Case Report: Eculizumab in highly active myasthenia gravis complicated by severe infections

Abstract

Highly active myasthenia gravis refers to a subset of refractory patients who exhibit recurrent exacerbations and crises. Eculizumab, a complement C5 inhibitor, has shown its efficacy and safety for patients with anti-acetylcholine receptor antibody-positive(AchR +)refractory generalized myasthenia gravis(gMG) in the REGAIN trial. However, the efficacy and safety of eculizumab in treating MG patients with severe infections have not yet been supported by clinical evidence. This is a case series reporting four patients with highly active myasthenia gravis complicated by severe infections. Changes in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores were recorded before and after 12 injections of eculizumab to assess efficacy. Pathogen characteristics of infections were summarized using bacterial culture and next-generation sequencing (NGS) results, presented as a heatmap to illustrate pathogen species and abundance. Inflammatory markers, including Procalcitonin (PCT), C-Reactive Protein (CRP), neutrophil count, and total lymphocyte count, were monitored to evaluate the safety. Treatment regimens were retrospectively analyzed to further assess clinical outcomes and safety. The baseline ADL data for the four patients was 22 ± 2.31 (Mean ± SD), and the baseline QMG data was 30.5 ± 8.23. After 12 injections of eculizumab treatment, the scores decreased to ADL 4.75 ± 3.3 and QMG 14 ± 3.37. During the treatment, no apparent worsening of infections related to Eculizumab was noted. Three patients successfully had their tracheostomy tubes removed, and none of the four patients experienced further myasthenic crises. Eculizumab demonstrated clinical improvement in this series, and the treatment was well-tolerated. This case series addresses the need for data on complement inhibitors in highly active myasthenia gravis patients with severe infections, provides clinical reference support for the expanded application of eculizumab.

Keywords: case series; complement inhibition; eculizumab; highly active myasthenia gravis; severe infections.

Figure 1

Baseline clinical features of the four myasthenic cases; Ab, antibody; MGFA class, Myasthenia Gravis Foundation of America Classification; ICU, Intensive Care Unit; MC, Myasthenic Crisis; Sex-M, Male; Sex-F, Female.

Figure 2

Heat map of pathogens encountered in the myasthenic patients; Case 1: Sputum culture results from the clinical laboratory of our center (The First Affiliated Hospital of Guangzhou University of Chinese Medicine) showed positive cultures for Klebsiella pneumoniae and Streptococcus pneumoniae. This patient did not undergo NGS testing. Since case 1 did not undergo NGS testing, her bacterial culture results are displayed with a yellow highlight mark (+). We collected all NGS test results performed during the treatment of Cases 2, 3, and 4 at our center. The details are as follows: Case 2: A total of 16 NGS tests were conducted from March 29, 2024, to November 8, 2024. Specimens included bronchoalveolar lavage fluid (BALF) and sputum.; Case 3: A total of 8 NGS tests were conducted from March 27, 2024, to September 15, 2024. Specimens included BALF and sputum; Case 4: A total of 7 NGS tests were conducted from January 18, 2024, to July 3, 2024. Specimens included BALF and sputum. Pathogen Analysis: In this report, we documented the bacterial, viral, and fungal pathogens detected in the NGS results of Cases 2-4, excluding suspected colonizing microorganisms and human microbiota. The left column summarizes the types of pathogens identified. For abundance comparison, we selected the highest reads count for each pathogen type from all test results for each patient and generated a heatmap.

Figure 3

Individual MG-ADL and QMG scores of the myasthenic patients during the 20 weeks period. During the maintenance phase, some QMG and MG-ADL scores were missing at specific injection time points. This was attributed to several factors, including patients returning to their local areas after discharge, transitioning to telephone follow-ups, or insufficient willingness to complete the assessments. Additionally, some patients opted for monthly assessments after consultation, resulting in missing data at certain injection time points. The “0” represents the baseline assessment score recorded prior to the initiation of eculizumab treatment.

Figure 4

Timeline of four patients’ disease and treatment process; : Time points of meningococcal vaccination in four Patients. The type of vaccine administered: ACYW135 meningococcal polysaccharide vaccine. :Onset time of the disease. ▼: Timing of disease progression and significant treatment. :Myasthenic Crisis (MC). :Impending Myasthenia crisis (IMC). DSP, Dexamethasone sodium phosphate pulse therapy. MPPT, Methylprednisolone pulse therapy. Efgartigimod administration: 1 cycle = 4 injections, once per week. The injection dose is calculated based on the patient’s body weight by 10 mg/kg. Unknown:For Case 2, the initial treatment details are unclear due to delayed diagnosis. For Case 4, the initial treatment details are unclear due to incomplete patient recall.