Efgartigimod associated with improved daily function in 21 adults with generalized myasthenia gravis; immune findings limited to one patient

A retrospective study of 21 adults with acetylcholine receptor antibody-positive generalized myasthenia gravis found that efgartigimod treatment was associated with improved daily functioning during the first 12 weeks. The study also included exploratory immunological analyses of paired blood samples from one patient; those findings provide hypothesis-generating evidence and cannot establish a causal effect.

The clinical cohort was enrolled at the Second Affiliated Hospital of Harbin Medical University between March 1, 2024, and January 30, 2026. Eligible participants were adults with confirmed generalized myasthenia gravis, positive acetylcholine receptor antibodies and receipt of at least one efgartigimod cycle. Patients with anti-MuSK or anti-LRP4 antibodies, triple seronegative disease, conditions that could confound efficacy assessment, severe psychiatric or cognitive disorders, or incomplete data or follow-up were excluded.

At treatment initiation, five patients were classified by the Myasthenia Gravis Foundation of America as class II, 12 as class III and four as class IV. Five had thymoma, including three who had undergone thymectomy. All 21 had received pyridostigmine, while four were receiving an immunosuppressive drug: prednisone in one patient and tacrolimus in three.

Efgartigimod was administered intravenously at 10 mg/kg once weekly for four consecutive weeks. A second cycle began one month after the first, and subsequent cycles were given at variable intervals according to disease activity, maintenance of clinical benefit and shared physician-patient decision-making. Clinical efficacy was assessed with the Myasthenia Gravis Activities of Daily Living scale, or MG-ADL. Clinically meaningful improvement was defined as a reduction of at least two points from baseline, while minimal symptom expression was an MG-ADL score of zero or one. Concomitant symptomatic and immunosuppressive treatments could change during follow-up, including corticosteroid tapering.

Median MG-ADL scores declined from 7.0 at baseline, with an interquartile range of 6.0–8.0, to 3.0 at week 4 among 21 patients, 2.0 at week 9 among 20 patients and 1.0 at week 12 among 19 patients. Follow-up scores were significantly lower than baseline at every assessed visit, with all Holm-adjusted p values below 0.001. Two patients did not complete both cycles: one discontinued after an insufficient clinical response, while the other stopped after achieving minimal symptom expression and chose not to receive further efgartigimod.

After the first treatment cycle, 18 of 21 patients, or 85.7%, achieved clinically meaningful improvement, and 12 of 21, or 57.1%, had a reduction of at least five MG-ADL points. By the end of the second cycle, 18 of 19 evaluable patients, or 94.7%, met the clinically meaningful improvement threshold, and 16 of 19, or 84.2%, achieved the five-point reduction. At week 12, 14 of 19 evaluable patients, or 73.7%, had minimal symptom expression.

Treatment was generally well tolerated. Two treatment-related adverse events were reported: one case of low-grade fever and one case of herpes simplex infection. Both resolved within three days, treatment continued after resolution, and no serious adverse events occurred. In the single patient receiving prednisone, the dose decreased from 20 mg per day during the initial follow-up period to 15 mg per day by week 12, with continued efgartigimod treatment and stable clinical status; this case alone does not establish a general steroid-sparing effect.

The exploratory immune substudy used paired peripheral blood mononuclear cell samples from one 72-year-old participant collected before treatment and after six months of repeated treatment. He received two standard cycles followed by maintenance treatment every two to three weeks, totaling 14 infusions. His MG-ADL score fell from 6 at baseline to 1 after the second cycle and remained stable. After quality control, 25,272 cells were analyzed and classified into six major cell types and 13 subtypes. After treatment, monocytes decreased and natural killer cells increased, while effector-memory CD4-positive and CD8-positive T-cell populations showed slight upward trends.

Transcriptional and functional analyses suggested reduced inflammatory activity in myeloid cells after treatment. Downregulated gene pathways included NF-κB, interleukin-6, tumor necrosis factor, interleukin-12, interleukin-23 and type I and II interferon signaling, as well as antigen processing and presentation, chemotaxis, leukocyte migration, phagocytosis and Fc receptor signaling. Predicted intercellular communication also shifted: inflammatory and chemotactic pathways including MIF, CCL, interleukin-6 and VISFATIN had lower inferred information flow, while TGF-β and BTLA signaling increased. Natural killer cells showed greater incoming communication and transcriptional enrichment in pathways related to cell killing and innate immune responses.

T-cell and B-cell receptor sequencing indicated a more dispersed clonal architecture after treatment. The proportion of large clones increased, the proportion of small clones decreased, and extremely expanded clones with a size above 2,500 decreased; descriptively, the repertoire shifted from oligoclonal dominance toward more distributed expansion. Clonal expansion was concentrated mainly in effector T-cell subsets, including CD8 GZMB, CD4 CTL and CD8 GZMK cells. The B-cell receptor results showed a similar shift, while isotype distribution remained broadly stable, with no clear evidence of class-switch recombination. These immune findings came from one patient without biological replication, so individual temporal variation, technical variability and possible batch effects cannot be excluded. The investigators also did not perform antigen-specific analyses and could not directly assess changes in acetylcholine receptor-specific B cells. They characterized the results as exploratory rather than proof that efgartigimod caused the cellular changes.

Subject of Research: Real-world effectiveness and safety of efgartigimod in acetylcholine receptor antibody-positive generalized myasthenia gravis, with exploratory single-patient immune profiling

Article Title: Real-world clinical effectiveness and exploratory longitudinal immunological changes of Efgartigimod in myasthenia gravis: a retrospective study and a single-cell analysis in one patient

Article References: Tian, L., Zhang, L., Jin, J., Wang, X., Chen, Z., Qiao, L., Guo, Q., Li, Y., Zhang, J., Zhao, Y., Wang, L., Li, L., & Wang, J. (2026). Real-world clinical effectiveness and exploratory longitudinal immunological changes of Efgartigimod in myasthenia gravis: a retrospective study and a single-cell analysis in one patient. Frontiers in Neurology, 17, Article 1980412. https://doi.org/10.3389/fneur.2026.1980412

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1980412

Keywords: efgartigimod, generalized myasthenia gravis, retrospective cohort, MG-ADL, real-world evidence, single-cell RNA sequencing, immune repertoire, FcRn blockade, treatment safety, Real-world, clinical, effectiveness