We conducted a retrospective, observational study of patients with gMG treated with efgartigimod at two neuromuscular centers: the Cyprus Institute of Neurology and Genetics (Nicosia, Cyprus) and First Department of Neurology, University of Athens. The study period spanned from April 2023 to August 2025.

Eligible patients were adults (≥ 18 years) with a confirmed diagnosis of generalized myasthenia gravis according to established criteria. Only acetylcholine receptor (AChR) antibody–positive cases, consistent with the approved indication for efgartigimod by the European Medicines Agency, used as add-on therapy to standard care, were included (16). While MG-Activities of Daily Living (MG-ADL) thresholds were applied as inclusion criteria in pivotal clinical trials, the approved indication does not include a specified minimum MG-ADL score. Patients with isolated ocular MG, MuSK-positive MG, or seronegative MG were not treated with efgartigimod at these centers. Patients were eligible for efficacy analyses if they had at least one treatment cycle with available MG-ADL assessments both before and after efgartigimod administration.

Efgartigimod was administered intravenously at a dose of 10 mg/kg once weekly for four consecutive weeks (one treatment cycle), in accordance with the approved regimen. In routine clinical practice, the timing of subsequent cycles was individualized and determined by the treating clinician based on the patient’s clinical status and practical considerations, including intercurrent infections or comorbidities. Accordingly, additional cycles were administered at variable intervals as part of observational, real-world care rather than according to a prespecified or protocolized retreatment schedule.

Data were extracted from medical records, including: (a) Demographics: sex, age at efgartigimod initiation, and disease duration, (b) Clinical severity: Myasthenia Gravis Foundation of America (MGFA) class at baseline and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores immediately before and after each cycle. (c) Immunological markers: baseline AChR antibody positivity in all patients; follow-up AChR titers (measured by radioimmunoassay, RIA) and total IgG levels when available. (d) Corticosteroid therapy: daily prednisolone-equivalent dose before and after each cycle and at the most recent follow-up. (e) Concomitant immunosuppressive therapy: use of oral agents such as azathioprine or mycophenolate mofetil, including whether treatment was continued, discontinued or initiated. (f) Treatment exposure: number of cycles, interval between cycles, total duration of follow-up, and reasons for discontinuation, and (g) Safety: infections, infusion-related reactions, and other adverse events occurring during treatment.

The analysis included two predefined populations to distinguish efficacy evaluation from overall treatment exposure. (a) Primary Efficacy Set (PES): all patients and treatment cycles with baseline (pre-cycle) MG-ADL ≥ 2, to minimize floor effects and capture clinically meaningful change. (b) Full Analysis Set (FAS): all 13 treated patients (and their cycles) with any available MG-ADL data, irrespective of baseline score. Cycles starting at MG-ADL = 0 or 1 were excluded from the primary efficacy analysis because a ≥ 2-point improvement cannot occur from that baseline. These were analyzed separately as maintenance, corticosteroid-sparing, or bridging treatments, reflecting preservation of minimal-symptom status rather than absence of efficacy.

Primary outcome was considered the change in MG-ADL score from pre- to post-cycle within the PES. Secondary outcomes were: (a) Responder rate (≥ 2-point MG-ADL improvement from pre- to post-cycle) analogous to the responder definition used in ADAPT; (b) achievement of minimal-symptom expression (MSE), defined as MG-ADL 0–1, as defined in ADAPT+; (c) corticosteroid-sparing effect, assessed as (i) per-cycle change in prednisone-equivalent dose and (ii) overall change from baseline to the latest follow-up; (d) changes in total IgG and AChR-antibody titers, where available; and (e) safety outcomes: infections, infusion reactions, and treatment discontinuations.

Continuous variables were summarized as mean ± SD or median (IQR), and categorical variables as counts (%). Per-cycle MG-ADL changes were primarily evaluated descriptively using medians and interquartile ranges, while overall within-patient change from baseline to the latest follow-up in the PES was additionally assessed using paired t-test. Changes in total IgG and AChR-antibody levels before and after each cycle were analyzed using the Wilcoxon signed-rank test for paired comparisons. Associations between the magnitude of total IgG or AChR-antibody reduction and MG-ADL improvement were examined using Pearson’s (r) and Spearman’s (ρ) correlation coefficients. Responder rates (≥ 2-point improvement) and achievement of minimal-symptom expression (MG-ADL 0–1) were expressed as percentages. Given the small sample size, analyses were primarily descriptive, with inferential tests performed on an exploratory basis.

A total of 13 patients with AChR-antibody–positive gMG received at least one efgartigimod treatment cycle between April 2023 and August 2025. All were included in the Full Analysis Set (FAS). The Primary Efficacy Set (PES) comprised 10 patients who had at least 1 cycle with baseline MG-ADL ≥ 2 (Figure 1). Three patients were treated exclusively during periods of minimal-symptom expression (baseline MG-ADL 0–1), such as maintenance or bridging treatment. In total, the cohort contributed 52 treatment cycles.

While most patients followed the standard regimen of four weekly infusions per cycle, one received a modified intermittent schedule consisting of two consecutive weekly infusions followed by a one-week pause—occasionally extended to 2 weeks during 1 cycle. This individualized, clinician-driven approach aimed to maintain clinical stability and convenience while minimizing treatment burden. The interval between cycles was defined as the time from the start date of one efgartigimod cycle to the start date of the subsequent cycle. Across the cohort, the median start-to-start interval was 9 weeks (IQR 7–11; range 6–29). Two patients permanently discontinued efgartigimod during follow-up: one due to gradual attenuation of treatment effect over successive treatment cycles and another one following a new diagnosis of malignancy, deemed unrelated to efgartigimod, with treatment discontinued to initiate oncologic management. Baseline demographics and clinical features are summarized in Table 1.

At baseline, disease severity according to the MGFA classification ranged from class IIIa to IVb. Most patients (9/13) were classified as MGFA III (six IIIb and three IIIa), while one patient had class IVb disease. Three patients had MSE (MG-ADL 0–1), reflecting minimal disease activity at baseline; therefore, MGFA classification was not applied.

Efgartigimod was most commonly initiated (in eight patients) in the setting of incomplete disease control despite corticosteroids and conventional immunosuppressive therapies, and in some cases despite maintenance treatment with IVIG, or following non–life-threatening relapse with symptom recurrence. One patient received efgartigimod after secondary loss of response to ravulizumab. In two immunosuppressant-naïve patients with long-standing gMG and residual limb weakness accompanied by intermittent symptomatic fluctuations, efgartigimod was introduced as add-on therapy to pyridostigmine.

Among the three patients treated during periods of MSE, distinct clinical contexts were observed. In one young female patient, efgartigimod was administered in the peri-operative period prior to thymectomy. At that time, she was receiving high-dose oral prednisolone (55 mg/day), and efgartigimod was introduced to facilitate corticosteroid tapering to 20 mg/day while maintaining clinical remission, with the aim of reducing the risk of peri-operative complications associated with prolonged high-dose corticosteroid exposure. The remaining two patients had late-onset gMG and received efgartigimod as bridging therapy until the clinical effect of a non-steroidal immunosuppressive agent was established. One of these patients had experienced two severe, unprovoked exacerbations within the preceding 6 months, necessitating rescue therapy with IVIG and PLEX, respectively. In the other patient, long-term oral corticosteroid therapy was contraindicated because of severe osteoporosis; therefore, efgartigimod was selected as a temporary treatment option while awaiting the onset of action of conventional immunosuppression. In three patients with a history of extrathymic malignancy (two with refractory disease and one treated during MSE), efgartigimod was preferentially selected to avoid non-selective immunosuppression and to minimize the theoretical risk of cancer recurrence. Individual patient characteristics and treatment details are summarized in Supplementary Table S1.

At baseline, the median MG-ADL score across all patients (FAS; n = 13) was 6 (IQR 2–9; range 0–10). Within the PES (n = 10), the median baseline score was 7 (IQR 4–9). After excluding cycles initiated at MG-ADL 0–1, a total of 42 efficacy-evaluable cycles were analyzed. The median per-cycle MG-ADL change was −2 points (IQR − 4 to −2). A ≥ 2-point improvement was observed in 31 cycles (74%), stability (± 1 point) in 8 (19%), and worsening in 2 (5%), both from the same patient who exhibited late clinical fluctuation after repeated cycles. Across the treatment period, all PES patients achieved at least one ≥ 2-point MG-ADL improvement, and half (5/10) reached MSE during at least 1 cycle. From baseline to the latest follow-up, MG-ADL scores among PES patients decreased significantly, with a median overall change of −3 points (IQR − 5 to 0) and a mean reduction from 6.7 ± 2.4 to 4.3 ± 3.2 (t (9) = 2.58, p = 0.030). At the latest assessment, seven patients (70%) maintained lower MG-ADL scores compared with baseline, while three (30%) showed an increase of +2 points. Figure 2 illustrates individual MG-ADL trajectories across treatment cycles.

At baseline, 11 of 13 patients (85%) were receiving oral corticosteroids, with a median prednisolone-equivalent dose of 15 mg/day (IQR 10–22.5 mg). During follow-up, 9 of these 11 patients (82%) achieved a dose reduction, including one who successfully discontinued corticosteroids. Among those who tapered, the median decrease was 10 mg/day (IQR 5–15 mg), corresponding to an approximate 50% reduction from baseline doses. The final median daily dose across all steroid-treated patients was 10 mg (IQR 8.8–17.5 mg), while two patients (18%) were maintained on stable regimens without dose change. Figure 3 illustrates individual corticosteroid trajectories (prednisolone-equivalent doses) across treatment cycles.

At baseline, 4 of 13 patients (31%) were receiving concomitant oral immunosuppressive therapy in addition to corticosteroids—one on azathioprine (AZA) and three on mycophenolate mofetil (MMF). During efgartigimod treatment, doses remained stable in two patients, while azathioprine and mycophenolate were discontinued in two others because of lymphopenia and were not reinitiated. In one patient, efgartigimod was introduced to bridge the delayed onset of action of a newly started MMF.

Across all paired cycles (FAS, n = 34), total IgG levels decreased significantly after each efgartigimod cycle (median reduction 56.7%, IQR 44.5–65.3%; Wilcoxon p < 0.001), consistent with the expected pharmacodynamic effect of FcRn blockade. Within the PES (baseline MG-ADL ≥ 2; n = 25), the median per-cycle IgG reduction was 54.4% (IQR 39.2–65.9%; p < 0.001). The correlation between percent IgG reduction and MG-ADL improvement was weak and not statistically significant (Pearson r = 0.20, p = 0.34; Spearman ρ = 0.29, p = 0.16).

Paired acetylcholine receptor (AChR) antibody titers were available in 15 cycles and showed a significant overall decrease (median 52.4%, IQR 33.3–64.9%; Wilcoxon p < 0.001). Among PES cycles with both serological and clinical data (n = 7), changes in AChR antibody titers showed no significant association with MG-ADL improvement (Pearson r = −0.12, p = 0.79; Spearman ρ = −0.34, p = 0.46). Figure 4 illustrates individual trajectories of total IgG (Figure 4A) and AChR antibody levels (Figure 4B) across treatment cycles, respectively.

During follow-up, four patients (4/13; 31%) required temporary adjunctive therapy for episodes of clinical worsening managed outside the setting of myasthenic crisis. IVIG was administered on six occasions in four patients, and PLEX was performed twice in two patients, both of whom had previously received IVIG. These interventions were most commonly initiated in the context of intercurrent infections or prolonged intervals between efgartigimod cycles. In most cases, adjunctive therapy was associated with clinical stabilization. One patient with a highly treatment-refractory disease course required multiple adjunctive courses (two IVIG cycles and one PLEX) and subsequently discontinued efgartigimod because of lack of sustained overall clinical benefit.

Efgartigimod was overall well tolerated, with no treatment-related serious adverse events or infusion reactions. Mild to moderate infections occurred in 13 of 52 treatment cycles (25%), most commonly upper respiratory tract infections (n = 6) and lower respiratory tract infections (LRTI) (n = 3). In one case, a cycle was discontinued after the second infusion due to an LRTI requiring antibiotic therapy. One patient with chronic suprapubic catheter experienced recurrent urinary tract infections during two separate cycles, while another developed herpes zoster ophthalmicus after the third infusion of a cycle, resulting in prolonged antiviral therapy and postponement of the final dose. Other reported adverse effects included headache, myalgia, chills, and diarrhea in one patient. Overall, 6 cycles were postponed and one was stopped early due to intercurrent illness. All affected patients recovered fully, and none required hospitalization or permanent treatment discontinuation.

This study provides the first real-world analysis of efgartigimod use in Greece and Cyprus, drawing on detailed longitudinal data from two national neuromuscular referral centers. The availability of cycle-level MG-ADL assessments, corticosteroid dosing, and serological measurements enabled an integrated evaluation of clinical, pharmacodynamic, and treatment-pattern outcomes over time. Importantly, the pragmatic design—with individualized retreatment intervals, concomitant immunosuppressive use, and real-world management of clinical worsening—closely reflects routine clinical practice and enhances the clinical relevance of the findings.

Several limitations should be acknowledged. The retrospective, observational, and uncontrolled design, together with the small sample size, limits statistical power and generalizability. Only patients within the PES could be meaningfully assessed for MG-ADL improvement, as those treated during periods of MSE were analyzed separately for maintenance or steroid-sparing purposes. Serological data were not available for all treatment cycles, and background immunosuppressive regimens—including corticosteroid dosing—were heterogeneous and could change over time. MG-ADL was the sole clinical outcome measure; the absence of complementary quantitative assessments such as QMG or MG-Composite may have limited sensitivity to subtle changes in strength or endurance. In addition, sustained response duration as defined in ADAPT could not be systematically evaluated due to variable follow-up timing inherent to real-world practice. Differences in follow-up duration and retreatment intervals may also have influenced comparisons across cycles. Moreover, access to efgartigimod in Greece and Cyprus is subject to national reimbursement and approval procedures, which may have contributed to delays in treatment initiation and variability in retreatment timing. Despite these limitations, the study provides clinically meaningful insight into how FcRn blockade is applied and managed in everyday practice across diverse clinical scenarios.