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*Only for medical professionals to read reference biological preparations, a hundred flowers bloom! On August 30, 2021, at the 2021 Asia-Pacific Rheumatism Alliance (APLAR) Annual Meeting held in Kyoto, Japan, Professor Philip Mease from the Institute of Rheumatology at the Swedish Medical Center and Professor Philip Mease from the University of Washington School of Medicine shared a presentation on psoriatic arthritis ( PsA) The latest progress of treatment, let's learn and understand together! Figure 1 Professor Philip Mease's speech topic PsA is an inflammatory disease characterized by arthritis, enthesitis, dactylitis, spondylitis and psoriasis, which often leads to severe dysfunction, decreased quality of life and premature Death
.
Before the introduction of targeted biologics such as tumor necrosis factor (TNF) inhibitors, our ability to control PsA disease activity was limited, and most patients who took traditional oral drugs such as methotrexate and sulfasalazine achieved only mild effects [1]
.
The introduction of biological agents has greatly changed the appearance of PsA patients and demonstrated the ability to inhibit progressive joint structural damage
.
Into the pathophysiology of PsA and decrypt the key to PsA treatment Professor Philip Mease shared that for PsA, its pathophysiological mechanism is the key to decoding PsA treatment
.
Figure 2 Pathophysiology of PsA The pathogenesis of psoriasis is complex and has not been fully elucidated
.
Excessive activation of the adaptive immune system is considered to be the core of the pathogenesis of psoriasis [2]
.
In the initial stage of psoriasis, a variety of cells secrete various cytokines.
These cytokines cause downstream keratinocytes to proliferate, increase the expression of angiogenic mediators and endothelial adhesion molecules, and allow immune cells to infiltrate the diseased skin.
Through JAK, IL-17, cAMP/PKA, MAPK, NFκB and other signaling pathways produce various symptoms of psoriasis [3]
.
In recent years, biological agents and small molecules that target these pathways and cells have been continuously developed, and various drug treatments related to PsA are also being tested in full swing
.
Professor Philip Mease concluded that there have been many head-to-head trials on treatment, including traditional or conventional disease-improving anti-rheumatic drugs (DMARDs), biological agents such as TNFi, IL-17 inhibitors (IL-17i), and IL- 12/23 inhibitors (IL-12/23i), T cell regulators and new targeted synthetic DMARDs include phosphodiesterase 4 inhibitors and JAK inhibitors [1]
.
Figure 3 The current drug trials for the treatment of PsA are TNFi combined or monotherapy better? At the end of the last century, studies have found that high concentrations of TNF can be found in patients' joint fluid, synovium and psoriasis lesions, so a series of TNFi have been developed accordingly
.
Etanercept (ETN) is a soluble TNF receptor antagonist that binds TNF with high affinity to prevent interaction with receptors on the cell surface and initiate intracellular signal transduction, which can significantly reduce the symptoms of arthritis.
However, whether combined therapy is required when ETN is used has always been a mystery [4]
.
Therefore, Professor Philip Mease shared a double-blind phase III randomized controlled trial that he led to explore the efficacy of ETN and MTX monotherapy or combination therapy.
851 patients who had not received drug treatment were randomly divided into ETN+MTX group (n= 283), the ETN group (n=284) and the MTX group (n=284) were observed for a period of 48 weeks.
The results showed that the combined treatment of MTX and ETN was not significantly different from the treatment of ETN alone
.
Figure 4 A head-to-head study exploring two RCT biologics for ETN and MTX monotherapy or combination therapy.
Anti-(ADA) is a kind of TNFi, and the choice of these two drugs has been very tangled
.
Professor Philip Mease shared a head-to-head randomized, open-label, blinded trial on the efficacy and safety of IXE and ADA in PsA patients
.
The results of the study showed that the proportion of patients who received IXE (36%) that achieved both ACR 50 and psoriasis area and severity index (PASI 100) was significantly higher (p=0.
036) than ADA (28%)
.
Figure 5 Test results of the efficacy and safety of IXE and ADA in PsA patients.
In the era of biologics, the pathogenesis of PsA is complex, involving innate and acquired immune responses.
For this reason, many of its pathogenesis are targeted.
Targets have been discovered to a certain extent.
In this era of biological agents, many biological agents are under development and clinical trials
.
Skukuzumab is a fully human monoclonal antibody that selectively binds IL-17A.
Studies have shown that compared with the placebo group, it greatly improves arthritis, enthesitis, dactylitis, skin and The clinical response to nail disease, the radiological progression of structural joint damage is significantly reduced
.
A real-world study showed that Skuchiyuumab improved the clinical symptoms and radiological response of PsA patients [5]
.
Usinuzumab (UST) is a fully human monoclonal antibody against IL-12/23.
Two recent phase III trials have evaluated the efficacy and safety of UST, and the results show that UST is useful in the treatment of dactylitis.
And the effectiveness of enthesitis [6]
.
Bimegizumab (BMK) is a humanized monoclonal antibody that selectively binds to and neutralizes IL-17A and IL-17F
.
A randomized, double-blind, placebo-controlled Phase IIb study showed that compared with placebo, BMK is associated with a significant improvement in joint involvement and has acceptable safety [7]
.
Summary: We have entered the era of biological agents.
TNFi has always shown its unique advantages in the treatment of PsA.
Various biological agents and oral small molecules that are not inferior to TNFi are also being continuously developed and tested
.
With the continuous exploration of targeted drugs and disease pathogenesis, more reasonable and effective treatment plans for PsA patients need to be explored and created
.
Experts comment that PsA is an inflammatory joint disease related to psoriasis.
Before the introduction of biologics and small molecule targeted drugs to treat PsA, the choice of drugs is extremely limited, which seriously affects the patient's physical function and quality of life
.
With the in-depth exploration of the pathogenesis of PsA, new therapeutic targets continue to emerge, multiple clinical trials of drugs for the treatment of PsA are underway, and the relevant research results will also update our treatment concepts and management strategies
.
Currently approved drugs for the treatment of PsA or promising treatments include traditional DMARDs, biological agents such as TNFi, IL-17 inhibitors, IL-12/23 inhibitors, T cell regulators, and targeted synthetic DMARDs, such as JAK inhibitors And phosphodiesterase 4 inhibitor
.
How to individually select treatment drugs and medication plans according to the patient's specific disease so that patients can quickly achieve disease remission and long-term benefits, the answer to this question still needs more evidence-based medical evidence
.
Expert profile Li Yisha, Chief Physician, Doctor of Medicine, Master Supervisor, Chief Physician, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Deputy Director, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University Member of the Rheumatology-related Pulmonary Vascular/Interstitial Disease (Science Group) of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association, deputy chairman of the Rheumatology and Immunology Professional Committee of the Hunan Medical Association, presided over 1 National Natural Science Foundation project and 3 provincial-level projects.
1 school-level topic, 1 college-level topic, published multiple SCI papers and statistical source journal papers reference: [1]Mease PJ.
Biologic Therapy for Psoriatic Arthritis.
Rheum Dis Clin North Am.
2015;41(4): 723-738.
doi:10.
1016/j.
rdc.
2015.
07.
010[2]Nestle FO,Kaplan DH,Barker J.
Mechanisms of disease:psoriasis.
N Engl J Med.
2009;361(5):496-509.
doi :10.
1109/APCCAS.
2002.
1114931[3]Alwan W,Nestle FO.
Pathogenesis and treatment of psoriasis:exploiting pathophysiological pathways for precision medicine.
Clin Exp Rheumatol.
2015;33(5)(suppl 93):S2-S6.
[4] Mease PJ,Kivitz AJ,Burch FX,et al.
Etanercept treatment of psoriatic arthritis:safety,efficacy,and effect on disease progression.
Arthritis Rheum.
2004;50(7):2264-2272.
doi:10.
1002/art.
20335[ 5] Chimenti MS, Fonti GL, Conigliaro P, et al.
One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study.
Expert Opin Biol Ther.
2020;20(7):813-821.
doi:10.
1080/14712598.
2020.
1761957[ 6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177 /2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled,dose-ranging phase 2b trial.
Lancet .
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7doi:10.
1080/14712598.
2020.
1761957[6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177/2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7doi:10.
1080/14712598.
2020.
1761957[6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177/2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7double-blind, placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7double-blind, placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7
.
Before the introduction of targeted biologics such as tumor necrosis factor (TNF) inhibitors, our ability to control PsA disease activity was limited, and most patients who took traditional oral drugs such as methotrexate and sulfasalazine achieved only mild effects [1]
.
The introduction of biological agents has greatly changed the appearance of PsA patients and demonstrated the ability to inhibit progressive joint structural damage
.
Into the pathophysiology of PsA and decrypt the key to PsA treatment Professor Philip Mease shared that for PsA, its pathophysiological mechanism is the key to decoding PsA treatment
.
Figure 2 Pathophysiology of PsA The pathogenesis of psoriasis is complex and has not been fully elucidated
.
Excessive activation of the adaptive immune system is considered to be the core of the pathogenesis of psoriasis [2]
.
In the initial stage of psoriasis, a variety of cells secrete various cytokines.
These cytokines cause downstream keratinocytes to proliferate, increase the expression of angiogenic mediators and endothelial adhesion molecules, and allow immune cells to infiltrate the diseased skin.
Through JAK, IL-17, cAMP/PKA, MAPK, NFκB and other signaling pathways produce various symptoms of psoriasis [3]
.
In recent years, biological agents and small molecules that target these pathways and cells have been continuously developed, and various drug treatments related to PsA are also being tested in full swing
.
Professor Philip Mease concluded that there have been many head-to-head trials on treatment, including traditional or conventional disease-improving anti-rheumatic drugs (DMARDs), biological agents such as TNFi, IL-17 inhibitors (IL-17i), and IL- 12/23 inhibitors (IL-12/23i), T cell regulators and new targeted synthetic DMARDs include phosphodiesterase 4 inhibitors and JAK inhibitors [1]
.
Figure 3 The current drug trials for the treatment of PsA are TNFi combined or monotherapy better? At the end of the last century, studies have found that high concentrations of TNF can be found in patients' joint fluid, synovium and psoriasis lesions, so a series of TNFi have been developed accordingly
.
Etanercept (ETN) is a soluble TNF receptor antagonist that binds TNF with high affinity to prevent interaction with receptors on the cell surface and initiate intracellular signal transduction, which can significantly reduce the symptoms of arthritis.
However, whether combined therapy is required when ETN is used has always been a mystery [4]
.
Therefore, Professor Philip Mease shared a double-blind phase III randomized controlled trial that he led to explore the efficacy of ETN and MTX monotherapy or combination therapy.
851 patients who had not received drug treatment were randomly divided into ETN+MTX group (n= 283), the ETN group (n=284) and the MTX group (n=284) were observed for a period of 48 weeks.
The results showed that the combined treatment of MTX and ETN was not significantly different from the treatment of ETN alone
.
Figure 4 A head-to-head study exploring two RCT biologics for ETN and MTX monotherapy or combination therapy.
Anti-(ADA) is a kind of TNFi, and the choice of these two drugs has been very tangled
.
Professor Philip Mease shared a head-to-head randomized, open-label, blinded trial on the efficacy and safety of IXE and ADA in PsA patients
.
The results of the study showed that the proportion of patients who received IXE (36%) that achieved both ACR 50 and psoriasis area and severity index (PASI 100) was significantly higher (p=0.
036) than ADA (28%)
.
Figure 5 Test results of the efficacy and safety of IXE and ADA in PsA patients.
In the era of biologics, the pathogenesis of PsA is complex, involving innate and acquired immune responses.
For this reason, many of its pathogenesis are targeted.
Targets have been discovered to a certain extent.
In this era of biological agents, many biological agents are under development and clinical trials
.
Skukuzumab is a fully human monoclonal antibody that selectively binds IL-17A.
Studies have shown that compared with the placebo group, it greatly improves arthritis, enthesitis, dactylitis, skin and The clinical response to nail disease, the radiological progression of structural joint damage is significantly reduced
.
A real-world study showed that Skuchiyuumab improved the clinical symptoms and radiological response of PsA patients [5]
.
Usinuzumab (UST) is a fully human monoclonal antibody against IL-12/23.
Two recent phase III trials have evaluated the efficacy and safety of UST, and the results show that UST is useful in the treatment of dactylitis.
And the effectiveness of enthesitis [6]
.
Bimegizumab (BMK) is a humanized monoclonal antibody that selectively binds to and neutralizes IL-17A and IL-17F
.
A randomized, double-blind, placebo-controlled Phase IIb study showed that compared with placebo, BMK is associated with a significant improvement in joint involvement and has acceptable safety [7]
.
Summary: We have entered the era of biological agents.
TNFi has always shown its unique advantages in the treatment of PsA.
Various biological agents and oral small molecules that are not inferior to TNFi are also being continuously developed and tested
.
With the continuous exploration of targeted drugs and disease pathogenesis, more reasonable and effective treatment plans for PsA patients need to be explored and created
.
Experts comment that PsA is an inflammatory joint disease related to psoriasis.
Before the introduction of biologics and small molecule targeted drugs to treat PsA, the choice of drugs is extremely limited, which seriously affects the patient's physical function and quality of life
.
With the in-depth exploration of the pathogenesis of PsA, new therapeutic targets continue to emerge, multiple clinical trials of drugs for the treatment of PsA are underway, and the relevant research results will also update our treatment concepts and management strategies
.
Currently approved drugs for the treatment of PsA or promising treatments include traditional DMARDs, biological agents such as TNFi, IL-17 inhibitors, IL-12/23 inhibitors, T cell regulators, and targeted synthetic DMARDs, such as JAK inhibitors And phosphodiesterase 4 inhibitor
.
How to individually select treatment drugs and medication plans according to the patient's specific disease so that patients can quickly achieve disease remission and long-term benefits, the answer to this question still needs more evidence-based medical evidence
.
Expert profile Li Yisha, Chief Physician, Doctor of Medicine, Master Supervisor, Chief Physician, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Deputy Director, Department of Rheumatology and Immunology, Xiangya Hospital, Central South University Member of the Rheumatology-related Pulmonary Vascular/Interstitial Disease (Science Group) of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association, deputy chairman of the Rheumatology and Immunology Professional Committee of the Hunan Medical Association, presided over 1 National Natural Science Foundation project and 3 provincial-level projects.
1 school-level topic, 1 college-level topic, published multiple SCI papers and statistical source journal papers reference: [1]Mease PJ.
Biologic Therapy for Psoriatic Arthritis.
Rheum Dis Clin North Am.
2015;41(4): 723-738.
doi:10.
1016/j.
rdc.
2015.
07.
010[2]Nestle FO,Kaplan DH,Barker J.
Mechanisms of disease:psoriasis.
N Engl J Med.
2009;361(5):496-509.
doi :10.
1109/APCCAS.
2002.
1114931[3]Alwan W,Nestle FO.
Pathogenesis and treatment of psoriasis:exploiting pathophysiological pathways for precision medicine.
Clin Exp Rheumatol.
2015;33(5)(suppl 93):S2-S6.
[4] Mease PJ,Kivitz AJ,Burch FX,et al.
Etanercept treatment of psoriatic arthritis:safety,efficacy,and effect on disease progression.
Arthritis Rheum.
2004;50(7):2264-2272.
doi:10.
1002/art.
20335[ 5] Chimenti MS, Fonti GL, Conigliaro P, et al.
One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study.
Expert Opin Biol Ther.
2020;20(7):813-821.
doi:10.
1080/14712598.
2020.
1761957[ 6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177 /2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled,dose-ranging phase 2b trial.
Lancet .
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7doi:10.
1080/14712598.
2020.
1761957[6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177/2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7doi:10.
1080/14712598.
2020.
1761957[6]Dobbin-Sears I, Roberts J, O'Rielly DD, Rahman P.
Ustekinumab in psoriatic arthritis and related phenotypes.
Ther Adv Chronic Dis.
2018;9(10):191-198.
Published 2018 Jun 13.
doi:10.
1177/2040622318781760[7]Ritchlin CT,Kavanaugh A,Merola JF,et al.
Bimekizumab in patients with active psoriatic arthritis:results from a 48-week,randomised,double-blind,placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7double-blind, placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7double-blind, placebo-controlled, dose-ranging phase 2b trial.
Lancet.
2020;395(10222):427-440.
doi:10.
1016/S0140-6736(19)33161-7
