Rescue Therapy With Rozanolixizumab Promising in Triple-Seronegative MG

Triple-seronegative myasthenia gravis (MG) responded following the administration of rozanolixizumab (Rystiggo; UCB) in a new study,¹ potentially offering hope for this subset of patients with the autoimmune disease. Still, the investigators of this study offer caution in extrapolating their results to a wider patient audience, as the patient at the center of their case study is a type not frequently included in clinical trials.

“The indication should be approached with caution,” they say.

A humanized immunoglobulin G4 antibody/neonatal Fc receptor antagonist, rozanolixizumab was approved in the US in 2023, Japan in 2024, and the European Union in 2025.² Previous research also demonstrates its ability to improve muscle weakness and fatigue. However, its strength has not been evaluated among patients who test negative for anti-acetylcholine receptor antibodies (most common), muscle-specific kinase antibodies (less common), and low-density lipoprotein receptor–related protein 4 antibodies (least common).^1,3

The 28-year-old patient at the center of this case report had triple-seronegative MG refractory following repeated treatment attempts with intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIg), and plasma exchange. This subtype of MG accounts for 10% to 15% of all MG cases, meaning this small group of patients is somewhat rare and frequently excluded from randomized controlled trials.

She presented with ptosis and diplopia, the former improved with edrophonium injection, a rapid-onset, short-acting, reversible acetylcholinesterase inhibitor,⁴ and ice-pack tests. Treatment with pyridostigmine was stopped, as it was not tolerated when administered for 2 weeks, and 2 courses of IVMP (1000 mg x 3 days) were implicated in her progression to generalized MG. There was also no demonstrable response to 1 course of IVIg (400 mg/kg x 5 days). Only after 2 more cycles of IVMP and 1 cycle of plasma exchange did the patient exhibit muscle strength and endurance improvements. Her disease was categorized as Myasthenia Gravis Foundation of America class IIIa.

Six months after her first plasma exchange, the patient showed a relapse in her muscle weakness and was hospitalized. Repeated nerve stimulation tests were positive, however, and repeated edrophonium and ice-pack tests showed improvement in ptosis and limb weakness. Eight weeks later, there was another exacerbation. At this point, due to her history of treatment failure, rozanolixizumab was given through a course of 6 weekly injections at 420 mg each.

The treatment protocol for the rescue therapy called for suspension if her immunoglobulin G levels dropped to below 1.0 g/L or fluctuated between 1.0 and 2.0 g/L and she had signs of infection. She completed 5 treatment cycles, all of which included 6 full doses of rozanolixizumab, and was clinically stable with no serious adverse events after the final cycle. Treatment is ongoing.

Noting that their treatment criteria mirrored the protocol from the MycarinG trial (NCT03971422), the authors explained that the patient’s intercycle intervals ranged from 3 to 7 weeks compared with 8 weeks seen in MycarinG. Still, the patient was able to achieve symptom control with no severe adverse effects: at baseline, her immunoglobulin G level was 6.7 g/L; her minimum precycle immunoglobulin G level was 3.9 g/L; and her lowest overall immunoglobulin G level was 1.0 g/L.

“Importantly, while rozanolixizumab significantly reduced IgG levels, IgA and IgM remained stable – unlike PLEX, which broadly depletes immunoglobulins,” the authors wrote. “This suggests that humoral immunity was preserved despite selective IgG depletion.”

They concluded that future studies of rozanolixizumab should include seronegative patients, due to the need for real-world evidence on treatment utility in patients who have MG.

References

1. Takenobu Y, Kikuchi T, Ishikawa D, et al. Rozanolixizumab as rescue therapy in triple seronegative refractory generalized myasthenia gravis. Immunol Med. Published online November 10, 2025. doi:10.1080/25785826.2025.2582274
2. Shaw M. MG Symptoms PRO highlights rozanolixizumab’s impact on fatigue, weakness. AJMC^®. August 22, 2025. Accessed November 18, 2025. https://www.ajmc.com/view/mg-symptoms-pro-highlights-rozanolixizumab-s-impact-on-fatigue-weakness
3. Shaw M. Understanding gMG: autoantibodies and life-altering muscle weakness. AJMC. January 17, 2025. Accessed November 18, 2025. https://www.ajmc.com/view/understanding-gmg-autoantibodies-and-life-altering-muscle-weakness
4. Edrophonium (injection route). Mayo Clinic. Updated July 1, 2025. Accessed November 18, 2025. https://www.mayoclinic.org/drugs-supplements/edrophonium-injection-route/description/drg-20075629