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*Only for medical professionals to read and
follow the Rheumatism Youth Committee to see ACR and grasp the latest developments!
recurrence.
Figure 1.
Schematic diagram of pathological changes and microbial dysregulation of nasal epithelial cells
of rituximab.
MAINRITSAN1 demonstrated that rituximab was significantly superior to azathioprine in preventing AAV recurrence, and there was no difference in the incidence of serious adverse reactions.
MAINRITSAN2 demonstrated that relapse rates were not significantly higher in subjects who took rituximab doses individualized based on B cell count and ANCA titers; MAINRITSAN3 confirmed that the AAV recurrence rate of participants who received rituximab for 28 months followed by placebo was only 4%, and there was no difference
in adverse reaction rates.
At the same time, studies have shown that in the long-term use of rituximab, the predictors of AAV recurrence include eye, ear, and laryngeal involvement, and the protective factor for recurrence is MPO-ANCA negative
.
The MAINRITSAN series appears to have pushed rituximab to a high level of maintenance therapy, however extending the duration of rituximab from a fixed dose of 18 months to 36 months does not reduce the risk of recurrence of AAV, and the risk of recurrence after 18 months of individualized rituximab is much higher than in participants who continue to use it.
It may be preferable to extend the course to 36 months for patients who benefit from an 18-month course rather than to 36 months for all patients, suggesting that the safety and associated complications of long-term use are subject to further trials
.
of Afacopan in AAV patients The morbidity and mortality of AAV patients are closely related to renal prognosis, with studies showing that the proportion of AAV patients who progress to end-stage renal disease within 5 years reaches 15% to 38%, and once patients require dialysis, 29% to 72% Can die or be dialyzed
for a long time.
In a randomized, double-blind, double-mimic, controlled phase 3 ADVOCATE trial of 330 patients with AAV, 81% of participants enrolled with renal involvement, and the oral selective C5a receptor antagonist Avacopan showed better sustained remission at week 52 compared with prednisone tapering, i.
e.
, Avacopan helped improve renal function and may delay dialysis initiation:
Avacopan treatment is earlier than glucocorticoids to reduce proteinuria;
At the same time, avacopan significantly increased eGFR and reduced hormone use compared with glucocorticoid therapy;
Avacopan had fewer adverse events, serious adverse events, and fewer
infections than the prednisone group.
Dynamic changes in the nasal microbiome associated with disease activity in patients with granulomatosis with polyangiitis[J].
Arthritis & Rheumatology, 2021, 73(9): 1703-1712.
[3]Abreu N A, Nagalingam N A, Song Y, et al.
Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis[J].
Science translational medicine, 2012, 4(151): 151ra124-151ra124.
[4]Jaiswal S, Fontanillas P, Flannick J, et al.
Age-related clonal hematopoiesis associated with adverse outcomes[J].
New England Journal of Medicine, 2014, 371(26): 2488-2498.
[5]Jaiswal S, Natarajan P, Silver A J, et al.
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease[J].
New England Journal of Medicine, 2017, 377(2): 111-121.
follow the Rheumatism Youth Committee to see ACR and grasp the latest developments!
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can involve small blood vessels throughout the body and present as positive ANCA in serum, including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and drug-induced AAV
.
What are the new insights about AAV in recent years? The 2022 American College of Rheumatology (ACR) Annual Meeting specially opened a theme, invited 6 speakers to bring new progress in the diagnosis and treatment of AAV, and the "Medical Rheumatology and Immunology Channel" specially invited Professor Geng Yan of Peking University First Hospital to interpret
this topic.
Relapse of GPA is common and unpredictable, and respiratory involvement is common
in these patients.
The respiratory epithelial barrier is an important line of defense for the immune system and is essential for maintaining immune homeostasis, and studies have found changes in the nasal transcriptome in GPA patients [1].
Studies have also found that Corynebacterium tuberculostearicum in the nasal cavity before recurrence in GPA patients is more abundant than other bacteria, which can increase before systemic recurrence of GPA, and animal experiments have shown that this Mycobacterium tuberculosis can induce sinus lesions in mice [2-3].
recurrence.
Figure 1.
Schematic diagram of pathological changes and microbial dysregulation of nasal epithelial cells
C5a is a protein fragment released from C5 complement that plays an important role in many inflammatory conditions, attracting and activating more neutrophils, thereby inducing endothelial damage and ultimately vasculitis
.
Vilobelimab/IFX-1 is a monoclonal antibody against human complement factor C5a, which can form a high-affinity conjugate with the proven epitope, thereby blocking the biological effect of C5a in human blood to treat AAV
.
Verollimab has been shown to be effective in reducing cumulative glucocorticoid use, with excellent
response to treatment for more than 4 weeks.
At the same time, the virollimab group had significantly lower hormone-related toxicity and the lowest
number of treatment-related adverse reactions compared with other groups.
In addition, virolimab in combination with rituximab or cyclophosphamide in the treatment of GPA has the potential to induce remission and significantly reduce the dose of hormones and associated toxicity, demonstrating the safety and potential efficacy
of this novel drug for the treatment of vasculitis.
Figure 2.
Verololimab versus clinical response rates in other treatment groups
of rituximab.
MAINRITSAN1 demonstrated that rituximab was significantly superior to azathioprine in preventing AAV recurrence, and there was no difference in the incidence of serious adverse reactions.
MAINRITSAN2 demonstrated that relapse rates were not significantly higher in subjects who took rituximab doses individualized based on B cell count and ANCA titers; MAINRITSAN3 confirmed that the AAV recurrence rate of participants who received rituximab for 28 months followed by placebo was only 4%, and there was no difference
in adverse reaction rates.
At the same time, studies have shown that in the long-term use of rituximab, the predictors of AAV recurrence include eye, ear, and laryngeal involvement, and the protective factor for recurrence is MPO-ANCA negative
.
The MAINRITSAN series appears to have pushed rituximab to a high level of maintenance therapy, however extending the duration of rituximab from a fixed dose of 18 months to 36 months does not reduce the risk of recurrence of AAV, and the risk of recurrence after 18 months of individualized rituximab is much higher than in participants who continue to use it.
It may be preferable to extend the course to 36 months for patients who benefit from an 18-month course rather than to 36 months for all patients, suggesting that the safety and associated complications of long-term use are subject to further trials
.
Figure 3.
MAINRITSAN test
of Afacopan in AAV patients The morbidity and mortality of AAV patients are closely related to renal prognosis, with studies showing that the proportion of AAV patients who progress to end-stage renal disease within 5 years reaches 15% to 38%, and once patients require dialysis, 29% to 72% Can die or be dialyzed
for a long time.
In a randomized, double-blind, double-mimic, controlled phase 3 ADVOCATE trial of 330 patients with AAV, 81% of participants enrolled with renal involvement, and the oral selective C5a receptor antagonist Avacopan showed better sustained remission at week 52 compared with prednisone tapering, i.
e.
, Avacopan helped improve renal function and may delay dialysis initiation:
Avacopan treatment is earlier than glucocorticoids to reduce proteinuria;
At the same time, avacopan significantly increased eGFR and reduced hormone use compared with glucocorticoid therapy;
Avacopan had fewer adverse events, serious adverse events, and fewer
infections than the prednisone group.
Figure 4.
Avacopan reduces protein in the urine earlier than GC
About 40 genes associated with myeloid malignancy and myelodysplastic syndrome are known, and it is thought that the prevalence of mutations in hematological precursor cells in these genes increases with age or inflammation, and is referred to as CHIP when otherwise healthy people develop these conditions [4].
Studies have shown [5] that CHIP in peripheral blood cells is associated with a nearly 1-fold increased risk of human coronary heart disease, and is also associated with accelerated atherosclerosis in mice, and does the prevalence of CHIP increase in patients with systemic vasculitis, and does inflammation lead to specific CHIP progression in patients with vasculitis?
It was observed that although the incidence of CHIP in different vasculitis patients is different, the prevalence of CHIP in patients with systemic vasculitis is increased, and the relationship between age and CHIP is more closely related than inflammation, more than 50% of GCA patients have CHIP, and somatic mutations are prevalent in the blood, especially in elderly patients with systemic inflammation, perhaps indicating that the significance of CHIP in systemic vasculitis may not be important
.
Figure 5.
Proportion of somatic mutations in different systemic vasculitis
DAH is a life-threatening clinical manifestation of AAV, and studies have shown that participants with DAH differ in age, ANCA subtype and renal function, while subjects with AAV with DAH are more likely to die within 30 days and 1 year.
The effect of plasmapheresis (PLEX) on mortality was not related to the presence or absence of DAH and the severity of DAR, and there was no difference
in the effect of glucocorticoid administration on mortality between groups.
Figure 6.
Diffuse alveolar hemorrhage has a significant effect on the prognosis of AAV
Professor Geng Yan
[1] Grayson P C, Carmona‐Rivera C, Xu L, et al.
Neutrophil‐related gene expression and low‐density granulocytes associated with disease activity and response to treatment in antineutrophil cytoplasmic antibody–associated vasculitis[ J].
Arthritis & rheumatology, 2015, 67(7): 1922-1932.
Dynamic changes in the nasal microbiome associated with disease activity in patients with granulomatosis with polyangiitis[J].
Arthritis & Rheumatology, 2021, 73(9): 1703-1712.
[3]Abreu N A, Nagalingam N A, Song Y, et al.
Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis[J].
Science translational medicine, 2012, 4(151): 151ra124-151ra124.
[4]Jaiswal S, Fontanillas P, Flannick J, et al.
Age-related clonal hematopoiesis associated with adverse outcomes[J].
New England Journal of Medicine, 2014, 371(26): 2488-2498.
[5]Jaiswal S, Natarajan P, Silver A J, et al.
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease[J].
New England Journal of Medicine, 2017, 377(2): 111-121.
