines on MG management were published in 2025, as an update from the previous 2015 document. Saiju explained it was intended for general neurologists, and was based on the current evidence base.

“Where there is no clear evidence available, we have used consensus expert review to help and guide the management,” he added. In his view, the most important part of the advice is an emphasis on specialist review. “If in doubt, call for help; speak to a friend,” he added.

One important update from the 2015 document is the specified treatment goal of minimal symptom expression (MSE), defined as an MG Activities of Daily Living (MG-ADL) score of zero or one, with a prednisolone dose of <5 mg to 7.5 mg a day, either with or without immunosuppressants.1

“Just having no symptoms is not enough,” said Saiju, “one of the major burdens of MGmanagement is steroid side effects, so we want to make sure patients are on as low a dose aspossible.”

Referral to, or discussion with, an MG specialist clinic should be considered if treatment goals are not achieved “within three months or so,” or in patients with complex disease, he added.1

Targeted therapies

The guideline recommends the use of targeted therapies, predominantly neonatal Fc receptor (FcRn) inhibitors and complement inhibitors, in treatment-resistant MG. All patients being considered for a targeted therapy, it goes on, should be referred to a specialist clinic or multidisciplinary team (MDT).1

Targeted therapies act on the MG pathogenesis at the neuromuscular junction, Saiju explained. FcRn inhibitors target the endothelial cells, while complement inhibitors target the post-synaptic membrane. Other novel immunotherapies include cytokines and chemokines, which act on the T-cells, plasma cell inhibitors, and B-cell inhibitors.

The FcRn rozanolixizumab is currently the only NICE-recommended treatment for uncontrolled generalised MG (gMG), and is indicated as an add-on therapy to standard treatment, Saiju explained. It can only be used in cases of AChR- or MuSK-positive, Myasthenia Gravis Foundation of America (MGFA) class 2 to 4a disease which is still uncontrolled after two or more treatments (excluding acetylcholinesterase inhibitors), and where IVig or PLEX would have otherwise been offered or has previously failed or been poorly tolerated.

The treatment landscape, however, is rapidly evolving. “Ten years ago, we had nothing other than azathioprine and mycophenolate, and now you cannot fit the number of drugs we have in MG on a single slide,” said Saiju. “This is exciting news for patients and clinicians treating myasthenia.”

Early, low-dose rituximab in gMG

The guideline also states that the evidence now supports the early use of the B-cell inhibitorrituximab,1 which, Channa explained, could help patients reach the specified treatment goals of MSE and minimal steroid use.

RINOMAX was a phase 2b randomised controlled trial of a single 500 mg rituximab infusion in new-onset (<12 months from diagnosis) generalised AChR MG. A total of 25 patients received rituximab, and 22 received placebo.3

At 16 weeks, 71% of those in the rituximab arm and 29% of those in the placebo arm had reached MSE, which was defined as a Quantitative Myasthenia Gravis (QMG) score of <4. While MG-ADL change at 16 weeks and QMG change at 24 weeks were not significant, the study provided “proof of concept” that a single 500 mg rituximab infusion could modify early disease course, said Channa.

Real-world, UK evidence

Rituximab, while not formally recommended for MG by NICE, has been approved for refractory cases through a specialised commissioning policy, by NHS England. As such, it has been delivered to eligible patients through commissioned centres with mandatory outcome dataset reporting since 2018.

Using data from these centres, researchers set out to understand the efficacy and safety of low-dose rituximab when administered within the first 12 months of MG onset, in a cohort designed to replicate that of RINOMAX. The analysis included 52 patients from eight centres from across England, Scotland, and Wales. The most common reason for commencing rituximab (32%) was the inability to wean the patient off prednisolone, while 16% cited explosive onset.

Of the 36 patients who experienced a reduction in MG-ADL, the mean reduction was -3.7points at three months, which was sustained up to 18 months. Channa highlighted that a ≥2 point reduction was considered the minimal significant improvement.

There was a steep drop in the median prednisolone dose, from 40 mg at baseline to 20 mg at three months. At 12 months, this figure was 5 mg. “This is a significant impact on patients’ lives,” said Channa.

At three months, 24% of patients had achieved MSE, a figure that increased to 70% by 18 months.

The study also found a favourable safety profile. Fifteen per cent of patients experienced an adverse event (AE), with the majority being mild infusion-related reactions. One patient (3%) experienced a serious AE, which was pneumocystis pneumonia.

In conclusion, he said that low-dose, early rituximab can help clinicians to achieve the treatment goals set out in the ABN guidelines by providing sustained symptom control and reducing steroid use.