The 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2024) was held in Copenhagen, Denmark, from September 18 to 20, local time. Eight groundbreaking studies on Inebilizumab, an innovative drug licenced in by Hansoh Pharma, were selected for poster presentations at this year's conference, setting a new historical record.
Inebilizumab is the world's first approved humanized anti-CD19 monoclonal antibody for the treatment of adults with AQP4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD). It received market approval in China in March 2022, and in March 2023, it became the first NMOSD medicine included in the National Reimbursement Drug List.
China is one of the countries with the largest number of NMOSD patients in the world. With the support of new, highly effective biologics like Inebilizumab, Chinese experts have gained extensive clinical experience in treating NMOSD and produced a series of innovative research results with global significance. Of the eight innovative studies on Inebilizumab selected for poster presentations at this year’s ECTRIMS conference, four originated from China. These include key milestones, such as China’s first expert consensus on NMOSD monotherapy and the largest global real-world study on the use of Inebilizumab in NMOSD treatment. The academic contribution from China in the field of NMOSD will offer significant guidance for NMOSD treatment on a global scale.
Innovative Study 1
Inebilizumab treatment in Chinese Adult patients With AQP4-ab-positive Neuromyelitis Optica Specturm Disorder: A prospective study
Type: ePoster
No.: P1602
Author: Chao Quan ( Huashan Hospital, Shanghai Medical College, Fudan University, Department of Neurology, Shanghai, China)
Introduction：Neuromyelitis Optica Spectrum Disorder ( NMOSD ) is a rare autoimmune demyelinating condition of the central nervous system. In China, Inebilizumab, Satralizumab, and Eculizumab have been approved for NMOSD treatment, with Inebilizumab being the most widely used monoclonal antibody. However, its clinical usage still face challenges, developing comprehensive medication guidance would greatly benefit clinical practice.
Objectives/Aims: To develop validated recommendations for the clinical practice of inebilizumab in NMOSD through an evidence-based Delphi consensus, guiding clinicians in standardized medication practices.
Methods: An expert panel of clinicians with significant medication experience was formed to address frequent clinical queries. The method began with drafting recommendations through a literature review. Members voted on these, necessitating explanations for any dissent. The process allowed for three rounds of voting: the first required 100% agreement for immediate inclusion. Recommendations not unanimously approved were potentially revised after discussion for a second vote, aiming for a ≥90% consensus. If needed, a third round was held with the same consensus threshold. Final recommendations were those agreed upon across these rounds.
Results: A panel of 23 Chinese experts tackled ten pivotal NMOSD clinical questions, initially formulating 30 recommendations based on evidence. In the first voting round, 7 out of 30 recommendations didn ’ t achieve unanimous approval. The recommendations were revised based on objections, one similar recommendation was removed, and a new one was added. This resulted in a total of 30 expert recommendations by the second round, which satisfied the consensus criteria. These encompassed 4 on the use and timing; 13 on medication assessment, usage, and monitoring; 5 on drug switching, combination, and discontinuation considerations; 2 on safety management; and 6 on special population.
Conclusion: Based on evidence and clinical practice, expert guidance for inebilizumab use in NMOSD were established through an improved Delphi method. These guidelines will be valuable for standardizing clinical medication practices and optimizing patient outcomes.
Innovative Study 2
Inebilizumab treatment in Chinese Adult patients With AQP4-ab-positive Neuromyelitis Optica Specturm Disorder: A prospective study
Type: PaperPoster
No.: P308
Author: Wenjuan Huang ( Huashan Hospital, Shanghai Medical College, Fudan University, Department of Neurology, Shanghai, China)
Introduction：In March 2022, Inebilizumab (INEB) , a CD19 monoclonal antibody, was approved for the treatment of Adult patients with AQP4-ab-positive （AQP4＋） Neuromyelitis Optica Specturm Disorder (NMOSD) in China. But there is a paucity of real-world data, emphasizing the need for more cohort study.
Objectives/Aims: To estimate the efficacy and safety of INEB in a prospective population of Chinese adult patients with AQP4＋ NMOSD.
Methods: Adults (N=64) with NMOSD were enrolled from March 2023 to March 2024. The main outcome was annual relapse rate (ARR). Secondary outcomes were disability accumulation, assessed by the Expanded Disability Status Scale (EDSS) and the modified Rankin Scale (mRS), and adverse events (AEs).
Results: The majority of patients (92.1%, 59/64) were female, with a median age of onset at 33 (range: 18-71) years. The median follow-up time was 7.2 (rang: 0.4-12.6) months. INEB was the first maintenance treatment for 50% (32/64) patients. The mean ARR decreased significantly after treatment ( 1.94 vs 0.09; p＜0.001). By the end of March 2024, four patients had experience relapse. The time to first relapse ranged from 1.2 to 5.2 months, and one patient had two relapses during INEB treatment. There was a significant improvement in the median mRS score from 1.0 (range: 1.0 -5.0) to 1.0 (range: 0.0-2.0; p=0.021) . The median EDSS scores showed a downward trend from 2.5 (range: 1.0 -7.5) to 2.0 (range: 0-4.0) after INEB treatment; however, this reduction did not reach statistical significance (p=0.051). Over half of patients (59.3%, 38/64) reported adverse events (AEs) during treatment. Nearly half patients (45.3%, 29/64) developed mild injection-related reactions. Infections were seen in 23.4% (15/64) patients, of which 5 cases were severe infections requiring hospitalization or intravenous antibiotic therapy. Three patients developed pneumonia due to yeast, pneumocystis, and COVID-19, respectively. No deaths were observed. Three patients stopped treatment (two due to pneumonia and one due to relapse). Serum AQP4-ab are measured every six months, and 45.4% (10 out of 22) reported a decrease in titers after six months of treatment.
Conclusion: INEB significantly reduces relapse rates, improves mRS scores in patients with AQP4＋ NMOSD. Further prospective and comparative study are needed to reveal the long-term efficacy and safety of INEB.
Innovative Study 3
The Risk of Hepatitis B and Tuberculosis Reactivation in Patients with Neuromyelitis Optica Spectrum Disorder Treated with B-Cell Depletion Therapy
Type: ePoster
No.: P1069
Author: Rui Li ( The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China)
Introduction：There are no guideline recommendations for the prophylactic use of antiviral or anti-tuberculosis treatment for patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) who have latent hepatitis B virus infection or latent tuberculosis infection (LTBI) and are undergoing B-cell depletion therapy. Data on hepatitis B reactivation (HBVr) or tuberculosis reactivation following B-cell depletion therapy in such patients is urgently needed.
Objectives/Aims: This study aims to evaluate the incidence of hepatitis B or tuberculosis reactivation in NMOSD patients with potential hepatitis B infection or LTBI undergoing B-cell depletion therapy, providing evidence-based medicine evidence for clinical decision-making.
Methods: We selected NMOSD patients treated with either inebilizumab or rituximab monotherapy at the Third Affiliated Hospital of Sun Yat-sen University from 2016 to the present. At each treatment session, we conducted Interferon Gamma Release Assays (IGRA) , liver biochemistry, and hepatitis B virus serology tests. If hepatitis B core antibody (anti-HBc) conversion or active hepatitis was found, HBV-DNA was tested to determine HBVr; if IGRA was positive (indicating LTBI) , tuberculosis reactivation was assessed based on clinical and radiological evidence.
Results: Among the 56 NMOSD patients included in the analysis (27 treated with inebilizumab and 29 with rituximab) , the median follow-up time was 8 months (range 0.5-78). 28 patients (50%) were anti-HBc positive (latent hepatitis B infection) , of which 6 received prophylactic antiviral treatment against hepatitis B. The remaining did not undergo such treatment, and HBV-DNA was negative without any evidence of active hepatitis. Among the 9 patients with LTBI, only 1 received prophylactic anti-tuberculosis treatment, and no evidence of active tuberculosis was found in any of the patients.
Conclusion: NMOSD patients with potential hepatitis B infection or LTBI undergoing B-cell depletion therapy may not routinely require prophylactic antiviral/anti-tuberculosis treatment. Regular monitoring of relevant indicators, and initiating targeted treatment promptly upon evidence of hepatitis B/tuberculosis reactivation, may be a reasonable approach.
Innovative Study 4
AQP4 ‐ IgG Positive NMOSD with Polyglandular Autoimmune Syndromes Ⅲ : A Case Report
Type: ePoster
No.: P1749
Author: Huiru Xue (First Hospital of Shanxi Medical University, Department of Neurology, China)
Introduction：Polyglandular autoimmune syndromes (PAS) are multifactorial diseases with at least two coexisting autoimmune-mediated endocrinopathies, increasing the risk for various non-glandular autoimmune diseases like vitiligo, alopecia areata, autoimmune atrophic gastritis, Sjogren’s syndrome, myasthenia gravis and multiple sclerosis. There have been no reports of PAS combined with Aquaporin 4 autoantibody-positive (AQP4＋) Neuromyelitis Optica Spectrum Disorder (NMOSD) patients to date.
Objectives/Aims: To describe a 23-year old male diagnosed with AQP4-IgG + NMOSD and PAS.
Methods: We recorded the patient’s demographics, examination outcomes, radiological findings, whole exome sequencing results, human leukocyte antigen (HLA) genotyping, diagnosis, treatment and response to therapy.
Results: A 23-year old male presented with a history of vitiligo since age 8, thalassemia at 15, and type 1 diabetes mellitus (T1DM) at 16. At 19, he experienced hypoalgesia below the umbilicus post-cold, with magnetic resonance imaging (MRI) showing T8 to T10 abnormalities. At 23, folloing a fever, he suffered from vomiting and declining eyesight with MRI indicating optic nerves and periventricular abnormalities. Lab tests showed elevated TSH, TgAb, TPOAb levels, and ultrasound revealed thyroid nodules. CSF analysis indicated slightly elevated protein, and white blood cells, with AQP4 ‐ IgG at 1:100+ positive, GFAP ‐ IgG at 1:32+ positive, and GAD ‐ IgG at 1:100+ positive. Serum analysis showed AQP4 ‐ IgG at 1:320+ positive. CSF metagenomic next- generation sequencing (NGS) and family Trio-WES excepting thalassemia, identified no significant mutations. HLA genotyping was diagnostically value. The patient was diagnosed with NMOSD, PAS Ⅲ (autoimmune thyroid disease, T1DM, vitiligo) and thalassemia. After high-dose intravenous methylprednisolone and inebilizumab, his vision improved. Half a year later, no recurrence was observed, and his conditions were well managed. Besides, AQP4 ‐ IgG was 1:32+ positive and GFAP ‐ IgG was negative in serum.
Conclusion: In this case, the patient presented with optic neuritis, myelopathy, vitiligo, anemia, T1DM, and thyroid nodules diagnosed with AQP4 IgG+ NMOSD and PAS III. Following treatment with high-dose intravenous methylprednisolone and inebilizumab, the patient was monitored for over six months, resulting in satisfactory outcomes with no recurrence.
