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*For medical professionals only, the 38th ECTRIMS Conference ended successfully, wonderful content, not to be missed!
for the treatment of RMS and PPMS.
Currently, Ocrelizumab has been approved in more than 100 countries and more than 250,000 patients have been treated
.
org.
cn
Among the central nervous system demyelinating diseases, neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) are of great concern, both of which are recurrent and the patient's quality of life is seriously affected as the course of the disease progresses and the degree of disability gradually increases
.
The 38th European Commission for Multiple Sclerosis Research and Treatment Conference (ECTRIMS 2022) was successfully held at the end of October this year, the conference is rich in content and full of dry goods, this article extracts the latest and hottest content about NMOSD and MS in clinical diagnosis and treatment, clinical research methods, expert consensus, etc.
NMOSD is a rare, recurrent central nervous system autoimmune disease, clinically manifested as severe optic neuritis and/or longitudinal extension of transverse myelitis, clinical symptoms are extensive, including blindness, movement disorders, pain, fatigue and urinary incontinence, most patients can be disabled due to repeated attacks of the disease, 50% of patients need a wheelchair within 5 years, 62% of patients are blind
.
The meeting launched an international expert consensus statement on the management of AQP4-IgG seropositive NMOSD based on evidence-based evidence, in which Satralizumab, a subcutaneously injected humanized IgG2 monoclonal antibody capable of specifically binding to IL-6R, blocking IL-6 signal transduction, inhibiting AQP4-IgG production and alleviating IL-6-associated neuroinflammation
。 Compared with traditional IgG1 antibodies, satrolizumab adopts recirculation antibody technology, which can bind to antigens multiple times, prolong the plasma half-life of the drug, reduce the dose of administration, and improve safety
.
Fig.
1 Mechanism of action of satrolizumab
The expert consensus adopts the internationally accepted Delphi procedure, and after full discussion and two rounds of voting on the draft consensus by 24 experts, the consensus reached consensus on 25 items, which helped to make clinical decisions, improve patient outcomes, and lay the foundation for the
development of standardized practice guidelines.
Table 1 Statement of international expert consensus on the management of AQP4-IgG seropositive NMOSD based on evidence-based evidence
(Swipe down to view table)Another parallel finding was shared at this consensus NMOSD treatment recommendation, which focuses on three drugs, Satralizumab, Eculizumab, and Inebilizumab, and that a variety of therapeutic drug options often means that the process of treatment decisions is becoming more complex.
By reviewing clinical records and patient interviews, the potential reasons for
initiating treatment and selecting therapeutic drugs in patients with NMOSD in the process of clinical practice were analyzed.
The study summarizes the following four aspects in the whole process of NMOSD disease management
.
About a quarter of people with NMOSD experience misdiagnosis
The study provided clinical records of 1185 patients and completed interviews
with 33 patients.
Of all patients last diagnosed with NMOSD, approximately 25% (228/910) were initially misdiagnosed with MS, essential myelitis, optic neuritis, and stroke, and 24% (8/33) experienced misdiagnosis
.
Patients with misdiagnosis typically experienced longer time to start maintenance therapy than those diagnosed at the outset (21.
2 versus 9.
9 months; p<0.
05), they also experienced more recurrences (3.
3 vs 2.
8, p<0.
05) and were more likely to have severe relapses (23% vs 10%)
.
Hormonal or immunosuppressive agents remain first-line maintenance regimens
For patients with NMOSD, oral corticosteroids or immunosuppressants (ISTs) (e.
g.
, azathioprine, mycophenolate mofetil, cyclophosphamide, mitoxantrone) are typical first-line maintenance therapy
.
Only neurologists in the United States will consider the use of monoclonal antibodies
initially.
First-line therapy regimens usually depend on the severity of the onset, with glucocorticoids/ISTs used at a higher rate than monoclonal antibodies in patients with mild episodes (52 versus 25 percent
).
76% (25/33) of the patients surveyed did not know that a drug switch could be made, and many patients did not know why they changed their medication
.
Nearly half of the patients did not receive maintenance therapy within 2 months
For a variety of reasons, 47% of patients with NMOSD did not initiate maintenance therapy within 2 months of initial consultation, and those who started treatment within 2 months were more likely to experience a severe initial episode (13% versus 5%)
.
Figure 2 Reasons for treatment delay
Poor efficacy is the main reason for drug switching during NMOSD treatment
In clinical practice, the efficacy of a drug is mainly evaluated by the presence or absence of recurrence and the severity of the disease, and poor efficacy often leaves clinicians with the problem
of drug switching choices.
Fig.
3 Common drug switching causes during NMOSD treatment
MS is a chronic, recurrent inflammatory, demyelinating central nervous system degenerative disease
.
There are about 2.
8 million cases of MS patients in the world, more common in young adults, more common in women, the incidence of MS in China is about 0.
235/100,000 per year, and there are about 3-50,000 patients
in China.
MS causes neuroinflammation and tissue damage due to autoimmune system disorders, resulting in dysfunction of the brain, optic nerve and spinal cord, and clinical manifestations of muscle weakness, vision loss and autonomic dysfunction, etc.
, and patients can accumulate disability
due to repeated attacks.
In the clinical management of MS, attention should be paid to confirmed disability progressions (CDP), defined as the progress of disability from baseline, and the assessment method is based on the Extended Disability Status Scale (EDSS), that is, the baseline EDSS score ≤ 5.
5 points, an increase of 1.
0 points, or a baseline EDSS score >5.
5 points, an increase of 0.
5 points is called CDP, in addition to EDSS, timed 25-foot walking test (T25FW) The 9-well test (9HPT) can also be used to assess
the progression of MS disability.
The usual time to confirm disability is 12 weeks, with studies suggesting 24 or 48 weeks
.
In MS-related phase III randomized clinical trials, the most widely used endpoint indicator is the time to the first CDP event, but this indicator is also recognized to have many limitations
.
At this conference, experts proposed that the above indicators cannot fully reflect the CDP events independent of the analysis set, including the end of the trial, during the drug administration, and repeated occurrences, which may lead to the inability to accurately evaluate the overall efficacy of a disease-modifying therapy (DMT) drug in the clinical trial process, and they further proposed that repeated disability progression event analysis in clinical trials can more comprehensively evaluate the efficacy of DMT drugs and more accurately describe the long-term disability progression of patients with progressive MS
。
In order to more fully evaluate the long-term efficacy and therapeutic potential of early use of Ocrelizumab, experts at the conference based on data from three studies and their open-label extension trials [in 2017, the first data were released in three phase III clinical trials of Ocrelizumab for MS, namely OPERA I and II studies on recurrent multiple sclerosis (RMS) and ORATORIO studies on primary progressive multiple sclerosis (PPMS)] Repeated CDP event analysis
was performed.
for the treatment of RMS and PPMS.
Currently, Ocrelizumab has been approved in more than 100 countries and more than 250,000 patients have been treated
.
Repeat CDP event analysis in patients with PPMS
In the 8-year ORATORIO study and its open-label extension trial, it was found that patients who started Ocrelizumab early had significantly lower rates of repeated 48-week CDP-EDSS, CDP-9HPT, CDP-T25FW, and composite CDP (cCDP) (23%, 35%, 24%, and 26%, respectively
).
There was no significant difference in the rate of annualized repetitive disability progression between continuous use of Ocrelizumab and the transition group, suggesting that early application of Ocrelizumab could effectively reduce the incidence
of repeated CDP events.
Fig.
4 Comparison of the incidence of 48-week CDP-EDSS and the rate of annualized repeated disability progression events between the experimental group and the control group in PPMS
Fig.
5 Comparison of the incidence of 48-week CDP-9HPT and the annualized rate of repeated disability progression events in the experimental group and the control group in PPMS
Fig.
6 Comparison of the incidence of 48-week CDP-T25FW and the annualized rate of repeated disability progression in PPMS between the experimental group and the control group
Fig.
7 Comparison of the incidence of 48-week cCDP and the annualized rate of repeated disability progression events between the experimental group and the control group in PPMS
Analysis of repeat CDP events in patients with RMS
In the OPERA I/II study and its open-label extension trial, it was also found that the incidence of repeated CDP-EDSS at 48 weeks was significantly reduced (27%)
in patients who received Ocrelizumab early.
After conversion from interferon β-1a to Ocrelizumab, the rate of annualized repetitive disability progression events was similar
between continuous use of Ocrelizumab and the transition groups.
One-fifth of patients experienced an event of progression greater than 348 weeks in the continuous use group, while this time was shortened to 252 weeks in the transition group, suggesting that Ocrelizumab secured approximately 96 weeks of delayed disability events for RMS patients
.
Fig.
8 Comparison of the incidence of 48-week CDP-EDSS and the annualized rate of repeated disability progression between the experimental group and the control group in RRMS
Fig.
9 Disease activity between the experimental group and the control group in RRMS
Floodlight, a digital disease management tool, is used for symptom monitoring in MS patients
Since the onset of the pandemic in 2019, it has become more difficult for people with a chronic condition such as MS to get to the hospital, which has also made it impossible for doctors to regularly assess
the patient's condition.
Floodlight is a smartphone sensor-based monitoring tool that enables active and passive monitoring of patients at home, and these test data will be uploaded to the terminal for analysis, helping to fully understand the changes in the course of MS patients, filling a critical gap
in MS research and clinical care 。 The CONSONANCE study, a phase IIIb open-label study by Ocrelizumab in patients with progressive MS, requires MS patients to undergo daily testing and passive monitoring of hand function, balance function, and gait function through Floodlight, and cognitive function assessment at least once a week
.
At this ECTRIMS conference, experts described the long-term compliance performance pattern of MS patients using Floodlight in the CONSONANCE study, and finally a total of 327 patients who used the product for at least 2 years were included in the analysis, and finally divided into 5 groups, namely high adherence group, low compliance group, slow decline in participation group, rapid decline in participation group and unable to walk test group:
Figure 10 People with different engagement characteristics using Floodlight
MS patients with different conditions and different levels of disability progression have different Floodlight usage behavior patterns, which are usually formed early in use and can help predict future adherence to the product
.
Adherence is generally higher in patients with more severe disability, and the study will follow patients further to determine the reasons
behind this pattern of use.
Exploring these factors can more accurately interpret the data uploaded by Floodlight and fully understand the real condition of patients with progressive MS, so as to optimize the monitoring mode and data collection methods in future trial designs and improve the application of
Floodlight in MS-related clinical trials.
small
knot
NMOSD is often misdiagnosed as MS, which leads to delays in initiation of treatment, so the diagnosis of NMOSD should be further improved
.
In countries where monoclonal antibody use is limited, corticosteroids/ISTs remain first-line maintenance regimens
.
Treatment decisions often depend on the recurrence and severity of the disease, and poor response to a drug often leads to drug switching, which warrants further research to suggest revisions to treatment decisions for NMOSD
.
In MS-related clinical studies, repeated CDP event analysis can help researchers assess the efficacy of drugs more comprehensively, and better describe the long-term trajectory of disability progression and treatment response response
.
Smartphone-based remote digital monitoring Floodlight can be used to assess activity and functional performance in MS patients, and differences in patient adherence may suggest the reasons
behind more behavioral patterns.
In conclusion, early and sustained use of Ocrelizumab in patients with RMS and PPMS was effective in delaying disability progression
.
*This article is for scientific information provided only to healthcare professionals and does not represent the views of the platform
Submission/Reprint/Business Cooperation: yxjsjbx@yxj.org.
cn
