Complement C5 inhibition and neonatal Fc receptor modulation achieve similar outcomes in patients with myasthenia gravis, real world data indicate, however, the treatment effect is transient.

Researchers reported no significant difference between these two therapeutic mechanisms on the reduction of disease severity and symptom burden, in contrast to previous meta-analyses of clinical trial data.

Both strategies were also of benefit to treatment-refractory patients and had similar safety profiles, according to the paper, published in the Journal of Neurology, Neurosurgery and Psychiatry.

The authors note that prior analyses based on data from respective randomised controlled trials have so far generated heterogeneous results that favoured either neonatal Fc receptor modulation (FcRn) or complement C5 inhibition (C5IT) in patients with myasthenia gravis (MG).

However, in a propensity matched analysis involving 153 patients treated at eight specialist centres in Germany, both treatment strategies led to “rapid clinical improvements and substantial reductions in prednisolone doses”.

The study included data on 106 patients undergoing C5IT (n=26 eculizumab and n=80 ravulizumab) and 47 taking the FcRn inhibitor efgartigimod.

Direct comparison, which focused only on patients taking ravulizumab and efgartigimod, showed a reduction of 4.7 and 4.3 in the MG Activities of Daily Living (MG-ADL) score, respectively (p=0.637).

The maximum Quantitative MG score reduction was 5.4 for ravulizumab and 5.8 with FcRn inhibition (p=0.76).

The results also showed a comparable number of patients in both groups who met PASS (Patient Acceptable Symptom State) criteria, for MG-ADL (ravulizumab 28% vs efgartigimod 25%; p>0.999), QMG (50 versus 55%, respectively; p=0.823) and MSE (minimal symptom expression, 15% vs 13%; p>0.999).

The researchers also found no significant differences within the safety profiles of the two therapeutic strategies, except for a higher occurrence of cholinergic side effects in the ravulizumab group (23% vs 0%; p=0.0024).

However, the data showed that overall a significant proportion of patients had an insufficient response to these new treatment strategies (20%-49%).

The team highlighted several study limitations, including that the cohort was exclusively enrolled from tertiary centres in Germany.

Nevertheless, the study findings indicate that neither C5IT nor FcRn has superior efficacy or safety in patients with generalised MG in the real world setting.

“This study’s findings impact clinical practice by allowing personalised treatment plans based on the comparable efficacy and safety of C5IT and FcRn antagonists.

“It also highlights the need for new therapies and informed guidelines to address patients who do not respond adequately to existing treatments,” the authors stressed.

Place in the treatment pathway?

According to Dr John McConville, a Consultant Neurologist at the South East Health Trusts in Northern Ireland, the paper also mirrors previous observations that these drugs work quickly with clear improvement in the first month, but that their therapeutic effect “appears to plateau” over the following months.

“Their half-lives, expected mechanisms of action and these observations indicate that their treatment effect is transient and that their use does not obviate the need for medium- and long-term immunosuppression,” he said in a linked editorial.

Dr McConville argued that use of C5IT and FcRn antagonists should be considered similarly to human immunoglobulin therapy and plasma exchange in treatment algorithms.

“We should be aiming for minimal manifestations of MG on modest prednisolone doses with minimal use of these fast-acting therapies,” he said.

“Their use should prompt assertive early therapeutics in acetylcholine receptor antibody MG combining steroids with thymectomy in early-onset MG or rituximab in late-onset generalised MG, both therapies which have evidence of early efficacy and for sparing rescue therapy”.

Efgartigimod: first data

Meanwhile, a first look at real world evidence on use of efgartigimod in the UK has shown a treatment response in three-quarters of patients who received at least one cycle of the drug.

According to the data, from the first 48 patients with severe generalised MG to receive the drug in the country under the Early Access to Medicines Scheme, 75% experienced a mean reduction in the MG-ADL of at least 2 points.

The study authors, led by Dr Joana Moniz Dionísio, Department of Neurology, King’s College Hospital, noted that efgartigimod was well tolerated, with side effects generally mild and no rescue treatments required.

However, they noted that “further studies and ongoing real-world experience are required to determine which patients are most likely to respond to anti-FcRN treatment and where exactly it should fit in the treatment pathway for gMG”.