Persistent low complement levels and increased interferon gene expression are predictive for disease progression in patients with incomplete systemic lupus erythematosus

Joint Bone Spine. 2022 Apr 29:105381. doi: 10.1016/j.jbspin.2022.105381. Online ahead of print.

NO ABSTRACT

PMID:35500799 | DOI:10.1016/j.jbspin.2022.105381

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A new avenue for treatment of chronic hand eczema

Br J Dermatol. 2022 May 1. doi: 10.1111/bjd.21604. Online ahead of print.

NO ABSTRACT

PMID:35490378 | DOI:10.1111/bjd.21604

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A new avenue for treatment of chronic hand eczema

Br J Dermatol. 2022 May 1. doi: 10.1111/bjd.21604. Online ahead of print.

NO ABSTRACT

PMID:35490378 | DOI:10.1111/bjd.21604

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Moderate-to-severe atopic dermatitis and lifestyle factors in the Dutch general population

Clin Exp Dermatol. 2022 Apr 5. doi: 10.1111/ced.15212. Online ahead of print.

ABSTRACT

BACKGROUND: Studies on the association between atopic dermatitis (AD) severity and lifestyle factors among adults have not been conducted in the Netherlands yet.

OBJECTIVES: To explore the association between moderate-to-severe AD and lifestyle factors among adults in the Dutch general population.

METHODS: We conducted this cross-sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135,950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between AD, moderate-to-severe AD and lifestyle factors using binary logistic regression and linear regression models.

RESULTS: We included 56,896 subjects (mean age 55.8 years, 39.7% males). The lifetime prevalence of self-reported physician-diagnosed AD was 9.1%. The point prevalence of AD was 3.3%, and the point prevalence of moderate-to-severe AD was 2.3%. We identified associations of moderate-to-severe AD with a smoking pack years of >15, an alcohol consumption of >2 drinks per day, chronic stress, class I obesity, and shorter and longer sleep duration. Moreover, we found dose-response associations with increased smoking pack years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality, and a vegetarian/vegan diet.

CONCLUSIONS: We found associations between moderate-to-severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors particularly smoking, alcohol use, stress, obesity, and sleep disturbances, appears warranted in patients with moderate-to-severe AD. Further longitudinal studies are required to better characterize the direction of these associations, and develop strategies for prevention.

PMID:35384028 | DOI:10.1111/ced.15212

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Moderate-to-severe atopic dermatitis and lifestyle factors in the Dutch general population

Clin Exp Dermatol. 2022 Apr 5. doi: 10.1111/ced.15212. Online ahead of print.

ABSTRACT

BACKGROUND: Studies on the association between atopic dermatitis (AD) severity and lifestyle factors among adults have not been conducted in the Netherlands yet.

OBJECTIVES: To explore the association between moderate-to-severe AD and lifestyle factors among adults in the Dutch general population.

METHODS: We conducted this cross-sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135,950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between AD, moderate-to-severe AD and lifestyle factors using binary logistic regression and linear regression models.

RESULTS: We included 56,896 subjects (mean age 55.8 years, 39.7% males). The lifetime prevalence of self-reported physician-diagnosed AD was 9.1%. The point prevalence of AD was 3.3%, and the point prevalence of moderate-to-severe AD was 2.3%. We identified associations of moderate-to-severe AD with a smoking pack years of >15, an alcohol consumption of >2 drinks per day, chronic stress, class I obesity, and shorter and longer sleep duration. Moreover, we found dose-response associations with increased smoking pack years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality, and a vegetarian/vegan diet.

CONCLUSIONS: We found associations between moderate-to-severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors particularly smoking, alcohol use, stress, obesity, and sleep disturbances, appears warranted in patients with moderate-to-severe AD. Further longitudinal studies are required to better characterize the direction of these associations, and develop strategies for prevention.

PMID:35384028 | DOI:10.1111/ced.15212

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Pathophysiology of transient neurological deficit in patients with chronic subdural hematoma: A systematic review

Acta Neurol Scand. 2022 Mar 31. doi: 10.1111/ane.13617. Online ahead of print.

ABSTRACT

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH.

PMID:35355247 | DOI:10.1111/ane.13617

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Pathophysiology of transient neurological deficit in patients with chronic subdural hematoma: A systematic review

Acta Neurol Scand. 2022 Jun;145(6):649-657. doi: 10.1111/ane.13617. Epub 2022 Mar 31.

ABSTRACT

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH.

PMID:35355247 | DOI:10.1111/ane.13617

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International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis

JAMA Dermatol. 2022 Mar 30. doi: 10.1001/jamadermatol.2022.0434. Online ahead of print.

ABSTRACT

IMPORTANCE: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.

OBJECTIVE: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.

DESIGN, SETTING, AND PARTICIPANTS: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).

MAIN OUTCOMES AND MEASURES: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.

RESULTS: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.

CONCLUSIONS AND RELEVANCE: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

PMID:35353175 | DOI:10.1001/jamadermatol.2022.0434

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Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

JAMA Dermatol. 2022 Mar 30. doi: 10.1001/jamadermatol.2022.0290. Online ahead of print.

ABSTRACT

IMPORTANCE: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic.

OBJECTIVE: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed.

EXPOSURES: The disease course and clinical characteristics of orf-induced immunobullous disease were observed.

MAIN OUTCOMES AND MEASURES: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease.

RESULTS: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The ?3, ?3, and ?2 chains were recognized in 2, 4, and 1 patient(s), respectively.

CONCLUSIONS AND RELEVANCE: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity.

PMID:35353128 | DOI:10.1001/jamadermatol.2022.0290

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Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

JAMA Dermatol. 2022 Mar 30:e220290. doi: 10.1001/jamadermatol.2022.0290. Online ahead of print.

ABSTRACT

IMPORTANCE: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic.

OBJECTIVE: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed.

EXPOSURES: The disease course and clinical characteristics of orf-induced immunobullous disease were observed.

MAIN OUTCOMES AND MEASURES: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease.

RESULTS: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The ?3, ?3, and ?2 chains were recognized in 2, 4, and 1 patient(s), respectively.

CONCLUSIONS AND RELEVANCE: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity.

PMID:35353128 | PMC:PMC8968717 | DOI:10.1001/jamadermatol.2022.0290

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International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis

JAMA Dermatol. 2022 Mar 30. doi: 10.1001/jamadermatol.2022.0434. Online ahead of print.

ABSTRACT

IMPORTANCE: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.

OBJECTIVE: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.

DESIGN, SETTING, AND PARTICIPANTS: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).

MAIN OUTCOMES AND MEASURES: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.

RESULTS: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.

CONCLUSIONS AND RELEVANCE: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

PMID:35353175 | DOI:10.1001/jamadermatol.2022.0434

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Functional investigation of two simultaneous or separately segregating DSP variants within a single family support the theory of a dose-dependent disease severity

Exp Dermatol. 2022 Mar 24. doi: 10.1111/exd.14571. Online ahead of print.

ABSTRACT

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated. Here, we describe and have performed RNA, protein and tissue analysis in a large family where DSPc.273+5G>A/c.6687delA segregated with palmoplantar keratoderma (PPK), woolly hair and lethal cardiomyopathy, while DSPWT/c.6687delA segregated with PPK and milder cardiomyopathy. hiPSC-derived cardiomyocytes and primary keratinocytes from carriers were obtained for analysis. Unlike the previously reported nonsense variants in the last exon of DSP that bypassed the nonsense-mediated mRNA surveillance system leading to protein truncation, variant c.6687delA was shown to cause loss of protein expression. Patients carrying both variants and having a considerably more severe phenotype were shown to have 70% DP protein reduction, while patients carrying only c.6687delA had 50% protein reduction and a milder phenotype. Analysis of RNA from patient cells did not show any splicing effect of the c.273+5G>A variant. However, a minigene splicing assay clearly showed alternative spliced transcripts originating from this variant. This study shows the importance of RNA and protein analyses to pinpoint the exact effect of DSP variants instead of solely relying on predictions. In addition, the particular pattern of inheritance, with simultaneous or separately segregating DSP variants within the same family, strongly supports the theory of a dose-dependent disease severity.

PMID:35325485 | DOI:10.1111/exd.14571

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Functional investigation of two simultaneous or separately segregating DSP variants within a single family supports the theory of a dose-dependent disease severity

Exp Dermatol. 2022 Mar 24. doi: 10.1111/exd.14571. Online ahead of print.

ABSTRACT

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over the years, many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated. Here, we describe and have performed RNA, protein and tissue analysis in a large family where DSPc.273+5G>A/c.6687delA segregated with palmoplantar keratoderma (PPK), woolly hair and lethal cardiomyopathy, while DSPWT/c.6687delA segregated with PPK and milder cardiomyopathy. hiPSC-derived cardiomyocytes and primary keratinocytes from carriers were obtained for analysis. Unlike the previously reported nonsense variants in the last exon of DSP that bypassed the nonsense-mediated mRNA surveillance system leading to protein truncation, variant c.6687delA was shown to cause the loss of protein expression. Patients carrying both variants and having a considerably more severe phenotype were shown to have 70% DP protein reduction, while patients carrying only c.6687delA had 50% protein reduction and a milder phenotype. The analysis of RNA from patient cells did not show any splicing effect of the c.273+5G>A variant. However, a minigene splicing assay clearly showed alternative spliced transcripts originating from this variant. This study shows the importance of RNA and protein analyses to pinpoint the exact effect of DSP variants instead of solely relying on predictions. In addition, the particular pattern of inheritance, with simultaneous or separately segregating DSP variants within the same family, strongly supports the theory of a dose-dependent disease severity.

PMID:35325485 | DOI:10.1111/exd.14571

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Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study

Lancet Rheumatol. 2022 Mar 17. doi: 10.1016/S2665-9913(22)00034-0. Online ahead of print.

ABSTRACT

BACKGROUND: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.

METHODS: We did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses-ie, vaccination after previous SARS-CoV-2 infection-were studied as a proxy for recall responses.

FINDINGS: Between Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19-0·49] for anti-CD20 therapy, 0·35 [0·21-0·55] for S1P modulators, and 0·61 [0·40-0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment.

INTERPRETATION: Humoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited.

FUNDING: ZonMw (The Netherlands Organization for Health Research and Development).

PMID:35317410 | PMC:PMC8930018 | DOI:10.1016/S2665-9913(22)00034-0

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Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study

Lancet Rheumatol. 2022 May;4(5):e338-e350. doi: 10.1016/S2665-9913(22)00034-0. Epub 2022 Mar 17.

ABSTRACT

BACKGROUND: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.

METHODS: We did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses-ie, vaccination after previous SARS-CoV-2 infection-were studied as a proxy for recall responses.

FINDINGS: Between Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19-0·49] for anti-CD20 therapy, 0·35 [0·21-0·55] for S1P modulators, and 0·61 [0·40-0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment.

INTERPRETATION: Humoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited.

FUNDING: ZonMw (The Netherlands Organization for Health Research and Development).

PMID:35317410 | PMC:PMC8930018 | DOI:10.1016/S2665-9913(22)00034-0

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