The therapeutic armamentarium at the center of the article acts at different levels of the pathogenic cascade. The neonatal Fc receptor antagonists efgartigimod alfa and rozanolixizumab promote the degradation of circulating pathogenic IgG antibodies, giving them a rapid onset of action and a favorable safety profile. Ravulizumab, a long-acting terminal C5 complement inhibitor, acts downstream by preventing formation of the membrane attack complex and complement-mediated injury at the postsynaptic membrane; the CHAMPION MG trial confirmed rapid and lasting improvement in acetylcholine receptor antibody-positive generalized myasthenia gravis with maintenance dosing every eight weeks. Rituximab, by contrast, acts upstream by depleting CD20-positive B cells and may provide long-term immunosuppressive effect; in the RINOMAX randomized trial, rituximab given within twelve months of diagnosis increased the probability of achieving minimal disease manifestations and reduced the need for rescue treatment compared with placebo.

The Athens team retrospectively described seven purposively selected adults managed between February 2025 and July 2026, distinguishing therapies that had actually been administered from those merely planned at the data cutoff. Treatment selection was guided by disease severity, corticosteroid-related risks, presence of thymoma, comorbidities, peripheral venous access, vaccination requirements and the need for rapid improvement or sustained disease management. During the study period, efgartigimod alfa and rozanolixizumab were the only FcRn antagonists and ravulizumab the only C5 complement inhibitor commercially available in Greece, a practical constraint that shaped the pathways. Follow-up under the targeted strategy ranged from one to twelve months, and no treatment-related side effects, relevant infections or rescue therapies for worsening disease were recorded.

Three of the cases involved recent-onset disease, defined as diagnosis within the preceding twelve months. A 72-year-old man with a four-month history and advanced chronic glaucoma, for which corticosteroid escalation was contraindicated, received four cycles of efgartigimod alfa as a rapidly acting bridging therapy; prednisolone was halved from 15 to 7.5 milligrams per day while clinical stability was maintained, and rituximab was planned as the longer-term non-steroidal strategy. A 71-year-old man with recently diagnosed early-stage prostate cancer and hypertension received two cycles of rozanolixizumab, whose subcutaneous route was clinically practical, with prednisolone reduced from 15 to 12.5 milligrams per day while he completed the vaccinations required before planned rituximab. A 59-year-old man with type 2 diabetes and cardiovascular comorbidities worsened by steroids received a single efgartigimod cycle and reached a Myasthenia Gravis Activities of Daily Living score of 0, with prednisolone reduced from 20 to 17.5 milligrams per day.

A fourth profile involved very-late-onset disease, defined as onset at age 65 or older. An 80-year-old man with two months of predominantly bulbar dysfunction requiring a nasogastric tube received prednisolone, intravenous immunoglobulin and two rituximab infusions of 500 milligrams each, achieving enough improvement to remove the tube. Because dysarthria and dysphagia persisted and his peripheral venous access was poor, rozanolixizumab was initiated nine weeks after the second rituximab infusion as continuing, symptom-guided FcRn inhibition with the practical advantage of subcutaneous administration. After four cycles with intercycle intervals of three to six weeks determined by clinical need, his status improved from class IIIB to IIB, prednisolone fell from 10 to 7.5 milligrams per day, and immunophenotyping six months after rituximab showed CD19-positive cells at 0.5 percent, confirming sustained B-cell depletion.

Two thymoma-associated cases illustrate the bridging logic most vividly. A 46-year-old woman referred eighteen months after diagnosis with severe ocular-cervical-bulbar weakness received prednisolone, intravenous immunoglobulin, plasma exchange and four weekly rituximab infusions, yet disabling neck flexor weakness, nasal speech and dysarthria persisted. Efgartigimod was started eleven months after the rituximab course; after three cycles at seven-week intervals, prednisolone was reduced from 20 to 10 milligrams per day, and ravulizumab was intended as long-term therapy once required vaccinations were completed. A 48-year-old woman whose thymoma was removed incidentally, and who also carried a history of HPV-associated cervical adenocarcinoma, had poor venous access that precluded further plasma exchange; two efgartigimod cycles improved her from class IVB to IIA with an MG-ADL score of 1, while meningococcal vaccination proceeded toward planned ravulizumab. The choice is supported by growing real-world evidence, including an Italian multicenter ravulizumab cohort of 14 thymoma patients showing greater early Quantitative Myasthenia Gravis response in this subgroup, and a separate cohort of 23 patients confirming complement inhibitor effectiveness in thymoma-associated disease.

The seventh case involved chronic, corticosteroid-dependent disease with prominent ocular relapse. A 71-year-old man with a seven-year history had achieved pharmacological remission on mycophenolate mofetil and low-dose alternate-day prednisolone, then developed an unprovoked ocular-bulbar relapse with severe bilateral ptosis and diplopia. Prednisolone was raised to 25 milligrams per day, and symptom recurrence during tapering indicated inadequate control despite mycophenolate. Three efgartigimod cycles improved his MG-ADL score from 7 to 2 and his class from IIIB to IIB, but residual ptosis tended to recur as each cycle approached, precluding steroid reduction. Ravulizumab was therefore planned for sustained control, a rationale reinforced by a post hoc analysis of CHAMPION MG showing benefit across individual MG-ADL items, with particularly notable improvements in ocular symptoms including eyelid ptosis and diplopia.

The article also highlights practical pharmacology that determines sequencing. Clinically meaningful improvement with efgartigimod may appear as early as one week after the first administration, with maximal benefit generally around week four, while rozanolixizumab improvement has been detected from day eight, the first post-baseline assessment. FcRn antagonists require no pre-treatment vaccinations, allowing immediate initiation, whereas C5 complement inhibition demands meningococcal vaccination against serogroups A, C, W, Y and B completed at least two weeks before the first ravulizumab dose, with antibacterial prophylaxis required if treatment must begin sooner. This vaccination delay is precisely why FcRn antagonists served as immediately available bridging therapies in the thymoma and relapsing cases. For planned rituximab transitions, the team uses an interval of at least two to three weeks after the last FcRn dose, reflecting efgartigimod pharmacokinetics and serum IgG recovery preferably above 5 grams per liter, while stressing that no evidence-based interval has been established.

A subtle pharmacokinetic consideration runs through the discussion: because FcRn inhibition enhances IgG catabolism and ravulizumab is an IgG-based monoclonal antibody, FcRn blockade increases ravulizumab clearance, which is why the pathways were sequential rather than concomitant. Japanese clinicians have recently reported two refractory patients treated with combined subcutaneous efgartigimod and zilucoplan, a macrocyclic peptide C5 inhibitor that, not being an IgG antibody, escapes FcRn-mediated catabolism; zilucoplan was not commercially available in Greece during the study period. The authors are candid about limitations, including the retrospective single-center design, very small and heterogeneous sample, potential selection bias and the fact that several planned transitions had not yet been implemented, making the observations descriptive and hypothesis-generating rather than proof of comparative efficacy. Still, the seven pathways assign distinct but complementary clinical roles to each agent, rapid IgG reduction, long-term B-cell depletion and sustained terminal complement inhibition, and argue that treatment sequence should be tailored to disease phenotype, therapeutic objective, comorbidities, vaccination requirements and route of administration, with prospective studies needed to establish optimal intervals and biomarkers capable of guiding individualized selection.

Subject of Research: Neurology

Article Title: Individualized sequencing of targeted immunotherapies in generalized myasthenia gravis across distinct patient profiles

Article References: Zouvelou, V., Tzavella, D., Strataki, E., & Vakrakou, A. G. (2026). Individualized sequencing of targeted immunotherapies in generalized myasthenia gravis across distinct patient profiles. Frontiers in Neurology, 17, Article 1989043. https://doi.org/10.3389/fneur.2026.1989043

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1989043

Keywords: myasthenia gravis, immunotherapy, FcRn antagonists, rituximab, ravulizumab, neuromuscular disorders, targeted therapy, Individualized, sequencing, targeted, immunotherapies, generalized