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*For medical professionals only, hand in hand
to move forward and grow
together with the Chinese immunology field.
Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases involving improper or excessive immune responses, including rheumatoid arthritis (RA), systemic lupus erythematosus, psoriasis and many other diseases
。 Over the past two decades, the therapeutic development of IMIDs has evolved rapidly, from initial broad-spectrum immunomodulators to specific formulations to targeted drugs, and their development has continued to change clinical treatment strategies
.
At present, the treatment of rheumatic immunity and skin immune diseases has entered the era
of biological agents and targeted drugs.
For example, the emergence of biologically modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) has promoted the treatment strategy of RA from pain relief to standard treatment
.
A variety of biologics have also been approved for the treatment of psoriasis, systemic lupus erythematosus and other diseases, but there are still many unmet clinical needs and treatment challenges
in clinical practice.
In order to further discuss and look forward to the future development trend in the field of skin immunity and rheumatic immune diseases, Lilly Academy of Immunology held the third anniversary celebration meeting of "Focus on Immunity, Empower the Future" on November 20, 2022, and many well-known experts in the field of rheumatoid immunity and skin immunity at home and abroad gathered in the cloud.
The unmet clinical needs and challenges in the field of diseases were fully exchanged and discussed, as well as the prospects
for the development trends in this field.
This article will specifically sort out the academic reports shared by two overseas experts, Professor Paul Emery of the University of Leeds and Professor Diamant Thaci of the University of Lubeck, Germany, at the third anniversary celebration meeting of "Focus on Immunity, Empower the Future", focusing on the frontier trends and latest research progress of rheumatism and skin immune diseases for the majority of clinicians to learn and communicate
。
Professor Diamant Thaci of the University of Lubeck, Germany, gave a report entitled "Unmet Clinical Needs and Future Challenges in Immune-Mediated Skin Diseases", Professor Diamant Thaci mentioned 17 chronic non-infectious skin inflammatory diseases such as psoriasis, prurigo nodosum, vitiligo, chronic spontaneous urticaria and other 17 chronic non-infectious skin inflammatory diseases in a recent review article, the pathogenesis of these diseases is generally related to immunity and inflammation.
Prevalence is increasing, affecting approximately 15 to 20 percent of the population, and there are challenges in diagnosis, a general lack of curative therapies, often comorbidities, significant disease and economic burden, and many unmet treatment needs [1].
Some scholars have divided immune-mediated skin diseases into three categories: allergic, autoimmune and autoinflammatory diseases (see Figure 1) [2], and there have been many studies on autoinflammatory diseases in the past, but the diagnosis and accurate classification of diseases such as Behcet's disease still have many challenges
。 For example, in the field of psoriasis, the discovery of key pathways including type 1 interferon and antiviral signaling pathways, NF-κB, IL-23/IL-17, and antigen processing and presentation pathways, combined with immunological studies, has a clear explanation of the pathogenesis of psoriasis and has made significant progress in the treatment of psoriasis [3]
。
Figure 1: Classification
of immune-mediated skin diseases In the current European guidelines for the systematic treatment of psoriasis vulgaris (EuroGuiDerm version), eight different biologics have been recommended for first-line treatment of patients [4] , but how to choose biologics to enable patients to achieve PASI (psoriasis area and severity index) efficacy of 100 is still up in the air
.
The academic community often uses "Number Needed to Treat" (NNT) to evaluate the overall efficacy of drugs on patients, and the NNT of biological agents is generally better than other drugs [5], but it is still difficult to predict the efficacy of individual patients and determine the best biological agents
.
Figure 2.
NNT comparison
of different psoriasis biologics and other partial therapeutic drugs The goal of further developing innovative therapeutic drugs is not only to enable more patients to achieve PASI 100 response, but also to help patients achieve disease remission, that is, to prevent recurrence after stopping treatment
。 Current research suggests that tissue intrinsic memory T cells (T RM Cells) may be the key to inflammation-mediated recurrence of skin diseases, and even after long-term systemic treatment, site-specific "disease memory" established by T RMcells may reactivate inflammation and lead to psoriasis recurrence [6], regulatory T cells (TRegCells) can also infiltrate into psoriasis plaques [7].
It is worth noting that the inflammatory factors such as IL-17 targeted in the treatment of psoriasis may also be involved in the disease process such as cancer and infection, so the impact of targeting these sites on treatment safety, potential therapeutic benefits, and traditional considerations such as disease activity, patient needs, doctors' experience, etc.
are all issues that need to be considered when selecting therapeutic drugs, and appropriate biomarkers are found to guide treatment.
It is a clinical need that is not met today and the direction of development in the future (see Figure 3).
In addition, comorbidities such as metabolic syndrome, (cardio)vascular and mental health disorders are challenges in the management of almost all chronic inflammatory skin diseases
.
Figure 3.
Considerations
for treatment decisions, Professor Diamant Thaci concluded, believing that in the next few years, the diagnosis and treatment of chronic inflammatory skin diseases will change significantly, resulting in further improvement in the quality of life of patients.
And this requires continuous progress
in precision medicine.
Professor Paul Emery's presentation topic was "Unmet Treatment Needs for RA", and Professor Paul Emery summarized the four major unmet treatment needs including: 1) better patient-reported outcomes (PROs), less pain and disability, including quality of life, 2) higher treatment response rate 3) maintenance of remission after slow tapering of medication 4) Prevention of arthritis first in order to achieve better PROs, reduce pain and disability, it is necessary to effectively control the disease activity of RA, studies have shown that pain is the most important cognition of disease activity in RA patients, but doctors often take the number of swollen joints as an evaluation criterion [8],
And many patients with RA still have significant pain
when disease activity is low.
In this case, drugs that target multiple sites and pathways can be selected, such as JAK inhibitors, which can directly or indirectly modulate signaling pathways related to inflammation and pain (see Figure 4), thereby effectively reducing pain while alleviating joint symptoms in RA patients [9].
Figure 4.
JAK inhibitors can directly or indirectly modulate signaling pathways
related to inflammation and pain, and in terms of achieving higher therapeutic response rates, with the continuous advancement of therapeutic drugs and the strong recommendation of authoritative guidelines, all patients with treatment-naïve RA should aim to achieve therapeutic remission, and drugs with higher
success rates should be selected as much as possible 。 Professor Paul Emery believes based on personal experience that the first-line treatment rate of traditional drugs such as methotrexate (MTX) has obviously not met the demand, and most patients in the real world cannot tolerate the full dose of MTX, and unsuccessful MTX treatment may also change the course of the disease, making it difficult to respond
to subsequent treatments.
Therefore, in order to achieve remission in more patients as early as possible, it is considered to predict response before treatment, as previous studies have shown that a lower baseline number of initial CD4+ T cells in patients with early RA can predict a lower response rate at six months of treatment [10].
Professor Paul Emery believes that in terms of drug reduction, the main patients who can be considered for reduction are patients who receive treatment early in the course of the disease, achieve deep remission early and can be maintained, in addition to no joint damage, normal function and good quality of life, young patients, low baseline disease activity, no glucocorticoids, seronegative and other factors can also be considered.
The above factors can be combined to formulate a clinical practical scoring system
to guide the reduction.
In addition, tapering
may be considered in patients who achieve a "multidimensional response" (MDR) as assessed by clinical symptoms, imaging, and immunomarkers, see Figure 5 。 A study led by Professor Paul Emery's team showed that about one-third of RA patients who achieved traditional DAS28 remission achieved MDR, and these patients reported better PROs overall, suggesting that MDR can be an ideal target for standard therapy (T2T) for RA patients from a patient perspective [11].
Figure 5.
The concept
of multidimensional response (MDR) For patients treated with bDMRADs, complete discontinuation is still not a realistic goal, considering that some patients may lose response when rebounding after treatment discontinuation should be considered, and only patients who have successfully achieved dose reduction should be considered for entering the discontinuation process
。 Available evidence suggests that bDMRADs may be considered for six months of clinical remission (normal CRP, zero number of swollen joints) and treated with MTX without glucocorticoids, and should be considered for discontinuation of bDMRADs only if symptoms do not worsen three months after the last reduction and there are good prognostic factors [12].
。
The last unmet therapeutic need is the prevention of arthritis, and in the past, whether screening people with anti-citrullinated protein antibodies (ACPA) positive or focusing on patients with clinically suspected arthralgia (CSA), was not enough to identify and intervene in the risk of RA "pre-clinical", so the current RA clinical diagnosis process focuses on three issues.
Namely: 1) identification of risk groups; 2) assess the risk of progression to RA; 3) Intervene to reduce risk
.
A national, observational study conducted by Professor Paul Emery's team, based on 10 years of data from the UK Primary Care Network, showed that patients with high anti-cyclic citrullinated peptide 2 antibody (CCP2) titers and hand or foot pain symptoms had a relatively highest risk of progression to RA, while patients without these two features had a low risk of progression (negative predictive value 96%) [13], which helps optimize the clinical diagnostic process and reduce delayed diagnosis
.
Another study showed that the use of third-generation anti-CCP3 antibodies was also more effective than anti-CCP2 antibodies in predicting the risk of disease progression in people at risk of RA [14].
In addition, many local factors also affect the microbial and mucosal immune status, which in turn affects the "local immunity" of RA patients, thus becoming the cause of RA, such as the high prevalence of periodontal disease in RA patients and ACPA-positive people (see Figure 6), and there are common risk factors such as smoking between the two, so it is necessary to pay attention to the risk of RA in patients with periodontal disease.
Interventions such as the treatment of Porphyromonas gingivalis are considered to delay or even prevent the onset of RA [15].
Fig.
6.
The prevalence of
periodontitis in healthy control population, CCP-positive RA risk group and early RA patients, and from the perspective of RA disease process, for anti-CCP antibody-positive people with skeletal muscle symptoms, ultrasound showed the presence of subclinical synovitis, May be a very predictive stage
in the disease process.
To prevent future joint lesions, it may not wait for typical joint symptoms in this group of people, but try to intervene
early.
A recent analysis by Professor Paul Emery's team showed that anti-CCP3 antibody positivity helps predict the progression of anti-CCP2 antibody-positive people to subclinical synovitis, meaning that screening antibody-positive people can provide a critical time window for early intervention (see Figure 7) [16].
Figure 7.
Time window for early intervention to prevent RA patients from progressing to arthritis
References: [1]Ujiie H, Rosmarin D, Schön M P, et al.
Unmet medical needs in chronic, non-communicable inflammatory skin diseases[J].
Frontiers in Medicine, 2022: 875492.
[2]Satoh T K, Mellett M, Contassot E, et al.
Are neutrophilic dermatoses autoinflammatory disorders? [J].
British Journal of Dermatology, 2018, 178(3): 603-613.
[3]Griffiths CEM, et al.
Psoriasis.
Lancet 2021; 397:1301-15.
[4]Nast A, Smith C, Spuls P I, et al.
EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris–Part 1: treatment and monitoring recommendations[J].
Journal of the European Academy of Dermatology and Venereology, 2020, 34(11): 2461-2498.
[5]Sawyer L M, Malottki K, Sabry-Grant C, et al.
Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response[J].
PLoS One, 2019, 14(8): e0220868.
[6]Cheuk S, Wikén M, Blomqvist L, et al.
Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis[J].
The Journal of Immunology, 2014, 192(7): 3111-3120.
[7]Liu Y, Jarjour W, Olsen N, et al.
Traitor or warrior–Treg cells sneaking into the lesions of psoriatic arthritis[J].
Clinical Immunology, 2020, 215: 108425.
[8]Studenic P, Radner H, Smolen J S, et al.
Discrepancies between patients and physicians in their perceptions of rheumatoid arthritis disease activity[J].
Arthritis & Rheumatism, 2012, 64(9): 2814-2823.
[9]Simon L S, Taylor P C, Choy E H, et al.
The Jak/STAT pathway: A focus on pain in rheumatoid arthritis[C]//Seminars in Arthritis and Rheumatism.
WB Saunders, 2021, 51(1): 278-284.
[10]Ponchel F, Goëb V, Parmar R, et al.
An immunological biomarker to predict MTX response in early RA[J].
Annals of the Rheumatic Diseases, 2014, 73(11): 2047-2053.
[11]Gul H L, Eugenio G, Rabin T, et al.
Defining remission in rheumatoid arthritis: does it matter to the patient? A comparison of multi-dimensional remission criteria and patient reported outcomes[J].
Rheumatology, 2020, 59(3): 613-621.
[12]Liana Fraenkel,et al.
2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.
Arthritis Rheumatol .
2021 Jul; 73(7):1108-1123.
[13]Garcia-Montoya L, Nam J L, Duquenne L, et al.
Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study[J].
Arthritis Research & Therapy, 2022, 24: 26.
[14]Di Matteo A, Mankia K, Duquenne L, et al.
Third‐Generation Anti–Cyclic Citrullinated Peptide Antibodies Improve Prediction of Clinical Arthritis in Individuals at Risk of Rheumatoid Arthritis[J].
Arthritis & Rheumatology, 2020, 72(11): 1820-1828.
[15]Mankia K, Cheng Z, Do T, et al.
Prevalence of periodontal disease and periodontopathic bacteria in anti–cyclic citrullinated protein antibody–positive at-risk adults without arthritis[J].
JAMA Network Open, 2019, 2(6): e195394.
[16]Di Matteo A, Duquenne L, Cipolletta E, et al.
Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum[J].
Rheumatology, 2022, 61(8): 3192-3200.
This article is only for providing scientific information to healthcare professionals and does not represent the position of
the platform.
to move forward and grow
together with the Chinese immunology field.
Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases involving improper or excessive immune responses, including rheumatoid arthritis (RA), systemic lupus erythematosus, psoriasis and many other diseases
。 Over the past two decades, the therapeutic development of IMIDs has evolved rapidly, from initial broad-spectrum immunomodulators to specific formulations to targeted drugs, and their development has continued to change clinical treatment strategies
.
At present, the treatment of rheumatic immunity and skin immune diseases has entered the era
of biological agents and targeted drugs.
For example, the emergence of biologically modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) has promoted the treatment strategy of RA from pain relief to standard treatment
.
A variety of biologics have also been approved for the treatment of psoriasis, systemic lupus erythematosus and other diseases, but there are still many unmet clinical needs and treatment challenges
in clinical practice.
In order to further discuss and look forward to the future development trend in the field of skin immunity and rheumatic immune diseases, Lilly Academy of Immunology held the third anniversary celebration meeting of "Focus on Immunity, Empower the Future" on November 20, 2022, and many well-known experts in the field of rheumatoid immunity and skin immunity at home and abroad gathered in the cloud.
The unmet clinical needs and challenges in the field of diseases were fully exchanged and discussed, as well as the prospects
for the development trends in this field.
This article will specifically sort out the academic reports shared by two overseas experts, Professor Paul Emery of the University of Leeds and Professor Diamant Thaci of the University of Lubeck, Germany, at the third anniversary celebration meeting of "Focus on Immunity, Empower the Future", focusing on the frontier trends and latest research progress of rheumatism and skin immune diseases for the majority of clinicians to learn and communicate
。
Spotlight on Immune-Mediated Skin Diseases – Where Does the Future Lead?
Professor Diamant Thaci of the University of Lubeck, Germany, gave a report entitled "Unmet Clinical Needs and Future Challenges in Immune-Mediated Skin Diseases", Professor Diamant Thaci mentioned 17 chronic non-infectious skin inflammatory diseases such as psoriasis, prurigo nodosum, vitiligo, chronic spontaneous urticaria and other 17 chronic non-infectious skin inflammatory diseases in a recent review article, the pathogenesis of these diseases is generally related to immunity and inflammation.
Prevalence is increasing, affecting approximately 15 to 20 percent of the population, and there are challenges in diagnosis, a general lack of curative therapies, often comorbidities, significant disease and economic burden, and many unmet treatment needs [1].
Some scholars have divided immune-mediated skin diseases into three categories: allergic, autoimmune and autoinflammatory diseases (see Figure 1) [2], and there have been many studies on autoinflammatory diseases in the past, but the diagnosis and accurate classification of diseases such as Behcet's disease still have many challenges
。 For example, in the field of psoriasis, the discovery of key pathways including type 1 interferon and antiviral signaling pathways, NF-κB, IL-23/IL-17, and antigen processing and presentation pathways, combined with immunological studies, has a clear explanation of the pathogenesis of psoriasis and has made significant progress in the treatment of psoriasis [3]
。
Figure 1: Classification
of immune-mediated skin diseases In the current European guidelines for the systematic treatment of psoriasis vulgaris (EuroGuiDerm version), eight different biologics have been recommended for first-line treatment of patients [4] , but how to choose biologics to enable patients to achieve PASI (psoriasis area and severity index) efficacy of 100 is still up in the air
.
The academic community often uses "Number Needed to Treat" (NNT) to evaluate the overall efficacy of drugs on patients, and the NNT of biological agents is generally better than other drugs [5], but it is still difficult to predict the efficacy of individual patients and determine the best biological agents
.
Figure 2.
NNT comparison
of different psoriasis biologics and other partial therapeutic drugs The goal of further developing innovative therapeutic drugs is not only to enable more patients to achieve PASI 100 response, but also to help patients achieve disease remission, that is, to prevent recurrence after stopping treatment
。 Current research suggests that tissue intrinsic memory T cells (T RM Cells) may be the key to inflammation-mediated recurrence of skin diseases, and even after long-term systemic treatment, site-specific "disease memory" established by T RMcells may reactivate inflammation and lead to psoriasis recurrence [6], regulatory T cells (TRegCells) can also infiltrate into psoriasis plaques [7].
It is worth noting that the inflammatory factors such as IL-17 targeted in the treatment of psoriasis may also be involved in the disease process such as cancer and infection, so the impact of targeting these sites on treatment safety, potential therapeutic benefits, and traditional considerations such as disease activity, patient needs, doctors' experience, etc.
are all issues that need to be considered when selecting therapeutic drugs, and appropriate biomarkers are found to guide treatment.
It is a clinical need that is not met today and the direction of development in the future (see Figure 3).
In addition, comorbidities such as metabolic syndrome, (cardio)vascular and mental health disorders are challenges in the management of almost all chronic inflammatory skin diseases
.
Figure 3.
Considerations
for treatment decisions, Professor Diamant Thaci concluded, believing that in the next few years, the diagnosis and treatment of chronic inflammatory skin diseases will change significantly, resulting in further improvement in the quality of life of patients.
And this requires continuous progress
in precision medicine.
Re-examine the current status of RA treatment and look for unmet "pain points"
Professor Paul Emery's presentation topic was "Unmet Treatment Needs for RA", and Professor Paul Emery summarized the four major unmet treatment needs including: 1) better patient-reported outcomes (PROs), less pain and disability, including quality of life, 2) higher treatment response rate 3) maintenance of remission after slow tapering of medication 4) Prevention of arthritis first in order to achieve better PROs, reduce pain and disability, it is necessary to effectively control the disease activity of RA, studies have shown that pain is the most important cognition of disease activity in RA patients, but doctors often take the number of swollen joints as an evaluation criterion [8],
And many patients with RA still have significant pain
when disease activity is low.
In this case, drugs that target multiple sites and pathways can be selected, such as JAK inhibitors, which can directly or indirectly modulate signaling pathways related to inflammation and pain (see Figure 4), thereby effectively reducing pain while alleviating joint symptoms in RA patients [9].
Figure 4.
JAK inhibitors can directly or indirectly modulate signaling pathways
related to inflammation and pain, and in terms of achieving higher therapeutic response rates, with the continuous advancement of therapeutic drugs and the strong recommendation of authoritative guidelines, all patients with treatment-naïve RA should aim to achieve therapeutic remission, and drugs with higher
success rates should be selected as much as possible 。 Professor Paul Emery believes based on personal experience that the first-line treatment rate of traditional drugs such as methotrexate (MTX) has obviously not met the demand, and most patients in the real world cannot tolerate the full dose of MTX, and unsuccessful MTX treatment may also change the course of the disease, making it difficult to respond
to subsequent treatments.
Therefore, in order to achieve remission in more patients as early as possible, it is considered to predict response before treatment, as previous studies have shown that a lower baseline number of initial CD4+ T cells in patients with early RA can predict a lower response rate at six months of treatment [10].
Professor Paul Emery believes that in terms of drug reduction, the main patients who can be considered for reduction are patients who receive treatment early in the course of the disease, achieve deep remission early and can be maintained, in addition to no joint damage, normal function and good quality of life, young patients, low baseline disease activity, no glucocorticoids, seronegative and other factors can also be considered.
The above factors can be combined to formulate a clinical practical scoring system
to guide the reduction.
In addition, tapering
may be considered in patients who achieve a "multidimensional response" (MDR) as assessed by clinical symptoms, imaging, and immunomarkers, see Figure 5 。 A study led by Professor Paul Emery's team showed that about one-third of RA patients who achieved traditional DAS28 remission achieved MDR, and these patients reported better PROs overall, suggesting that MDR can be an ideal target for standard therapy (T2T) for RA patients from a patient perspective [11].
Figure 5.
The concept
of multidimensional response (MDR) For patients treated with bDMRADs, complete discontinuation is still not a realistic goal, considering that some patients may lose response when rebounding after treatment discontinuation should be considered, and only patients who have successfully achieved dose reduction should be considered for entering the discontinuation process
。 Available evidence suggests that bDMRADs may be considered for six months of clinical remission (normal CRP, zero number of swollen joints) and treated with MTX without glucocorticoids, and should be considered for discontinuation of bDMRADs only if symptoms do not worsen three months after the last reduction and there are good prognostic factors [12].
。
The last unmet therapeutic need is the prevention of arthritis, and in the past, whether screening people with anti-citrullinated protein antibodies (ACPA) positive or focusing on patients with clinically suspected arthralgia (CSA), was not enough to identify and intervene in the risk of RA "pre-clinical", so the current RA clinical diagnosis process focuses on three issues.
Namely: 1) identification of risk groups; 2) assess the risk of progression to RA; 3) Intervene to reduce risk
.
A national, observational study conducted by Professor Paul Emery's team, based on 10 years of data from the UK Primary Care Network, showed that patients with high anti-cyclic citrullinated peptide 2 antibody (CCP2) titers and hand or foot pain symptoms had a relatively highest risk of progression to RA, while patients without these two features had a low risk of progression (negative predictive value 96%) [13], which helps optimize the clinical diagnostic process and reduce delayed diagnosis
.
Another study showed that the use of third-generation anti-CCP3 antibodies was also more effective than anti-CCP2 antibodies in predicting the risk of disease progression in people at risk of RA [14].
In addition, many local factors also affect the microbial and mucosal immune status, which in turn affects the "local immunity" of RA patients, thus becoming the cause of RA, such as the high prevalence of periodontal disease in RA patients and ACPA-positive people (see Figure 6), and there are common risk factors such as smoking between the two, so it is necessary to pay attention to the risk of RA in patients with periodontal disease.
Interventions such as the treatment of Porphyromonas gingivalis are considered to delay or even prevent the onset of RA [15].
Fig.
6.
The prevalence of
periodontitis in healthy control population, CCP-positive RA risk group and early RA patients, and from the perspective of RA disease process, for anti-CCP antibody-positive people with skeletal muscle symptoms, ultrasound showed the presence of subclinical synovitis, May be a very predictive stage
in the disease process.
To prevent future joint lesions, it may not wait for typical joint symptoms in this group of people, but try to intervene
early.
A recent analysis by Professor Paul Emery's team showed that anti-CCP3 antibody positivity helps predict the progression of anti-CCP2 antibody-positive people to subclinical synovitis, meaning that screening antibody-positive people can provide a critical time window for early intervention (see Figure 7) [16].
Figure 7.
Time window for early intervention to prevent RA patients from progressing to arthritis
For medical professionals
only, PP-MG-CN-2667
References: [1]Ujiie H, Rosmarin D, Schön M P, et al.
Unmet medical needs in chronic, non-communicable inflammatory skin diseases[J].
Frontiers in Medicine, 2022: 875492.
[2]Satoh T K, Mellett M, Contassot E, et al.
Are neutrophilic dermatoses autoinflammatory disorders? [J].
British Journal of Dermatology, 2018, 178(3): 603-613.
[3]Griffiths CEM, et al.
Psoriasis.
Lancet 2021; 397:1301-15.
[4]Nast A, Smith C, Spuls P I, et al.
EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris–Part 1: treatment and monitoring recommendations[J].
Journal of the European Academy of Dermatology and Venereology, 2020, 34(11): 2461-2498.
[5]Sawyer L M, Malottki K, Sabry-Grant C, et al.
Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response[J].
PLoS One, 2019, 14(8): e0220868.
[6]Cheuk S, Wikén M, Blomqvist L, et al.
Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis[J].
The Journal of Immunology, 2014, 192(7): 3111-3120.
[7]Liu Y, Jarjour W, Olsen N, et al.
Traitor or warrior–Treg cells sneaking into the lesions of psoriatic arthritis[J].
Clinical Immunology, 2020, 215: 108425.
[8]Studenic P, Radner H, Smolen J S, et al.
Discrepancies between patients and physicians in their perceptions of rheumatoid arthritis disease activity[J].
Arthritis & Rheumatism, 2012, 64(9): 2814-2823.
[9]Simon L S, Taylor P C, Choy E H, et al.
The Jak/STAT pathway: A focus on pain in rheumatoid arthritis[C]//Seminars in Arthritis and Rheumatism.
WB Saunders, 2021, 51(1): 278-284.
[10]Ponchel F, Goëb V, Parmar R, et al.
An immunological biomarker to predict MTX response in early RA[J].
Annals of the Rheumatic Diseases, 2014, 73(11): 2047-2053.
[11]Gul H L, Eugenio G, Rabin T, et al.
Defining remission in rheumatoid arthritis: does it matter to the patient? A comparison of multi-dimensional remission criteria and patient reported outcomes[J].
Rheumatology, 2020, 59(3): 613-621.
[12]Liana Fraenkel,et al.
2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.
Arthritis Rheumatol .
2021 Jul; 73(7):1108-1123.
[13]Garcia-Montoya L, Nam J L, Duquenne L, et al.
Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study[J].
Arthritis Research & Therapy, 2022, 24: 26.
[14]Di Matteo A, Mankia K, Duquenne L, et al.
Third‐Generation Anti–Cyclic Citrullinated Peptide Antibodies Improve Prediction of Clinical Arthritis in Individuals at Risk of Rheumatoid Arthritis[J].
Arthritis & Rheumatology, 2020, 72(11): 1820-1828.
[15]Mankia K, Cheng Z, Do T, et al.
Prevalence of periodontal disease and periodontopathic bacteria in anti–cyclic citrullinated protein antibody–positive at-risk adults without arthritis[J].
JAMA Network Open, 2019, 2(6): e195394.
[16]Di Matteo A, Duquenne L, Cipolletta E, et al.
Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum[J].
Rheumatology, 2022, 61(8): 3192-3200.
This article is only for providing scientific information to healthcare professionals and does not represent the position of
the platform.
