Rare "see" the dawn - Ruijin Hospital prescribes Quanxinda® (ofatumumab)

The struggle between human beings and disease is never-ending
.

For common diseases such as hypertension, diabetes, and cardiovascular disease, everyone is already familiar with them, and the social concern is also very high
.

Rare disease - currently defined as a disease with an incidence rate of less than 1/10,000, a prevalence rate of less than 1/10,000, and a disease population of less than 140,000; perhaps there are many terms in it that ordinary people have never even heard of, but they are indeed troubled and tortured With this very small part of the sick population, it should not be ignored
.

In the neurology department of a large tertiary hospital, the struggle against rare and difficult diseases has become "normal"
.

Rare diseases are often "difficult" because they are not well known
.

A few years ago, there were only a handful of rare diseases that could be correctly diagnosed and treated.
With the increasing emphasis on this special group in China, some of these diseases have been effectively treated
.

"Rare" see "Dawn"
.

Here, I will share with you the cases of rare neurological diseases that have been effectively treated.
I believe this number will gradually increase
.

Author: Chen Sheng (Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine) Mr.
Wang, a patient with lower limb numbness, is on the rise in his career.
He may not have imagined that he suffers from a rare neurological disease
.

In recent months, he has complained of numbness in his lower limbs and a feeling of being restrained in his chest
.

Went to the hospital for a check and found clues
.

There are many "sclerotic lesions" in his brain and spinal cord
.

This is not arteriosclerosis as we traditionally understand it, but multiple sclerosis
.

Multiple sclerosis (MS) is a rare immune-mediated disease characterized by inflammatory demyelinating lesions of the central nervous system
.

If you compare the long axons of neurons that transmit electrical signals to the wires in our body, the myelin sheath is the enameled wire wrapped around the wires, and its insulating effect is to maintain the conduction of electrical signals.
plays a vital role
.

When there is a problem with the immune system, these 'enameled wires' will be attacked, and then gradually damaged and lost, causing some neuropsychiatric symptoms, namely central nervous system demyelinating disease, which is like a 'wire short circuit'.
A series of 'disorders'
.

Multiple sclerosis mostly occurs in 20-40 years old, with insignificant early symptoms, slow progress, and easy misdiagnosis and missed diagnosis.
It is the most common non-traumatic disabling disease in young people
.

The early stage of the disease presents with recurrent and diverse clinical symptoms, including limb weakness, paresthesia, vision problems, ataxia, or cognitive impairment
.

When the nerve damage accumulates to a certain extent, the clinical symptoms will no longer be relieved, and the disease will slowly and continuously progress and deteriorate over time, which may eventually lead to serious consequences of blindness, disability, and loss of self-care ability
.

In order to monitor the demyelinating lesions in Mr.
Wang's brain more accurately and intuitively, we performed 18F-florbetapirPET/MRI quantitative visualization of myelin monitoring on him, and found that Mr.
Wang's brain lesions were heavily loaded and the demyelination was severe
.

If left untreated, the risk of later disability is extremely high
.

To make matters worse, Mr.
Wang also has kidney disease.
Most of the existing small-molecule drugs are metabolized by the liver and kidney, which is not suitable for him
.

We recommended ofatumumab to him and introduced the characteristics of the drug to him, ofatumumab is a fully human monoclonal antibody targeting CD20, which induces lysis and elimination of pathogenic B cells, It can more effectively control the recurrence of the disease and the progression of disability, and it does not undergo liver and kidney metabolism and has no liver and kidney toxicity, which is more suitable for his current situation
.

The approval of ofatumumab is based on the results of the Phase III clinical trial ASCLEPIOS study[i]
.

A total of 1,882 patients with relapsing multiple sclerosis were included in the study.
The results showed that compared with the active control group, ofatumumab significantly reduced new gadolinium-enhanced T1 lesions by 98%, and reduced new or enlarged T2 lesions.
85%, reducing the annual recurrence rate by 59% (the annual recurrence rate in the ofatumumab group reached 0.
1, which is equivalent to only one recurrence in ten years), and reducing the risk of disability progression by 34%, all of which were statistically significant
.

In the second year of ofatumumab treatment, 88% of patients achieved the composite index of no recurrence, no active disease, and no disability progression - NEDA-3 (no evidence of disease activity)[ii]
.

 Figure 1: Image summary from the ASCLEPIOS study showing almost complete clearance of gadolinium-enhanced (Gd+) T1 lesions with ofatumumab at 12 months
.

Oxford BDI Images pooled images from ASCLEPIOS stage III, gadolinium-enhanced (Gd+) T1 magnetic resonance imaging (MRI) of 314 newly diagnosed untreated patients at baseline and after 1 year of Quanxinda (images from 314 patients were pooled).
We believe that in the treatment of multiple sclerosis, time is the myelin sheath, and time is the brain and spinal cord.
For patients diagnosed with MS, high-efficiency disease-modifying therapy should be started as soon as possible to suppress the activity of the lesions as much as possible, reduce recurrence, and avoid Long-term disability progression
.

Especially for young patients, this has a big impact on their work and quality of life for decades to come
.

In harmonious communication, both doctors and patients reached a consensus on treatment
.

Fortunately, Mr.
Wang was the first to use this highly effective biological agent on the day of delivery on March 24
.

We all look forward to his speedy recovery
.

Fig.
2 Dr.
Zhou Qinming, the chief physician of the Department of Neurology, Ruijin Hospital, administered Quanxinda® (ofatumumab) injection for MS patients to treat two young children with muscle weakness.
In addition to multiple sclerosis, autoimmune encephalitis and other diseases, other rare, The treatment of difficult patients has always been the direction we stick to
.

In March 2022, at the height of the epidemic in Shanghai, a 29-year-old Fujian girl was troubled by long-term severe muscle weakness and scoliosis.
She traveled all the way from her hometown to seek medical treatment in Shanghai
.

This patient has been misdiagnosed as a muscle disease for a long time.
Director Zhou Haiyan, director of neuroelectrophysiology at Ruijin Hospital, confirmed that the patient had chronic neurogenic electromyography through EMG examination.
Combined with the medical history and physical examination, the diagnosis was a rare spinal muscular atrophy.
(SMA), final genetic testing confirmed the diagnosis
.

The discipline immediately set up a treatment team, and the green channel was admitted to the ward
.

After a thorough evaluation, we administered an intrathecal injection of antisense oligonucleotides to the young girl
.

Then we cooperated with the Rehabilitation Department to customize an individualized rehabilitation training program for the patient
.

Coincidentally, not long before, another young man suffered sudden respiratory failure and limb weakness and was rushed to Ruijin North Hospital, and underwent cardiopulmonary resuscitation and endotracheal intubation
.

Since the patient was young and critically ill, we immediately opened the green channel and conducted a multidisciplinary consultation
.

Ultimately, the patient was diagnosed with Pompe disease - a rare glycogen storage disorder
.

Without active intervention, the patient is likely to be paralyzed for life and rely on a ventilator for a living
.

We immediately formulated a specific drug for Pompe disease for patient treatment
.

The two rare disease patients are currently recovering, and may gradually regain their motor function and hope for life
.

Fig.
3 Dr.
Huang Pei, Department of Neurology, Ruijin Hospital, performed intrathecal injection for young SMA patients, said Professor Liu Jun, Director of the Department of Neurology of Ruijin Hospital: "Patients with difficult and rare diseases, including multiple sclerosis, should receive more and more attention.
, more new technologies and new drugs should go to the clinic to benefit these patients
.

" Rare disease patients should not be "abandoned" by society and "abandoned" by medicine
.

We need to do 100% of our efforts to develop new technologies and medicines to bring hope to these patients
.

We are also very happy to see that China is investing more and more in rare diseases, and more and more "orphan drugs" are entering the Chinese market faster and faster
.

The spring of "rare diseases" is bound to come
.

At the moment of the epidemic, we also hope that through our common persistence and perseverance, we will build a "Wall of Hope" for the majority of patients with difficult and rare diseases in neurology
.

Expert Profile Professor Chen Sheng Deputy Director of Neuroimmunology and Difficult Diseases Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Member of the Youth ALS Collaborative Group of the Neuroscience Professional Committee of the Chinese Research Hospital Association Member of the Youth Committee of the Neurology Branch of the Shanghai Medical Association The 4th Chinese Medical Doctor Association Outstanding Young Neurological Physician Lancet Reviewer was selected as Shanghai Young Top Talent, Shanghai Shuguang Researcher Ruijin Hospital Neurology Department, Neuroimmunology Team Shanghai Jiaotong University School of Medicine Ruijin Hospital Neurology Department is a national clinical clinic of the Ministry of Health Key specialties and national key (cultivation) disciplines of the Ministry of Education
.

There are six subspecialties of Parkinson's disease and movement disorders, Alzheimer's disease and cognitive disorders, neuroimmune diseases and difficult diseases, cerebrovascular diseases, epilepsy, and sleep disorders
.

The discipline has won more than 30 first, second and third prizes of the National, Ministry of Education, Ministry of Health, Chinese Medicine, Shanghai and Shanghai Medical Awards
.

He has presided over more than 50 scientific research projects of the Ministry of Science and Technology of the People's Republic of China, "973", "863", "Major Projects of New Drug Creation", "Twelfth Five-Year Plan", National Natural Science Foundation of China, Ministry of Education and Shanghai
.

The Neuroimmunology and Difficulty Department of Neurology of Ruijin Hospital is mainly engaged in the diagnosis and treatment of autoimmune encephalitis, multiple sclerosis, central demyelinating disease, motor neuron disease and other difficult and rare diseases in neurology
.

References: [i] Hauser SL etal.
N Engl J Med.
2020;383(6):546-557.
[ii] Hauser S, Bar-Or A, Cohen J, et al.
Ofatumumab versus teriflunomide in relapsing multiplesclerosis: Analysis of no evidence of disease activity (NEDA-3) from ASCLEPIOSI and II trials.
Eur J Neurol.
2020;27(1):261–263.