212 results on '"Immune-mediated inflammatory disease"'
Search Results
2. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study.
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Hitchon, Carol A, Bowdish, Dawn M. E., Boire, Gilles, Fortin, Paul R., Flamand, Louis, Chandran, Vinod, Dayam, Roya M., Gingras, Anne-Claude, Card, Catherine M., Colmegna, Inés, Larché, Maggie J., Kaplan, Gilaad G., Lukusa, Luck, Lee, Jennifer L.F., and Bernatsky, Sasha
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INFLAMMATORY bowel diseases ,TUMOR necrosis factors ,COVID-19 pandemic ,COVID-19 vaccines ,LOGISTIC regression analysis - Abstract
Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab's results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data.
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Merola, Joseph F., Ertmer, Brennan, Liang, Huifang, Yue, Xiaomeng, Ofori, Sarah, and Krueger, Whitney
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Certain immune-mediated inflammatory diseases (IMIDs) may increase patients' risk for venous thromboembolisms (VTEs), yet how atopic dermatitis (AD) influences VTE risk remains unclear. Describe VTE incidence in patients with AD compared with other IMIDs and unaffected, AD-matched controls. This retrospective, observational, comparative cohort study used Optum Clinformatics United States claims data (2010-2019) of adults with AD, rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). Unaffected control patients were matched 1:1 with patients with AD. Of 2,061,222 patients with IMIDs, 1,098,633 had AD. Patients with AD had a higher VTE incidence (95% CI) than did unaffected, AD-matched controls (0.73 [0.72-0.74] versus 0.59 [0.58-0.60] cases/100 person-years). When controlling for baseline VTE risk factors, however, AD was not associated with increased VTE risk (HR 0.96 [0.90-1.02]). VTE risk was lower in patients with AD versus RA, UC, CD, AS, or PsA; VTE risk was similar to patients with PsO. Disease activity and severity were not accounted for. AD did not increase VTE risk when accounting for underlying risk factors. AD was associated with lower VTE risk compared with several rheumatologic and gastrointestinal IMIDs. [ABSTRACT FROM AUTHOR]
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- 2024
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4. scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
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Samuel Schäfer, Martin Smelik, Oleg Sysoev, Yelin Zhao, Desiré Eklund, Sandra Lilja, Mika Gustafsson, Holger Heyn, Antonio Julia, István A. Kovács, Joseph Loscalzo, Sara Marsal, Huan Zhang, Xinxiu Li, Danuta Gawel, Hui Wang, and Mikael Benson
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Single-cell RNA sequencing ,scRNA-seq ,Immune-mediated inflammatory disease ,Drug prioritisation ,Drug repurposing ,Drug prediction ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. Methods Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs. Results scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Conclusions We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package ( https://github.com/SDTC-CPMed/scDrugPrio ).
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- 2024
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5. Contraceptive Recommendations for Women with Immune-Mediated Inflammatory Diseases: A Delphi Consensus.
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Carrascosa, José Manuel, Echarri, Ana, Gavín Sebastián, Olga, García de la Peña, Paloma, Martínez Pérez, Oscar, Ramirez, Susan, Valderrama, Mónica, and Montoro Álvarez, María
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Introduction: Immune-mediated inflammatory diseases (IMID) are a group of disorders characterized by chronic inflammation caused by an altered immune regulation in targeted organs or systems. IMID itself could have an implied increased risk of venous thromboembolism (VTE) and this risk varies throughout the course of the disease as well as with some contraceptive methods and treatments. The aim of this study was to present some key considerations in relation to contraception in women with IMID. Methods: This was an exploratory study conducted in Spain following the online modified Delphi methodology with two rounds of participation. Four questionnaires were designed for each medical specialty: gastroenterology, rheumatology, dermatology, and gynecology. Each questionnaire was divided in three domains: general recommendations about IMID, specific recommendations, and contraceptive methods for patients with IMID. A 5-point Likert scale measured agreement with each statement, with an 80% agreement threshold. Following the first round, the percentage of each response was calculated for every item. Subsequently, a second round was conducted to reach a consensus on the items for which discrepancies were observed. Results: A total of 52 and 50 experts participated in the first and second round, respectively. Participants agreed on the existence of a higher risk of VTE in inflammatory bowel diseases, psoriasis, and rheumatoid arthritis diseases. Regarding recommendations for contraceptive methods in patients with IMID, experts considered the hormonal intrauterine device (IUD) as a first-line contraceptive (80.0%) and low doses of progesterone-only pills if the latter is not recommended (88.0%). Most of the interviewees concurred on the importance of the patients' contraceptive needs during the disease course (98.1%). Conclusion: Raising awareness and promoting a multidisciplinary relationship among the physicians involved in the therapeutic decisions by considering all the risk factors when prescribing a contraceptive method is important to prevent VTE in women with IMID. [ABSTRACT FROM AUTHOR]
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- 2024
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6. scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases.
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Schäfer, Samuel, Smelik, Martin, Sysoev, Oleg, Zhao, Yelin, Eklund, Desiré, Lilja, Sandra, Gustafsson, Mika, Heyn, Holger, Julia, Antonio, Kovács, István A., Loscalzo, Joseph, Marsal, Sara, Zhang, Huan, Li, Xinxiu, Gawel, Danuta, Wang, Hui, and Benson, Mikael
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TRANSCRIPTOMES , *CROHN'S disease , *INDIVIDUALIZED medicine , *PSORIATIC arthritis , *DRUG repositioning - Abstract
Background: Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. Methods: Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs. Results: scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn's disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn's disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Conclusions: We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio's potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio). [ABSTRACT FROM AUTHOR]
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- 2024
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- View/download PDF
7. COVID-19 vaccination of patients with chronic immune-mediated inflammatory disease
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Wen Yanfang, Chen Jianfeng, Liu Changlian, and Wang Yan
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Immune-mediated inflammatory disease ,COVID-19 vaccine ,Safety ,Efficacy ,Diseases of the musculoskeletal system ,RC925-935 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Objective This study aimed to analyze the safety and efficacy of COVID-19 vaccines among patients with chronic immune-mediated inflammatory disease (IMID) in China. Methods Participants who were diagnosed with a chronic IMID were eligible for inclusion in this study. Age- and sex-matched healthy vaccinated individuals were set as the control group. All participants received two doses of the inactivated CoronaVac vaccine or three doses of the recombinant protein subunit vaccine ZF2001. Adverse events, IMID activity after vaccination, and the rate of COVID-19 in the two groups were compared. Results There were 158 patients in the IMID group, with an average age of 40 ± 14 years old, and 98 female subjects. In the IMID group, 123 patients received the inactivated CoronaVac vaccine, and 35 patients received the recombinant protein subunit vaccine ZF2001. There were 153 individuals in the control group, including 122 who received the CoronaVac vaccine and 31 who received the recombinant protein subunit vaccine ZF2001. The frequency of vaccine-related adverse events in the IMID group was less than that in the control group, all of which were mild local effects, and no serious events occurred. Of note, no disease flares occurred in the IMID group. No participants in either group subsequently got COVID-19, so the incidence rate was 0% in both groups. Conclusion COVID-19 vaccination was found to be safe for IMID subjects, any adverse events were mild, and vaccination did not increase the risk of disease activity. Meanwhile, vaccination could effectively reduce the incidence of COVID-19 in IMID patients. In the future, studies with a larger sample size and a longer duration are needed.
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- 2023
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8. Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study
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Carol A Hitchon, Dawn M. E. Bowdish, Gilles Boire, Paul R. Fortin, Louis Flamand, Vinod Chandran, Roya M. Dayam, Anne-Claude Gingras, Catherine M. Card, Inés Colmegna, Maggie J. Larché, Gilaad G. Kaplan, Luck Lukusa, Jennifer L.F. Lee, Sasha Bernatsky, and on behalf of the SUCCEED Investigative Team
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COVID-19 ,vaccination ,immune-mediated inflammatory disease ,methotrexate ,tumor necrosis factor inhibitors ,autoimmune diseases ,Medicine - Abstract
Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab’s results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.
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- 2024
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9. Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.
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Joyees, Jerlin, Marrie, Ruth Ann, Bernstein, Charles N., Bolton, James M., Fisk, John D., Graff, Lesley A., Hitchon, Carol, Patten, Scott B., and Kowalec, Kaarina
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INFLAMMATORY bowel diseases ,RHEUMATOID arthritis ,MULTIPLE sclerosis ,ANXIETY ,MENTAL depression - Abstract
Introduction: Immune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex. Methods: Participants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID. Results: Of 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females. Discussion: We found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findingscould be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project
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Ylenia Ingrasciotta, Andrea Spini, Luca L'Abbate, Elena Sofia Fiore, Massimo Carollo, Valentina Ientile, Valentina Isgrò, Anna Cavazzana, Valeria Biasi, Paola Rossi, Lucian Ejlli, Valeria Belleudi, Francesca Poggi, Ester Sapigni, Aurora Puccini, Domenica Ancona, Paolo Stella, Sebastiano Pollina Addario, Alessandra Allotta, Olivia Leoni, Martina Zanforlini, Marco Tuccori, Rosa Gini, and Gianluca Trifirò
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External validity ,Immune-mediated inflammatory disease ,Pivotal randomized clinical trial ,Representativeness ,Generalizability ,Biological drugs ,Therapeutics. Pharmacology ,RM1-950 - Abstract
To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients’ characteristics and median treatment duration of biologics approved for IMIDs between RCTs’ and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8–1.9) compared to RCTs (F/M ratio: 0.5–0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4–100 vs. 6–167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.
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- 2024
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11. Real‐world drug survival of Brodalumab, in patients with psoriasis switched from Ixekizumab: Results of a single centre retrospective study (BroSwitch)
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Jolijn C. Bethlem, Jenny A. H. M. Janssens, and Milan Tjioe
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biological ,immune‐mediated inflammatory disease ,Psoriasis ,Dermatology ,RL1-803 ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Biologicals are a widely used treatment for psoriasis (PsO), however, biologicals are expensive and while continuous use is warranted, sometimes need switching. In January 2021, dermatologists of Bravis Hospital and dermaTeam clinic actively switched 91 patients, who received Ixekizumab, to Brodalumab due to health economic reasons. This is a retrospective, real‐world cohort study. Objectives This study aimed to assess Brodalumab drug survival, reasons for discontinuing Brodalumab and side effects. The researchers also hoped to gain insight into determinants for Brodalumab drug survival. Methods Data were retrospectively extracted from electronic medical records (EMR). Psoriasis Area Severity Index (PASI) scores were evaluated. Drug survival was analysed using Kaplan–Meier estimates. Analyses were split according to the reason for discontinuing: primary or secondary ineffectiveness, and side effects. Results A total of 91 EMRs were included. Overall, 29 patients (32%) discontinued Brodalumab within 1 year owing to: primary inefficacy (45%), secondary inefficacy (31%), only side effects (14%), or other reasons (10%). The most reported side effect was xerosis cutis, followed by joint pain. PASI scores were lacking. No determinants to make switching more successful were found. Drug survival was 53% at Week 50. Conclusions Drug survival of Brodalumab after switch from Ixekizumab in our patient group was low at 53%. Inadequate disease control was more important than side effects.
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- 2023
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12. Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis
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Jerlin Joyees, Ruth Ann Marrie, Charles N. Bernstein, James M. Bolton, John D. Fisk, Lesley A. Graff, Carol Hitchon, Scott B. Patten, Kaarina Kowalec, for the CIHR team in defining the burden and managing the effects of psychiatric comorbidity in chronic immunoinflammatory disease, Lesley Graff, John R. Walker, Carol A. Hitchon, Lisa M. Lix, James Bolton, Jitender Sareen, Alan Katz, James J. Marriott, Alexander Singer, Renée El-Gabalawy, Christine A. Peschken, Ryan Zarychanski, and Lindsay I. Berrigan
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anxiety ,sex ,immune-mediated inflammatory disease ,multiple sclerosis ,rheumatoid arthritis ,inflammatory bowel disease ,Psychiatry ,RC435-571 - Abstract
IntroductionImmune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex.MethodsParticipants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID.ResultsOf 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females.DiscussionWe found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findings could be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID.
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- 2023
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13. New-Onset Rheumatic Immune-Mediated Inflammatory Diseases Following SARS-CoV-2 Vaccinations until May 2023: A Systematic Review.
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Nune, Arvind, Durkowski, Victor, Pillay, S. Sujitha, Barman, Bhupen, Elwell, Helen, Bora, Kaustubh, Bilgrami, Syed, Mahmood, Sajid, Babajan, Nasarulla, Venkatachalam, Srinivasan, Ottewell, Lesley, and Manzo, Ciro
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CONNECTIVE tissue diseases ,VACCINATION ,INTRAVENOUS immunoglobulins ,SARS-CoV-2 ,COVID-19 vaccines - Abstract
A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking. Therefore, we investigated the demographics, management, and prognosis of new R-IMIDs in adults following SARS-CoV-2 vaccinations. A systematic literature search of Medline, Embase, Google Scholar, LitCovid, and Cochrane was conducted. We included any English-language study that reported new-onset R-IMID in adults following the post-COVID-19 vaccination. A total of 271 cases were reported from 39 countries between January 2021 and May 2023. The mean age of patients was 56 (range 18–90), and most were females (170, 62.5%). Most (153, 56.5%) received the Pfizer BioNTech COVID-19 vaccine. Nearly 50% of patients developed R-IMID after the second dose of the vaccine. Vasculitis was the most prevalent clinical presentation (86, 31.7%), followed by connective tissue disease (66, 24.3%). The mean duration between the vaccine's 'trigger' dose and R-IMID was 11 days. Most (220, 81.2%) received corticosteroids; however, 42% (115) received DMARDs such as methotrexate, cyclophosphamide, tocilizumab, anakinra, IV immunoglobulins, plasma exchange, or rituximab. Complete remission was achieved in 75 patients (27.7%), and 137 (50.6%) improved following the treatment. Two patients died due to myositis. This SR highlights that SARS-CoV-2 vaccines may trigger R-IMID; however, further epidemiology studies are required. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Susceptibility to COVID-19 and Immunologic Response to Vaccination in Patients With Immune-Mediated Inflammatory Diseases.
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Finckh, Axel, Ciurea, Adrian, Raptis, Catherine E, and Rubbert-Roth, Andrea
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COVID-19 pandemic , *INFLAMMATORY bowel diseases , *VACCINATION , *COVID-19 vaccines , *RHEUMATOID arthritis - Abstract
Immune-mediated inflammatory diseases (IMIDs) are a highly heterogeneous group of diseases that share a common etiology of immune dysregulation, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, among others. It is estimated that the prevalence of IMIDs ranges between 5% and 7% in developed countries. As current management of IMIDs includes the use of immunomodulatory medications, the resulting weakened immune response can increase the risk of infection, including with SARS-CoV-2 (the causative agent of COVID-19) and reduce response to vaccination, placing these individuals at continued risk of severe outcomes from COVID-19. In this article, we summarize the current literature related to COVID-19 outcomes and the immunogenicity and reactogenicity of COVID-19 mRNA vaccination among patients with rheumatologically dominated IMIDs, as well as the effect of immunomodulatory therapies on these outcomes. We conclude by providing current COVID-19 vaccination recommendations for individuals with IMID. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Deciphering global trends in immune‐mediated inflammatory diseases: A three‐decade epidemiological journey
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Dongze Wu, Yingzhao Jin, and Lai‐shan Tam
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immune‐mediated inflammatory disease ,incidence ,global burden of disease study ,trend ,Immunologic diseases. Allergy ,RC581-607 ,Diseases of the musculoskeletal system ,RC925-935 - Published
- 2024
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16. Blockade of IL-18Rα-mediated signaling pathway exacerbates neutrophil infiltration in imiquimod-induced psoriasis murine model
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Hiroki Akazawa, Yuji Nozaki, Hirotaka Yamazawa, Kaori Ishimura, Chisato Ashida, Akinori Okada, Koji Kinoshita, and Itaru Matsumura
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immune-mediated inflammatory disease ,psoriasis ,IL-18Rα ,neutrophil ,innate immunity ,Medicine (General) ,R5-920 - Abstract
Psoriasis is an immune-mediated inflammatory disease of the skin, which is characterized by epidermal hyperkeratosis and neutrophil infiltration. The interleukin (IL)-17/IL-23 pathway and associated cytokines play major roles in the pathogenesis and exacerbation of psoriasis. The IL-18/IL-18 receptor (R) α signaling pathway is important for Th1 cytokine production and differentiation of Th1 cells; however, its role in the pathogenesis of psoriasis remains unknown. In this study, we investigated the effect of the IL-18Rα-mediated signaling pathway in the pathogenesis of psoriasis in Il18ra-deficient mice (Il18ra−/−) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. Il18ra deficiency led to significant increases in the levels of IL-1β, IL-6, IL-8, IL-17A, IL-23, and chemokine (C-X-C motif) ligand 2 in skin lesions. Gr1-positive cells highly infiltrated psoriatic skin lesions in Il18ra−/− mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in Il18ra−/− mice. These results suggest that IL-18Rα-mediated signaling pathways may inhibit psoriatic skin inflammation by regulating infiltration and activation of neutrophil and other innate immune cells.
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- 2023
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17. Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019Research in context
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Dongze Wu, Yingzhao Jin, Yuhan Xing, Melsew Dagne Abate, Mohammadreza Abbasian, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Foad Abd-Allah, Michael Abdelmasseh, Mohammad-Amin Abdollahifar, Deldar Morad Abdulah, Aidin Abedi, Vida Abedi, Hassan Abidi, Richard Gyan Aboagye, Hassan Abolhassani, Katrina Abuabara, Morteza Abyadeh, Isaac Yeboah Addo, Kayode Nelson Adeniji, Abiola Victor Adepoju, Miracle Ayomikun Adesina, Qorinah Estiningtyas Sakilah Adnani, Mohsen Afarideh, Shahin Aghamiri, Antonella Agodi, Anurag Agrawal, Constanza Elizabeth Aguilera Arriagada, Aqeel Ahmad, Danish Ahmad, Sajjad Ahmad, Sohail Ahmad, Ali Ahmadi, Ali Ahmed, Ayman Ahmed, Janardhana P. Aithala, Abdullateef Abiodun Ajadi, Marjan Ajami, Mostafa Akbarzadeh-Khiavi, Fares Alahdab, Mohammad T. AlBataineh, Sharifullah Alemi, Adel Ali Saeed Al-Gheethi, Liaqat Ali, Sheikh Mohammad Alif, Joseph Uy Almazan, Sami Almustanyir, Jaber S. Alqahtani, Ibrahim Alqasmi, Ihsan Ullah Khan Altaf, Nelson Alvis-Guzman, Nelson J. Alvis-Zakzuk, Yaser Mohammed Al-Worafi, Hany Aly, Reza Amani, Hubert Amu, Ganiyu Adeniyi Amusa, Catalina Liliana Andrei, Adnan Ansar, Hossein Ansariniya, Anayochukwu Edward Anyasodor, Jalal Arabloo, Reza Arefnezhad, Judie Arulappan, Mohammad Asghari-Jafarabadi, Tahira Ashraf, Jamila Abdulhamid Atata, Seyyed Shamsadin Athari, Daniel Atlaw, Maha Moh'd Wahbi Atout, Avinash Aujayeb, Asma Tahir Awan, Haleh Ayatollahi, Sina Azadnajafabad, Ahmed Y. Azzam, Alaa Badawi, Ashish D. Badiye, Sara Bagherieh, Atif Amin Baig, Berihun Bantie Bantie, Martina Barchitta, Mainak Bardhan, Suzanne Lyn Barker-Collo, Francesco Barone-Adesi, Kavita Batra, Nebiyou Simegnew Bayileyegn, Amir Hossein Behnoush, Uzma Iqbal Belgaumi, Maryam Bemanalizadeh, Isabela M. Bensenor, Kebede A. Beyene, Akshaya Srikanth Bhagavathula, Pankaj Bhardwaj, Sonu Bhaskar, Ajay Nagesh Bhat, Saeid Bitaraf, Veera R. Bitra, Archith Boloor, Kaustubh Bora, João Silva Botelho, Rachelle Buchbinder, Daniela Calina, Luis Alberto Cámera, Andre F. Carvalho, Jeffrey Shi Kai Chan, Vijay Kumar Chattu, Endeshaw Chekol Abebe, Fatemeh Chichagi, Sungchul Choi, Tzu-Chieh Chou, Dinh-Toi Chu, Kaleb Coberly, Vera Marisa Costa, Rosa A.S. Couto, Natália Cruz-Martins, Omid Dadras, Xiaochen Dai, Giovanni Damiani, Ana Maria Dascalu, Mohsen Dashti, Sisay Abebe Debela, Robert Paul Dellavalle, Andreas K. Demetriades, Alemayehu Anley Demlash, Xinlei Deng, Hardik Dineshbhai Desai, Rupak Desai, Syed Masudur Rahman Dewan, Sourav Dey, Samath Dhamminda Dharmaratne, Daniel Diaz, Mahmoud Dibas, Ricardo Jorge Dinis-Oliveira, Mengistie Diress, Thanh Chi Do, Duy Khanh Doan, Masoud Dodangeh, Milad Dodangeh, Deepa Dongarwar, John Dube, Arkadiusz Marian Dziedzic, Abdelaziz Ed-Dra, Hisham Atan Edinur, Negin Eissazade, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Noha Mousaad Elemam, Muhammed Elhadi, Ahmed O. Elmehrath, Omar Abdelsadek Abdou Elmeligy, Mehdi Emamverdi, Theophilus I. Emeto, Hawi Leul Esayas, Habitu Birhan Eshetu, Farshid Etaee, Adeniyi Francis Fagbamigbe, Shahriar Faghani, Ildar Ravisovich Fakhradiyev, Ali Fatehizadeh, Mobina Fathi, Alireza Feizkhah, Ginenus Fekadu, Mohammad Fereidouni, Seyed-Mohammad Fereshtehnejad, João C. Fernandes, Pietro Ferrara, Getahun Fetensa, Irina Filip, Florian Fischer, Behzad Foroutan, Masoud Foroutan, Takeshi Fukumoto, Balasankar Ganesan, Belete Negese Belete Gemeda, Seyyed-Hadi Ghamari, MohammadReza Ghasemi, Maryam Gholamalizadeh, Tiffany K. Gill, Richard F. Gillum, Mohamad Goldust, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Houman Goudarzi, Shi-Yang Guan, Yang Guo, Bhawna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Rasool Haddadi, Najah R. Hadi, Rabih Halwani, Shafiul Haque, Ikramul Hasan, Reza Hashempour, Amr Hassan, Treska S. Hassan, Sara Hassanzadeh, Mohammed Bheser Hassen, Johannes Haubold, Khezar Hayat, Golnaz Heidari, Mohammad Heidari, Reza Heidari-Soureshjani, Claudiu Herteliu, Kamran Hessami, Kamal Hezam, Yuta Hiraike, Ramesh Holla, Mohammad-Salar Hosseini, Hong-Han Huynh, Bing-Fang Hwang, Segun Emmanuel Ibitoye, Irena M. Ilic, Milena D. Ilic, Arad Iranmehr, Farideh Iravanpour, Nahlah Elkudssiah Ismail, Masao Iwagami, Chidozie C.D. Iwu, Louis Jacob, Morteza Jafarinia, Abdollah Jafarzadeh, Kasra Jahankhani, Haitham Jahrami, Mihajlo Jakovljevic, Elham Jamshidi, Chinmay T. Jani, Manthan Dilipkumar Janodia, Sathish Kumar Jayapal, Shubha Jayaram, Jayakumar Jeganathan, Jost B. Jonas, Abel Joseph, Nitin Joseph, Charity Ehimwenma Joshua, K. Vaishali, Billingsley Kaambwa, Ali Kabir, Zubair Kabir, Vidya Kadashetti, Feroze Kaliyadan, Fatemeh Kalroozi, Vineet Kumar Kamal, Amit Kandel, Himal Kandel, Srikanta Kanungo, Jafar Karami, Ibraheem M. Karaye, Hanie Karimi, Hengameh Kasraei, Sina Kazemian, Sewnet Adem Kebede, Leila Keikavoosi-Arani, Mohammad Keykhaei, Yousef Saleh Khader, Himanshu Khajuria, Faham Khamesipour, Ejaz Ahmad Khan, Imteyaz A. Khan, Maseer Khan, Md Jobair Khan, Moien A.B. Khan, Muhammad Arslan Khan, Haitham Khatatbeh, Moawiah Mohammad Khatatbeh, Sorour Khateri, Hamid Reza Khayat Kashani, Min Seo Kim, Adnan Kisa, Sezer Kisa, Hyun Yong Koh, Pavel Kolkhir, Oleksii Korzh, Ashwin Laxmikant Kotnis, Parvaiz A. Koul, Ai Koyanagi, Kewal Krishan, Mohammed Kuddus, Vishnutheertha Vishnutheertha Kulkarni, Narinder Kumar, Satyajit Kundu, Om P. Kurmi, Carlo La Vecchia, Chandrakant Lahariya, Tri Laksono, Judit Lám, Kamaluddin Latief, Paolo Lauriola, Basira Kankia Lawal, Thao Thi Thu Le, Trang Thi Bich Le, Munjae Lee, Seung Won Lee, Wei-Chen Lee, Yo Han Lee, Jacopo Lenzi, Miriam Levi, Wei Li, Virendra S. Ligade, Stephen S. Lim, Gang Liu, Xuefeng Liu, Erand Llanaj, Chun-Han Lo, Vanessa Sintra Machado, Azzam A. Maghazachi, Mansour Adam Mahmoud, Tuan A. Mai, Azeem Majeed, Pantea Majma Sanaye, Omar Mohamed Makram, Elaheh Malakan Rad, Kashish Malhotra, Ahmad Azam Malik, Iram Malik, Tauqeer Hussain Mallhi, Deborah Carvalho Malta, Mohammad Ali Mansournia, Lorenzo Giovanni Mantovani, Miquel Martorell, Sahar Masoudi, Seyedeh Zahra Masoumi, Yasith Mathangasinghe, Elezebeth Mathews, Alexander G. Mathioudakis, Andrea Maugeri, Mahsa Mayeli, John Robert Carabeo Medina, Gebrekiros Gebremichael Meles, José João Mendes, Ritesh G. Menezes, Tomislav Mestrovic, Irmina Maria Michalek, Ana Carolina Micheletti Gomide Nogueira de Sá, Ephrem Tesfaye Mihretie, Le Huu Nhat Minh, Reza Mirfakhraie, Erkin M. Mirrakhimov, Awoke Misganaw, Ashraf Mohamadkhani, Nouh Saad Mohamed, Faezeh Mohammadi, Soheil Mohammadi, Salahuddin Mohammed, Shafiu Mohammed, Syam Mohan, Anita Mohseni, Ali H. Mokdad, Sara Momtazmanesh, Lorenzo Monasta, Mohammad Ali Moni, Md Moniruzzaman, Yousef Moradi, Negar Morovatdar, Ebrahim Mostafavi, Parsa Mousavi, George Duke Mukoro, Admir Mulita, Getaneh Baye Mulu, Efrén Murillo-Zamora, Fungai Musaigwa, Ghulam Mustafa, Sathish Muthu, Firzan Nainu, Vinay Nangia, Sreenivas Narasimha Swamy, Zuhair S. Natto, Perumalsamy Navaraj, Biswa Prakash Nayak, Athare Nazri-Panjaki, Hadush Negash, Mohammad Hadi Nematollahi, Dang H. Nguyen, Hau Thi Hien Nguyen, Hien Quang Nguyen, Phat Tuan Nguyen, Van Thanh Nguyen, Robina Khan Niazi, Taxiarchis Konstantinos Nikolouzakis, Lawrence Achilles Nnyanzi, Mamoona Noreen, Chimezie Igwegbe Nzoputam, Ogochukwu Janet Nzoputam, Bogdan Oancea, In-Hwan Oh, Hassan Okati-Aliabad, Osaretin Christabel Okonji, Patrick Godwin Okwute, Andrew T. Olagunju, Matthew Idowu Olatubi, Isaac Iyinoluwa Olufadewa, Michal Ordak, Nikita Otstavnov, Mayowa O. Owolabi, P.A. Mahesh, Jagadish Rao Padubidri, Anton Pak, Reza Pakzad, Raffaele Palladino, Adrian Pana, Ioannis Pantazopoulos, Paraskevi Papadopoulou, Shahina Pardhan, Ashwaghosha Parthasarathi, Ava Pashaei, Jay Patel, Aslam Ramjan Pathan, Shankargouda Patil, Uttam Paudel, Shrikant Pawar, Paolo Pedersini, Umberto Pensato, David M. Pereira, Jeevan Pereira, Maria Odete Pereira, Renato B. Pereira, Mario F.P. Peres, Arokiasamy Perianayagam, Simone Perna, Ionela-Roxana Petcu, Parmida Sadat Pezeshki, Hoang Tran Pham, Anil K. Philip, Michael A. Piradov, Indrashis Podder, Vivek Podder, Dimitri Poddighe, Elton Junio Sady Prates, Ibrahim Qattea, Amir Radfar, Pourya Raee, Alireza Rafiei, Alberto Raggi, Fakher Rahim, Mehran Rahimi, Mahban Rahimifard, Vafa Rahimi-Movaghar, Md Obaidur Rahman, Mohammad Hifz Ur Rahman, Mosiur Rahman, Muhammad Aziz Rahman, Amir Masoud Rahmani, Mohamed Rahmani, Shayan Rahmani, Vahid Rahmanian, Premkumar Ramasubramani, Nemanja Rancic, Indu Ramachandra Rao, Sina Rashedi, Ahmed Mustafa Rashid, Nakul Ravikumar, Salman Rawaf, Elrashdy Moustafa Mohamed Redwan, Nazila Rezaei, Negar Rezaei, Nima Rezaei, Mohsen Rezaeian, Daniela Ribeiro, Mónica Rodrigues, Jefferson Antonio Buendia Rodriguez, Leonardo Roever, Esperanza Romero-Rodríguez, Aly M.A. Saad, Basema Saddik, Saeid Sadeghian, Umar Saeed, Azam Safary, Mahdi Safdarian, Sher Zaman Safi, Amene Saghazadeh, Dominic Sagoe, Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Amirhossein Sahebkar, Harihar Sahoo, Mohammad Ali Sahraian, Mirza Rizwan Sajid, Sateesh Sakhamuri, Joseph W. Sakshaug, Mohamed A. Saleh, Leili Salehi, Sana Salehi, Amir Salek Farrokhi, Sara Samadzadeh, Saad Samargandy, Noosha Samieefar, Abdallah M. Samy, Nima Sanadgol, Rama Krishna Sanjeev, Monika Sawhney, Ganesh Kumar Saya, Art Schuermans, Subramanian Senthilkumaran, Sadaf G. Sepanlou, Yashendra Sethi, Mahan Shafie, Humaira Shah, Izza Shahid, Samiah Shahid, Masood Ali Shaikh, Sadaf Sharfaei, Manoj Sharma, Maryam Shayan, Hatem Samir Shehata, Aziz Sheikh, Jeevan K. Shetty, Jae Il Shin, Reza Shirkoohi, Nebiyu Aniley Shitaye, K.M. Shivakumar, Velizar Shivarov, Parnian Shobeiri, Soraya Siabani, Migbar Mekonnen Sibhat, Emmanuel Edwar Siddig, Colin R. Simpson, Ehsan Sinaei, Harpreet Singh, Inderbir Singh, Jasvinder A. Singh, Paramdeep Singh, Surjit Singh, Md Shahjahan Siraj, Abdullah Al Mamun Sohag, Ranjan Solanki, Solikhah Solikhah, Yonatan Solomon, Mohammad Sadegh Soltani-Zangbar, Jing Sun, Mindy D. Szeto, Rafael Tabarés-Seisdedos, Seyyed Mohammad Tabatabaei, Mohammad Tabish, Ensiyeh Taheri, Azin Tahvildari, Iman M. Talaat, Jacques J.L. Lukenze Tamuzi, Ker-Kan Tan, Nathan Y. Tat, Razieh Tavakoli Oliaee, Arian Tavasol, Mohamad-Hani Temsah, Pugazhenthan Thangaraju, Samar Tharwat, Nigusie Selomon Tibebu, Jansje Henny Vera Ticoalu, Tala Tillawi, Tenaw Yimer Tiruye, Amir Tiyuri, Marcos Roberto Tovani-Palone, Manjari Tripathi, Guesh Mebrahtom Tsegay, Abdul Rohim Tualeka, Sree Sudha Ty, Chukwudi S. Ubah, Saif Ullah, Sana Ullah, Muhammad Umair, Srikanth Umakanthan, Era Upadhyay, Seyed Mohammad Vahabi, Asokan Govindaraj Vaithinathan, Sahel Valadan Tahbaz, Rohollah Valizadeh, Shoban Babu Varthya, Tommi Juhani Vasankari, Narayanaswamy Venketasubramanian, Georgios-Ioannis Verras, Jorge Hugo Villafañe, Vasily Vlassov, Danh Cao Vo, Yasir Waheed, Abdul Waris, Brhane Gebrehiwot Welegebrial, Ronny Westerman, Dakshitha Praneeth Wickramasinghe, Nuwan Darshana Wickramasinghe, Barbara Willekens, Beshada Zerfu Woldegeorgis, Melat Woldemariam, Hong Xiao, Dereje Y. Yada, Galal Yahya, Lin Yang, Fereshteh Yazdanpanah, Dong Keon Yon, Naohiro Yonemoto, Yuyi You, Mazyar Zahir, Syed Saoud Zaidi, Moein Zangiabadian, Iman Zare, Mohammad A. Zeineddine, Dawit T. Zemedikun, Naod Gebrekrstos Zeru, Chen Zhang, Hanqing Zhao, Chenwen Zhong, Magdalena Zielińska, Mohammad Zoladl, Alimuddin Zumla, Cui Guo, and Lai-shan Tam
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Immune-mediated inflammatory disease ,Incidence ,Global burden of disease study ,Trend ,Medicine (General) ,R5-920 - Abstract
Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).
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- 2023
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18. Chronotype in Patients With Immune-Mediated Inflammatory Disease: A Systematic Review.
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Butler, Thomas D., Mohammed Ali, Aala, Gibbs, Julie E., and McLaughlin, John T.
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CIRCADIAN rhythms , *MORNINGNESS-Eveningness Questionnaire , *CHRONOTYPE , *INFLAMMATORY bowel diseases , *MENTAL illness - Abstract
Immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel disease, and asthma share common pathophysiological pathways characterized by chronic inflammation and subsequent tissue damage involving multiple body sites. Circadian rhythms are 24-h body cycles that regulate immune activity and control the magnitude of immune response based on time of day. Chronotype is a person's individual circadian phase preference, ranging from morningness to eveningness, which is known to influence the risk of cardiometabolic and mental health disease. We systematically reviewed the literature to assess the association of questionnaire-based chronotype and patients with IMID. A comprehensive search of MEDLINE and Embase identified 12 studies meeting the inclusion criteria, conducted in 7 countries and covering 4 IMIDs to include 15,625 IMID patients and 410,783 healthy controls. Results showed that later chronotype may be a risk factor for worse quality of life and increased symptom burden in patients with IMIDs. In addition, chronotype may be a risk factor for IMID incidence, but the direction and magnitude of this effect were not consistent across individual IMIDs. Chronotype assessment could contribute to risk stratification in patients with IMIDs. Cross-disciplinary collaboration to understand the role of circadian rhythms and chronotype in driving common inflammatory pathways could help to improve outcomes for patients with IMIDs. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Risk of Hepatitis B Virus (HBV) Reactivation in Patients with Immune-Mediated Inflammatory Diseases Receiving Biologics: Focus on the Timing of Biologics after Anti-HBV Treatment
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Soo Min Ahn, Jonggi Choi, Byong Duk Ye, Suk-Kyun Yang, Ji Seon Oh, Yong‑Gil Kim, Chang-Keun Lee, Bin Yoo, Sang Hyoung Park, and Seokchan Hong
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hepatitis b virus ,biologics ,immune-mediated inflammatory disease ,tumor necrosis factor inhibitor ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background/Aims: Anti-hepatitis B virus (HBV) therapy is required for patients with HBV infection receiving biologics because of the high risk of HBV reactivation. However, it is unclear when to start biologics after anti-HBV treatment. We investigated the risk of HBV reactivation according to the timing of biologics initiation after anti-HBV treatment in immune-mediated inflammatory disease (IMID) patients with HBV infection. Methods: We retrospectively evaluated the incidence of HBV reactivation in IMID patients who received biologics between July 2005 and April 2020. The patients were divided into two groups (within 1-week and after 1-week) according to the timing of biologics initiation after anti-HBV treatment. The cumulative probabilities and factors associated with HBV reactivation were evaluated. Results: A total of 60 hepatitis B surface antigen-positive patients with IMID received biologics (within 1-week group, n=23 [38%]; after 1-week group, n=37 [62%]). During a median follow-up of 34 months (interquartile range, 20 to 74 months), three patients (5%) developed HBV reactivation. In univariate analysis, the timing of biologics after anti-HBV treatment was not significantly associated with the risk of HBV reactivation (hazard ratio, 0.657; 95% confidence interval, 0.059 to 7.327; p=0.733). The cumulative probabilities of HBV reactivation did not significantly differ according to the timing of biologics (p=0.731). Conclusions: The risk of HBV reactivation was not significantly associated with the timing of biologics administration after anti-HBV treatment. Thus, biologics may be initiated early in patients with IMID undergoing treatment for HBV.
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- 2022
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20. The Role of IGRA in Screening and Monitoring for TB During Anti TNF Therapy in Patients With IMID (IGRA)
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Siew Chien NG, Professor
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- 2020
21. Single-cell computational machine learning approaches to immune-mediated inflammatory disease: New tools uncover novel fibroblast and macrophage interactions driving pathogenesis.
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Fritz, Douglas, Jun Inamo, and Fan Zhang
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FIBROBLASTS ,MACHINE learning ,COMPUTATIONAL biology ,MACROPHAGES ,SYSTEMIC scleroderma - Abstract
Recent advances in single-cell sequencing technologies call for greater computational scalability and sensitivity to analytically decompose diseased tissues and expose meaningful biological relevance in individual cells with high resolution. And while fibroblasts, one of the most abundant cell types in tissues, were long thought to display relative homogeneity, recent analytical and technical advances in single-cell sequencing have exposed wide variation and sub-phenotypes of fibroblasts of potential and apparent clinical significance to inflammatory diseases. Alongside anticipated improvements in single cell spatial sequencing resolution, new computational biology techniques have formed the technical backbone when exploring fibroblast heterogeneity. More robust models are required, however. This review will summarize the key advancements in computational techniques that are being deployed to categorize fibroblast heterogeneity and their interaction with the myeloid compartments in specific biological and clinical contexts. First, typical machine-learning-aided methods such as dimensionality reduction, clustering, and trajectory inference, have exposed the role of fibroblast subpopulations in inflammatory disease pathologies. Second, these techniques, coupled with single-cell predicted computational methods have raised novel interactomes between fibroblasts and macrophages of potential clinical significance to many immune-mediated inflammatory diseases such as rheumatoid arthritis, ulcerative colitis, lupus, systemic sclerosis, and others. Third, recently developed scalable integrative methods have the potential to map cross-cell-type spatial interactions at the single-cell level while cross-tissue analysis with these models reveals shared biological mechanisms between disease contexts. Finally, these advanced computational omics approaches have the potential to be leveraged toward therapeutic strategies that target fibroblast-macrophage interactions in a wide variety of inflammatory diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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22. COVID-19 outcomes in patients with psoriasis and psoriatic arthritis: A prospective cohort study
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Di Yan, MD, Avani M. Kolla, BPhil, Trevor Young, MD, Lauren Fried, MD, Shruthi Shankar, BS, Lauren Rangel, MD, Lu Yin, MD, Rochelle Castillo, MD, Alexa Steuer, MD, Katerina Svigos, MD, Peter Izmirly, MD, Vaish Sekar, MD, Robert Lesser, MD, Gary Solomon, MD, Rebecca B. Blank, MD, Rebecca H. Haberman, MD, Andrea L. Neimann, MD, and Jose U. Scher, MD
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coronavirus ,COVID-19 ,immune-mediated inflammatory disease ,immunomodulators ,psoriasis ,psoriatic arthritis ,Dermatology ,RL1-803 - Published
- 2022
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23. Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways
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Lihe Sun, Juan Ouyang, Zhuo Zeng, Cheng Zeng, Yunqing Ma, Fang Zeng, and Shuizhu Wu
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Actively-targeting nanosystem ,Immune-mediated inflammatory disease ,Two-mode imaging ,NF-κB/NLRP3 pathways ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Biology (General) ,QH301-705.5 - Abstract
Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.
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- 2022
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24. New-Onset Rheumatic Immune-Mediated Inflammatory Diseases Following SARS-CoV-2 Vaccinations until May 2023: A Systematic Review
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Arvind Nune, Victor Durkowski, S. Sujitha Pillay, Bhupen Barman, Helen Elwell, Kaustubh Bora, Syed Bilgrami, Sajid Mahmood, Nasarulla Babajan, Srinivasan Venkatachalam, Lesley Ottewell, and Ciro Manzo
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COVID-19 vaccines ,rheumatic disease ,immune-mediated inflammatory disease ,vasculitis ,connective tissue diseases ,inflammatory arthritis ,Medicine - Abstract
A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking. Therefore, we investigated the demographics, management, and prognosis of new R-IMIDs in adults following SARS-CoV-2 vaccinations. A systematic literature search of Medline, Embase, Google Scholar, LitCovid, and Cochrane was conducted. We included any English-language study that reported new-onset R-IMID in adults following the post-COVID-19 vaccination. A total of 271 cases were reported from 39 countries between January 2021 and May 2023. The mean age of patients was 56 (range 18–90), and most were females (170, 62.5%). Most (153, 56.5%) received the Pfizer BioNTech COVID-19 vaccine. Nearly 50% of patients developed R-IMID after the second dose of the vaccine. Vasculitis was the most prevalent clinical presentation (86, 31.7%), followed by connective tissue disease (66, 24.3%). The mean duration between the vaccine’s ‘trigger’ dose and R-IMID was 11 days. Most (220, 81.2%) received corticosteroids; however, 42% (115) received DMARDs such as methotrexate, cyclophosphamide, tocilizumab, anakinra, IV immunoglobulins, plasma exchange, or rituximab. Complete remission was achieved in 75 patients (27.7%), and 137 (50.6%) improved following the treatment. Two patients died due to myositis. This SR highlights that SARS-CoV-2 vaccines may trigger R-IMID; however, further epidemiology studies are required.
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- 2023
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25. Single-cell computational machine learning approaches to immune-mediated inflammatory disease: New tools uncover novel fibroblast and macrophage interactions driving pathogenesis
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Douglas Fritz, Jun Inamo, and Fan Zhang
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computational biology ,machine learning ,single-cell omics ,spatial transcriptomics ,immune-mediated inflammatory disease ,rheumatoid arthritis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Recent advances in single-cell sequencing technologies call for greater computational scalability and sensitivity to analytically decompose diseased tissues and expose meaningful biological relevance in individual cells with high resolution. And while fibroblasts, one of the most abundant cell types in tissues, were long thought to display relative homogeneity, recent analytical and technical advances in single-cell sequencing have exposed wide variation and sub-phenotypes of fibroblasts of potential and apparent clinical significance to inflammatory diseases. Alongside anticipated improvements in single cell spatial sequencing resolution, new computational biology techniques have formed the technical backbone when exploring fibroblast heterogeneity. More robust models are required, however. This review will summarize the key advancements in computational techniques that are being deployed to categorize fibroblast heterogeneity and their interaction with the myeloid compartments in specific biological and clinical contexts. First, typical machine-learning-aided methods such as dimensionality reduction, clustering, and trajectory inference, have exposed the role of fibroblast subpopulations in inflammatory disease pathologies. Second, these techniques, coupled with single-cell predicted computational methods have raised novel interactomes between fibroblasts and macrophages of potential clinical significance to many immune-mediated inflammatory diseases such as rheumatoid arthritis, ulcerative colitis, lupus, systemic sclerosis, and others. Third, recently developed scalable integrative methods have the potential to map cross-cell-type spatial interactions at the single-cell level while cross-tissue analysis with these models reveals shared biological mechanisms between disease contexts. Finally, these advanced computational omics approaches have the potential to be leveraged toward therapeutic strategies that target fibroblast-macrophage interactions in a wide variety of inflammatory diseases.
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- 2023
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26. Global burden and cross-country inequalities in six major immune-mediated inflammatory diseases from 1990 to 2021: A systemic analysis of the Global Burden of Disease Study 2021.
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Luo H
- Abstract
Background: This study aims to describe the global burden trends of six immune-mediated inflammatory diseases (IMIDs), including asthma, atopic dermatitis (AD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA), from 1990 to 2021, and analyze patterns of cross-country inequalities., Methods: The estimates for the number of disability-adjusted life-years (DALYs) and age-standardized DALYs rates (ASDR), along with the 95 % uncertainty intervals (UI) for asthma, AD, IBD, MS, psoriasis and RA, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global burden trends of these six IMIDs from 1990 to 2021. Additionally, slope index of inequality and concentration index were employed to quantify the distributional inequalities in the burden of IMIDs., Results: From 1990 to 2021, the global ASDR of psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.25) and RA (EAPC = 0.05 %, 95 % UI: 0.01to 0.10) showed an increasing trend, while the global ASDRs of asthma (EAPC = -1.91 %, 95 % UI: -1.98 to -1.84), AD (EAPC = -0.26 %, 95 % UI: -0.27 to -0.26), IBD (EAPC = -0.52 %, 95 % UI: -0.60 to -0.43) and MS (EAPC = -0.39 %, 95 % UI: -0.45 to -0.33) demonstrated declining trends. The cross-country inequality analysis reveals pronounced heterogeneity in the burden of these six IMIDs., Conclusions: The global distribution of the DALYs burden attributable to IMIDs exhibits significant disparities across regions, underscoring an urgent need for innovative and comprehensive management strategies to address this heterogeneous landscape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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27. COVID-19 vaccination of patients with chronic immune-mediated inflammatory disease
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Yanfang, Wen, Jianfeng, Chen, Changlian, Liu, and Yan, Wang
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- 2023
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28. Inflammatory bowel disease and immune-mediated inflammatory diseases: looking at the less frequent associations.
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Bezzio, Cristina, Della Corte, Cristina, Vernero, Marta, Di Luna, Imma, Manes, Gianpiero, and Saibeni, Simone
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INFLAMMATORY bowel diseases , *EPIDERMOLYSIS bullosa , *ENDOCRINE diseases , *HIDRADENITIS suppurativa , *RESPIRATORY diseases , *TYPE 1 diabetes - Abstract
Patients with inflammatory bowel disease (IBD) often have other immune-mediated inflammatory diseases (IMIDs), and the prevalence of any IMID is higher in IBD patients than in the general population. IBD and other IMIDs involve alterations in innate and adaptive immune responses. Their co-occurrence depends on shared immune and inflammatory processes, pathogenic mechanisms, and genetic and environmental risk factors, including drugs, especially tumor necrosis factor inhibitors. The more common IMIDs associated with IBD have been widely described, so this review focuses on the less frequent associations. The IMIDs discussed here are skin disorders (psoriasis, atopic dermatitis, vitiligo, epidermolysis bullosa acquisita, cutaneous polyarteritis nodosa, and hidradenitis suppurativa), hepato-pancreatic diseases (autoimmune hepatitis, granulomatous hepatitis, and autoimmune pancreatitis), endocrine diseases (autoimmune thyroid diseases, and type 1 diabetes mellitus), multiple sclerosis, and respiratory diseases (asthma, bronchiectasis, and interstitial pneumonia). The early detection of IMIDs in IBD patients is important to prevent their deleterious clinical course and limit their psychological impact. Care for IBD patients with IMIDs should be multispecialist, with a single therapeutic strategy instead of treating each disease separately. [ABSTRACT FROM AUTHOR]
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- 2022
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29. Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare.
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Romero-Jimenez, Rosa, Escudero-Vilaplana, Vicente, Chamorro-de-Vega, Esther, Ais-Larisgoitia, Arantza, Lobato-Matilla, Elena, Somoza-Fernández, Beatriz, Ruiz-Briones, Paula, González, Carlos, Baniandrés, Ofelia, Menchén, Luis, Lobo-Rodríguez, Carmen, Herranz, Ana, and Sanjurjo, María
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MOBILE apps ,BIOTHERAPY ,MEDICAL personnel ,MOBILE health ,PATIENT autonomy - Abstract
Background: Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients. Methods: A multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app's impact on medication safety, communication, satisfaction, and usability. Results: We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10. Conclusions: We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals. [ABSTRACT FROM AUTHOR]
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- 2022
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30. Depressive symptom trajectories and polygenic risk scores in individuals with an immune-mediated inflammatory disease.
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Kowalec, Kaarina, Salter, Amber, Fitzgerald, Kathryn C., Patel, Mitulkumar, Han, Jing, Lu, Yi, Bolton, James M., Hitchon, Carol, Bernstein, Charles N., Patten, Scott, Graff, Lesley A., Marriott, James J., and Marrie, Ruth Ann
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MENTAL depression risk factors , *GENETICS , *INFLAMMATION , *REGRESSION analysis , *RISK assessment , *QUESTIONNAIRES , *ANXIETY , *IMMUNOLOGIC diseases , *BODY mass index , *ODDS ratio , *DISEASE complications - Abstract
To develop group-based trajectories of depressive symptoms in immune-mediated inflammatory disease (IMID) to understand their evolution and identify any associated factors, with the overall goal of identifying those at highest risk of higher depressive symptom burden. 922 participants had an IMID or anxiety/depression. The PHQ-9 was administered at four visits, and polygenic risk scores (PRS) for major depressive disorder, depressive symptoms, and body mass index (BMI) were generated. Group-based trajectory modelling of PHQ-9 scores estimated distinct trajectories. Regression tested whether specific factors were associated with the trajectories. Mediation analyses assessed whether IMID mediated the association between BMI PRS and trajectories. Three trajectories were identified. Regression demonstrated those in Group 3 ('high symptoms') had significantly higher PRS for the three traits, compared to Group 1 ('minimal symptoms') (OR: 1.34–1.66, P < 0.01). Stratified analyses in the IMID subgroup revealed an increased effect for BMI PRS in Group 3 (OR: 2.31, P < 0.001), in contrast, BMI PRS was no longer associated in the non-IMID sample. No significant indirect effect of BMI PRS on depressive symptoms trajectories was identified via IMID. A significant association between polygenicity and PHQ-9 trajectories supports a role for genetic inheritance in the variability in depressive symptoms in IMID. [ABSTRACT FROM AUTHOR]
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- 2022
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31. Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare
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Rosa Romero-Jimenez, Vicente Escudero-Vilaplana, Esther Chamorro-de-Vega, Arantza Ais-Larisgoitia, Elena Lobato-Matilla, Beatriz Somoza-Fernández, Paula Ruiz-Briones, Carlos González, Ofelia Baniandrés, Luis Menchén, Carmen Lobo-Rodríguez, Ana Herranz, and María Sanjurjo
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communication ,immune-mediated inflammatory disease ,mHealth ,mobile app ,monitoring ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundPharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients.MethodsA multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app’s impact on medication safety, communication, satisfaction, and usability.ResultsWe designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10.ConclusionsWe developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals.
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- 2022
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32. Safety of latent tuberculosis infection treatment in older patients with immune-mediated inflammatory diseases.
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Chung, Chiwook, Kim, Yeon Joo, Jo, Kyung-Wook, and Shim, Tae Sun
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OLDER patients , *AGE groups , *TUBERCULOSIS , *INFECTION , *MEDICAL records - Abstract
Introduction: Screening and treatment of latent tuberculosis infections (LTBI) are required before starting biologics in patients with immune-mediated inflammatory diseases (IMIDs). This study aimed to assess the safety of LTBI treatment in older patients with IMIDs. Methods: The medical records of 916 patients treated for LTBI before the start of biologics for IMIDs between January 2004 and December 2018 were reviewed. The safety profiles of LTBI treatment were retrospectively compared according to age. Results: Among the 916 patients, 201 were aged > 60 years (older age group). The older age group showed female predominance, more frequent history of previous tuberculosis, and more comorbidities, and received biologics mainly for rheumatoid arthritis. Most patients (74.0%) took isoniazid and rifampicin daily for 3 months. The treatment completion rate was 90.4% in the overall population and was lower in the older age group (91.9% vs. 85.1%, P = 0.005). Adverse drug events were more frequent in the older age group (22.9% vs. 9.8%, P < 0.001); however, differences were mainly observed for nausea (5.5% vs. 2.1%, P = 0.016) and flu-like syndrome (6.5% vs. 1.7%, P = 0.001), but not hepatotoxicity. Conclusion: LTBI treatment is generally safe in older patients with IMIDs, especially with respect to hepatotoxicity. Key points • The older age group had significantly more nausea and flu-like syndrome but not hepatotoxicity, compared to the younger age group. • LTBI treatment was acceptable and generally safe in the older age group [ABSTRACT FROM AUTHOR]
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- 2022
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33. Tyrosine kinase 2 and Janus kinase‒signal transducer and activator of transcription signaling and inhibition in plaque psoriasis.
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Krueger, James G., McInnes, Iain B., and Blauvelt, Andrew
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Plaque psoriasis is a common, chronic, systemic, immune-mediated inflammatory disease. The Janus kinase-signal transducer and activator of transcription pathway plays a major role in intracellular cytokine signaling in inflammatory processes involved in psoriasis. Although Janus kinase (JAK) 1-3 inhibitors have demonstrated efficacy in patients with moderate-to-severe psoriasis, safety concerns persist and no JAK inhibitor has received regulatory approval to treat psoriasis. Thus, an opportunity exists for novel oral therapies that are safe and efficacious in psoriasis. Tyrosine kinase 2 (TYK2) is a member of the JAK family of kinases and regulates signaling and functional responses downstream of the interleukin 12, interleukin 23, and type I interferon receptors. Deucravacitinib, which is an oral, selective inhibitor that binds to the regulatory domain of TYK2, and brepocitinib (PF-06700841) and PF-06826647, which are topical and oral TYK2 inhibitors, respectively, that bind to the active (adenosine triphosphate-binding) site in the catalytic domain, are in development for psoriasis. Selective, allosteric inhibition of TYK2 signaling may reduce the potential for toxicities associated with pan-JAK inhibitors. This article reviews Janus kinase-signal transducer and activator of transcription and TYK2 signaling and the efficacy and safety of JAK inhibitors in psoriasis to date, focusing specifically on TYK2 inhibitors. [ABSTRACT FROM AUTHOR]
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- 2022
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34. Safety of recombinant zoster vaccine: a retrospective study of 622 rheumatology patients.
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Lenfant, Tiphaine, Jin, Yuxuan, Kirchner, Elizabeth, Hajj-Ali, Rula A, Calabrese, Leonard H, and Calabrese, Cassandra
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SAFETY , *CONFIDENCE intervals , *INFLAMMATION , *TIME , *MULTIVARIATE analysis , *RETROSPECTIVE studies , *DISEASE incidence , *IMMUNOSUPPRESSION , *DOCUMENTATION , *HERPES zoster vaccines , *RHEUMATOID arthritis , *IMMUNOLOGICAL adjuvants , *HERPES zoster , *DESCRIPTIVE statistics , *SURVIVAL analysis (Biometry) , *ELECTRONIC health records , *DRUG side effects , *ODDS ratio , *RECOMBINANT proteins , *VASCULITIS , *PROPORTIONAL hazards models - Abstract
Objectives To provide insight into the safety of recombinant zoster vaccine (RZV) in patients with immune-mediated inflammatory diseases (IMID). Methods Patients who received RZV in a single-centre rheumatology department were retrospectively included. An IMID flare was defined as (i) a documentation of flare in the office notes or patient portal communication or (ii) new prednisone prescription, in the 12 weeks after each dose. Results Six-hundred and twenty-two patients were included (67% female, median age 67 years), 8.5% of them experienced adverse events (AEs) and herpes zoster (HZ) incidence was 0.6% after median follow-up of 36 weeks. Of 359 IMID patients: 88 had RA (25%), 50 vasculitis (14%) and 29 PMR (8%). At vaccination, 35% were on glucocorticoids (GC). Fifty-nine patients (16%) experienced a flare, 18 flares occurred in temporal relation to a treatment change (31%). RA patients had the highest flare rate (n = 21, 24%), 25% of patients who flared required adjustment of immunosuppression. In a multivariate analysis, use of GC at time of vaccination was associated with flare after vaccination [odds ratio (OR) 2.31 (1.3–4.1), P =0.004]. A time-to-flare survival analysis (Cox-model) showed that GC was a significant predictor of IMID flare after first RZV dose [hazard ratio (HR) 2.4 (1.3–4.5), P =0.0039] and that a flare after the first dose was associated with flaring after the second RZV dose [HR 3.9 (1.7–9), P =0.0015]. Conclusion RZV administration in patients with IMIDs was generally well-tolerated, though mild flares were not uncommon in the first 12 weeks after vaccination. These data may provide useful information for patient education when considering RZV administration. [ABSTRACT FROM AUTHOR]
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- 2021
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35. COVID-19 Outcomes in People with Rheumatic Disease: Results from a Global Physician-Reported Registry
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Izadi, Zahra
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Epidemiology ,Biostatistics ,COVID-19 ,Immune-mediated inflammatory disease ,Immunosuppressants ,real-world data ,real-world evidence ,Rheumatic disease - Abstract
The illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – a novel coronavirus identified in Wuhan at the end of 2019 that led to a global pandemic – primarily manifests as a lung infection with symptoms ranging from those of a mild upper respiratory tract infection to severe pneumonia, acute respiratory distress syndrome (ARDS), and death. Severe illness with coronavirus disease 2019 (COVID-19) can occur in healthy individuals and also in people with underlying medical conditions, including people with rheumatic diseases. Rheumatic diseases involve the dysregulation of the immune system, lead to systemic inflammation of the joints, muscles, bones, and organs, and are more prevalent in older ages.1,2 People with rheumatic disease have a higher prevalence of several comorbidities (such as pulmonary and kidney disease, heart disease or hypertension, obesity, and diabetes)3-8 and may be receiving immunosuppressive or immunomodulatory medications which can increase the risk of serious or opportunistic infections.9,10 In general, immunosuppression and the presence of comorbidities are associated with an increased risk of serious infection in people with rheumatic diseases.11 In addition, the impact of previous epidemics caused by coronavirus infections like severe acute respiratory syndrome 1 (SARS-1) and middle east respiratory syndrome (MERS) on patients with rheumatic diseases or other immune-mediated inflammatory diseases (IMIDs) has been scarcely reported.12 Therefore, in the midst of the pandemic, the implications of COVID-19 for people living with rheumatic diseases was a considerable concern. In March 2020, to address this knowledge gap, the COVID-19 Global Rheumatology Alliance (GRA) registry was developed by a global network of rheumatologists, scientists, and patient representatives.13 The GRA registry is a physician-reported registry of people with rheumatic diseases diagnosed with COVID-19 and includes information on patient demographics, rheumatic disease characteristics, immunomodulatory medications used for the treatment of rheumatic disease, and comorbidities, as well as COVID-19 diagnoses, treatments, outcomes, and complications. The overall goal of this dissertation is to use data from the GRA registry to study COVID-19 outcomes in people with rheumatic diseases to advance rheumatology care in the COVID-19 pandemic. The dissertation is organized into three chapters each describing a key aim of this dissertation. The first chapter pools data from three global COVID-19 registries of individuals with rheumatic diseases, inflammatory bowel disease (IBD), and psoriasis to compare the association between tumor necrosis factor inhibitor (TNFi) monotherapy and COVID-19-related hospitalization or death among individuals with IMIDs, with other commonly prescribed immunomodulatory regimens. Data from the pooled analysis found that TNFi monotherapy was associated with fewer hospitalizations or deaths compared with other immunomodulatory regimens including methotrexate (MTX), azathioprine/mercaptopurine (AZA/6MP), and janus kinase inhibitors (JAKi). In addition, TNFi combination therapy was associated with more favorable outcomes when MTX was used instead of AZA/6MP. These findings support the continued use of TNFi monotherapy during the pandemic and suggest that clinicians should weigh the risks versus benefits of de-escalating treatment or changing medications when a patient is receiving concomitant TNFi and AZA/6MP.The second chapter describes the development and evaluation of a prediction model for COVID-19 ARDS in people with rheumatic diseases and the development of a simple risk-score calculator for use in clinical settings. The prediction model was developed using a series of supervised machine learning algorithms and information that can be easily obtained at COVID-19 exposure or onset and predicted ARDS with good discrimination in the test set and in external validation sets. Age, daily glucocorticoid dose, pulmonary hypertension, interstitial lung disease, chronic kidney disease, anti-CD20 monoclonal antibody use, diabetes, hypertension, active rheumatic disease, and morbid obesity were identified as the most influential factors in predicting the onset of ARDS. A simple and interpretable regression-based risk-score calculator also predicted ARDS with good discrimination in the test set and in external validation sets. The risk-score calculator has the potential to guide risk-stratification and the treatment of COVID-19 among people with rheumatic diseases during the pandemic. The third chapter links data from the GRA registry to a robust array of country-level factors and uses a novel methodological approach to investigate potential mechanisms of the disparate impact of COVID-19 on people with rheumatic diseases, globally. Data from this analysis indicated that a range of factors related to geographical residence impacted COVID-19 outcomes independent of known patient-level demographic and clinical risk factors. Namely, lower country socioeconomic status, environmental exposures, higher demands on or lower capacity of health resources, and fewer government-imposed containment measures were independently associated with COVID-19-related death after controlling for patient demographics and clinical characteristics. These findings highlight the importance of environmental and societal factors as potential explanations of the observed global health disparities during the pandemic. The study designs and analytical methods utilized in this work seek to quantify and address important biases inherent to real-world conveniently sampled data. Together, findings from the three chapters provide important evidence to advance rheumatology care in the COVID-19 pandemic and lay foundation for a new research agenda to address regional disparities in COVID-19 outcomes in people with rheumatic diseases.
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- 2022
36. Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors.
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Chimalakonda, Anjaneya, Burke, James, Cheng, Lihong, Catlett, Ian, Tagen, Michael, Zhao, Qihong, Patel, Aditya, Shen, Jun, Girgis, Ihab G., Banerjee, Subhashis, and Throup, John
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PROTEIN-tyrosine kinase inhibitors , *JANUS kinases , *DRUG development , *PSORIATIC arthritis , *PROTEIN-tyrosine kinases - Abstract
Introduction: Deucravacitinib, a novel, oral, selective inhibitor of tyrosine kinase 2 (TYK2) signaling, acts via an allosteric mechanism by binding to the enzyme's regulatory domain instead of the catalytic domain. This unique binding provides high functional selectivity for TYK2 versus the closely related Janus kinases (JAKs) 1/2/3. Deucravacitinib was efficacious in phase 2 and 3 psoriasis trials, without clinical or laboratory parameters indicative of JAK 1/2/3 inhibition being observed. This analysis compared the kinase specificities of deucravacitinib versus JAK 1/2/3 inhibitors at therapeutic exposures. Methods: Signaling via JAK 1/3, JAK 2/2, and TYK2/JAK 2 dimers was measured in in vitro whole blood assays. Concentrations providing half-maximal inhibition (IC50) in these assays were determined for deucravacitinib and the JAK 1/2/3 inhibitors tofacitinib, upadacitinib, and baricitinib. Newly derived whole blood IC50 values were plotted against available pharmacokinetic profiles using doses evaluated in phase 2/3 trials. Simulated average daily inhibition and durations over which concentrations exceeded IC50 were evaluated. Results: At clinically relevant exposures, projected steady-state deucravacitinib plasma concentrations were higher than TYK2 IC50 for approximately 9–18 h. Maximal plasma concentrations (Cmax) of deucravacitinib were 8- to 17-fold lower than JAK 1/3 IC50 and > 48- to > 102-fold lower than JAK 2/2 IC50. Simulated daily average TYK2 inhibition by deucravacitinib ranged from 50% to 69%. Simulations indicated that tofacitinib, upadacitinib, and baricitinib at steady state exhibited varying degrees of JAK 1/3 (daily average inhibition, 70–94%) and JAK 2/2 (23%–67%) inhibition at therapeutic concentrations, with Cmax values 17- to 33-fold lower than their TYK2 IC50 levels. Conclusion: At clinically relevant doses and exposures, deucravacitinib demonstrates highly selective inhibition of TYK2 and not JAK 1/2/3. Tofacitinib, upadacitinib, and baricitinib variably inhibit JAK 1/2/3 but not TYK2. These results indicate that deucravacitinib is a distinct class of kinase inhibitor compared with JAK 1/2/3 inhibitors. Plain Language Summary: Psoriasis is a common, chronic inflammatory skin condition that impairs patients' physical health, emotional well-being, work performance, and overall quality of life. Psoriasis and related conditions such as psoriatic arthritis are caused by abnormalities in the immune system. Various drugs are used or explored to treat these conditions, including Janus kinase (JAK) inhibitors; however, JAK inhibitors are associated with a range of side effects such as abnormal changes in blood cell, cholesterol, and triglyceride levels, as well as liver and kidney dysfunction. Deucravacitinib is a new oral drug in development that blocks a key molecule involved in the pathogenesis of psoriasis known as tyrosine kinase 2 (TYK2). This analysis compared the selectivity of deucravacitinib versus approved JAK 1/2/3 inhibitors (tofacitinib, upadacitinib, and baricitinib) for TYK2 and JAK 1/2/3 in whole blood assays, using therapeutic doses of each drug. The authors reported that deucravacitinib inhibits TYK2 with minimal or no inhibition of JAK 1/2/3. In contrast, tofacitinib, upadacitinib, and baricitinib inhibit JAK 1, JAK 2, and/or JAK 3 to various degrees but do not inhibit TYK2. These results demonstrate that deucravacitinib is a distinct class of drug compared with the JAK 1/2/3 inhibitors. The results of this analysis are consistent with those of two recently completed phase 3 trials in patients with moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2), as well as a phase 2 trial in psoriasis, in which deucravacitinib was efficacious and well tolerated, without clinical or laboratory abnormalities suggestive of JAK 1/2/3 inhibition being observed. [ABSTRACT FROM AUTHOR]
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- 2021
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37. ImmunoStart: preparing patients for immunosuppression.
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Martin, Charlotte, Muls, Vinciane, Brasseur, Céline, Bellefon, Laurent Meric de, Hoai, Xuan-Lan Lam, Vanderhilst, Jeroen, Delforge, Marc, and Romana, Silvana Di
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INFLAMMATION treatment ,IMMUNOSUPPRESSION ,MEDICAL screening - Abstract
Objectives Patients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID. Methods Relevant information about vaccination history, tuberculosis exposure and other infectious risks were collected through blood sampling, complete anamnesis, chest X-ray and Mantoux test. During the ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations were discussed. Results Between October 2016 and February 2020, 437 patients were seen at an ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%) and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent tuberculosis infection. Conclusion This preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments. [ABSTRACT FROM AUTHOR]
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- 2021
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38. Mycobacterium tuberculosis Immune Response in Patients With Immune-Mediated Inflammatory Disease.
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Petruccioli, Elisa, Petrone, Linda, Chiacchio, Teresa, Farroni, Chiara, Cuzzi, Gilda, Navarra, Assunta, Vanini, Valentina, Massafra, Umberto, Lo Pizzo, Marianna, Guggino, Giuliana, Caccamo, Nadia, Cantini, Fabrizio, Palmieri, Fabrizio, and Goletti, Delia
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MONONUCLEAR leukocytes ,MYCOBACTERIUM tuberculosis ,RHEUMATOID arthritis ,IMMUNE response ,T cells ,CONDITIONED response - Abstract
Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB status and different risk to develop active-TB disease. We enrolled TBI subjects as example of Mtb-containment, the active-TB as example of a replicating Mtb status, and the TBI-IMID as fragile population. To study the Mtb-specific response in a condition of possible Mtb sterilization, we longitudinally enrolled TBI subjects and active-TB patients before and after TB therapy. Peripheral blood mononuclear cells were stimulated overnight with Mtb peptides contained in TB1- and TB2-tubes of the Quantiferon-Plus kit. Then, we characterized by cytometry the Mtb-specific CD4 and CD8 T cells. In TBI-IMID, the TB therapy did not affect the ability of CD4 T cells to produce interferon-γ, tumor necrosis factor-α, and interleukin-2, their functional status, and their phenotype. The TB therapy determined a contraction of the triple functional CD4 T cells of the TBI subjects and active-TB patients. The CD45RA
- CD27+ T cells stood out as a main subset of the Mtb-specific response in all groups. Before the TB-preventive therapy, the TBI subjects had higher proportion of Mtb-specific CD45RA- CD27+ CD4+ T cells and the active-TB subjects had higher proportion of Mtb-specific CD45RA- CD27- CD4+ T cells compared to other groups. The TBI-IMID patients showed a phenotype similar to TBI, suggesting that the type of IMID and the IMID therapy did not affect the activation status of Mtb-specific CD4 T cells. Future studies on a larger and better-stratified TBI-IMID population will help to understand the change of the Mtb-specific immune response over time and to identify possible immune biomarkers of Mtb-containment or active replication. [ABSTRACT FROM AUTHOR]- Published
- 2021
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39. Mycobacterium tuberculosis Immune Response in Patients With Immune-Mediated Inflammatory Disease
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Elisa Petruccioli, Linda Petrone, Teresa Chiacchio, Chiara Farroni, Gilda Cuzzi, Assunta Navarra, Valentina Vanini, Umberto Massafra, Marianna Lo Pizzo, Giuliana Guggino, Nadia Caccamo, Fabrizio Cantini, Fabrizio Palmieri, and Delia Goletti
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tuberculosis ,immune-mediated inflammatory disease ,M. tuberculosis ,IFN-γ ,CD27 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB status and different risk to develop active-TB disease. We enrolled TBI subjects as example of Mtb-containment, the active-TB as example of a replicating Mtb status, and the TBI-IMID as fragile population. To study the Mtb-specific response in a condition of possible Mtb sterilization, we longitudinally enrolled TBI subjects and active-TB patients before and after TB therapy. Peripheral blood mononuclear cells were stimulated overnight with Mtb peptides contained in TB1- and TB2-tubes of the Quantiferon-Plus kit. Then, we characterized by cytometry the Mtb-specific CD4 and CD8 T cells. In TBI-IMID, the TB therapy did not affect the ability of CD4 T cells to produce interferon-γ, tumor necrosis factor-α, and interleukin-2, their functional status, and their phenotype. The TB therapy determined a contraction of the triple functional CD4 T cells of the TBI subjects and active-TB patients. The CD45RA- CD27+ T cells stood out as a main subset of the Mtb-specific response in all groups. Before the TB-preventive therapy, the TBI subjects had higher proportion of Mtb-specific CD45RA-CD27+CD4+ T cells and the active-TB subjects had higher proportion of Mtb-specific CD45RA-CD27-CD4+ T cells compared to other groups. The TBI-IMID patients showed a phenotype similar to TBI, suggesting that the type of IMID and the IMID therapy did not affect the activation status of Mtb-specific CD4 T cells. Future studies on a larger and better-stratified TBI-IMID population will help to understand the change of the Mtb-specific immune response over time and to identify possible immune biomarkers of Mtb-containment or active replication.
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- 2021
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40. Sex-Specific Cardiovascular Comorbidities with Associations in Dermatologic and Rheumatic Disorders
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Kerkhof, Peter L. M., Khamaganova, Irina, COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, REZAEI, NIMA, Series Editor, Kerkhof, Peter L. M., editor, and Miller, Virginia M., editor
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- 2018
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41. New Immune-Mediated Inflammatory Disease Findings from Department of Rheumatology Outlined (Planned Infliximab Use During Pregnancy for Pakistani Patients With Immune-mediated Inflammatory Disease - Case Series of 12 Patients).
- Abstract
A case series of 12 pregnant women with immune-mediated inflammatory diseases (IMIDs) in Lahore, Pakistan, who were intentionally treated with infliximab, a type of anti-TNF therapy, was conducted. The study found that infliximab was effective in controlling the IMIDs during pregnancy, with 10 patients successfully completing their pregnancies without complications. The researchers concluded that the benefits of using anti-TNF therapy during pregnancy may outweigh the risks, but individual management decisions should be made after discussing the benefits and risks with the patient. This study provides valuable data on the use of infliximab during pregnancy in Pakistani patients with IMIDs. [Extracted from the article]
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- 2024
42. Researcher at Fatima Memorial Hospital Details Research in Immune-Mediated Inflammatory Disease (P017 Planned infliximab use during pregnancy for pakistani patients with immune-mediated inflammatory disease - case series of 12 patients).
- Abstract
A study conducted at Fatima Memorial Hospital in Lahore, Pakistan, focused on the use of infliximab, a medication used to treat immune-mediated inflammatory diseases (IMIDs), during pregnancy. The study included 12 pregnant women with IMIDs who were intentionally treated with infliximab. The researchers found that the use of infliximab during pregnancy was generally safe and did not increase the risk of adverse events. Most of the patients had successful pregnancies and positive outcomes. However, the researchers emphasize that the benefits and risks of using infliximab during pregnancy should be discussed with each patient individually. [Extracted from the article]
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- 2024
43. Continued JAK inhibitor treatment on the risk of recurrent herpes zoster reactivation in patients with immune-mediated inflammatory diseases: A nationwide population-based study in South Korea.
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Kim, Young-Eun, Kim, Ye-Jee, Jeong, Dae Hyun, Kim, Seonok, Kim, Min Jee, Kim, Hyeon Hwa, Jo, Kyung-Wook, Park, Sang Hyoung, and Hong, Seokchan
- Abstract
• This is the first nationwide population-based study to analyze the safety of continued use of Janus kinase (JAK) inhibitors in patients with immune-mediated inflammatory diseases (IMIDs) who develop herpes zoster (HZ) reactivation while receiving JAK inhibitor treatment. • The rate of subsequent recurrent HZ reactivation was not significantly different between patients who were maintained on JAK inhibitor treatment and those who discontinued the treatment. • In age- and sex-matched analysis, continued use of JAK inhibitor was not significantly associated with the risk of recurrent HZ reactivation (adjusted hazard ratio, 0.71; 95% CI, 0.29–1.79; P = 0.52). • JAK inhibitor treatment may be maintained in patients with IMIDs even after an event of HZ reactivation. To investigate the risk of recurrent herpes zoster (HZ) reactivation under continued Janus kinase inhibitor (JAKi) therapy in patients with immune-mediated inflammatory diseases (IMID) who developed HZ reactivation. Data from the Korean Health Insurance Review and Assessment Service (HIRA) of patients with rheumatoid arthritis (RA) or ulcerative colitis (UC) gathered from 2007 to 2021 were analyzed. A total of 3947 (RA 3540, UC 407) receiving JAKi were included. After median 0.95 years (IQR, 0.93–2.58) of therapy, 611 (15.5%) patients developed HZ reactivation (incidence rate: 8.38/100 person-years [PY]). After excluding 151 patients with lack of data after HZ reactivation, 460 patients (JAKi continuation group, n = 386 [83.9%]; JAKi discontinuation group, n = 74 [16.1%]) were analyzed for the risk of subsequent recurrent HZ reactivation. During further follow-up of median 1.11 years (IQR, 0.53–1.91), 36 (9.3%) and 6 (8.1%) patients in the JAKi continuation group and JAKi discontinuation group experienced a recurrence of HZ, respectively. The incidence rate of subsequent recurrent HZ reactivation was not significantly different between the two groups (5.3/100 vs. 5.9/100 PY; P = 0.52). After adjusting for age, sex, usage of corticosteroids, and antiviral agents, continued use of JAKi was not a significant risk factor for subsequent HZ reactivation (adjusted hazard ratio, 0.71 [CI, 0.29–1.72], P = 0.45). In this nationwide population-based study on patients with RA or UC, continued use of JAKi was not associated with a significant risk of subsequent recurrent HZ reactivation. JAKi therapy may be maintained in patients with IMID even after HZ reactivation. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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44. Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.
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Ingrasciotta, Ylenia, Spini, Andrea, L'Abbate, Luca, Fiore, Elena Sofia, Carollo, Massimo, Ientile, Valentina, Isgrò, Valentina, Cavazzana, Anna, Biasi, Valeria, Rossi, Paola, Ejlli, Lucian, Belleudi, Valeria, Poggi, Francesca, Sapigni, Ester, Puccini, Aurora, Ancona, Domenica, Stella, Paolo, Pollina Addario, Sebastiano, Allotta, Alessandra, and Leoni, Olivia
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- *
OLDER patients , *CERTOLIZUMAB pegol , *BIOLOGICALS , *CLINICAL trials , *ANKYLOSING spondylitis - Abstract
To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8–1.9) compared to RCTs (F/M ratio: 0.5–0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4–100 vs. 6–167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients. [Display omitted] • Nearly half real-world IMIDs biologics new users would not have been eligible for inclusion in the respective pivotal RCT. • Patients in real-world setting were generally older and exhibit longer follow-up compared to those from RCTs. • Post-marketing surveillance of biologics should be prioritize for patient categories excluded from RCTs. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Risk of immune-mediated inflammatory diseases in newly diagnosed ankylosing spondylitis patients: a population-based matched cohort study
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Hsin-Hua Chen, Wen-Cheng Chao, Yi-Hsing Chen, Tsu-Yi Hsieh, Kuo-Lung Lai, Yi-Ming Chen, Wei-Ting Hung, Ching-Tsai Lin, Chih-Wei Tseng, and Ching-Heng Lin
- Subjects
Ankylosing spondylitis ,Immune-mediated inflammatory disease ,Incidence ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Objective To investigate the risk of immune-mediated inflammatory diseases (IMIDs) in patients with ankylosing spondylitis (AS). Methods Using 2003–2012 claims data from the Taiwanese National Health Insurance Research Database, we identified 30,911 newly diagnosed AS patients requiring medical therapy from 2006 to 2012. In addition, we randomly selected 309,110 non-AS individuals matching (1:10) the AS patients with regard to age, sex and the year of the index date. After excluding subjects with the corresponding prior IMIDs, we calculated the incidence rates (IRs) of various IMIDs in the AS and non-AS cohorts and estimated the hazard ratios (HRs) with 95% confidence intervals after adjusting for age, sex, the Charlson comorbidity index, the frequency of ambulatory visits during the follow-up period and medications. We conducted sensitivity analyses by excluding those who developed IMIDs within 3 months after the index date. Results In the follow-up period, we found that newly diagnosed AS patients had significantly increased risks of acute anterior uveitis, psoriasis, Sjögren’s syndrome, thromboangiitis obliterans, Behcet’s disease and sarcoidosis. However, the risk of Sjögren’s syndrome did not increase in AS patients in the sensitivity analysis. In the same period, this study found no significant differences in the risks of Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, polymyositis, pemphigus and vitiligo between newly diagnosed AS patients and non-AS individuals. AS patients had a significantly reduced risk of rheumatoid arthritis. Conclusion Newly diagnosed Taiwanese AS patients had increased risks of acute anterior uveitis, psoriasis, thromboangiitis obliterans, Behcet’s disease and sarcoidosis, but a reduced risk of rheumatoid arthritis.
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- 2019
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46. Remicade® (infliximab): 20 years of contributions to science and medicine
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Melsheimer R, Geldhof A, Apaolaza I, and Schaible T
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Remicade (infliximab) ,monoclonal antibody ,immune-mediated inflammatory disease ,TNF inhibition ,Crohn’s disease ,rheumatoid arthritis ,Medicine (General) ,R5-920 - Abstract
Richard Melsheimer,1 Anja Geldhof,1 Isabel Apaolaza,1 Thomas Schaible21Medical Affairs, Janssen Biologics BV, Leiden, the Netherlands; 2Medical Affairs, Janssen Pharmaceuticals, Horsham, PA, USAAbstract: On August 24, 1998, Remicade® (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from the US Food and Drug Administration for the treatment of Crohn’s disease. Subsequently, Remicade was approved in another five adult and two pediatric indications both in the USA and across the globe. In the 20 years since this first approval, Remicade has made several important contributions to the advancement of science and medicine: 1) clinical trials with Remicade established the proof of concept that targeted therapy can be effective in immune-mediated inflammatory diseases; 2) as the first monoclonal antibody approved for use in a chronic condition, Remicade helped in identifying methods of administering large, foreign proteins repeatedly while limiting the body’s immune response to them; 3) the need to establish Remicade’s safety profile required developing new methods and setting new standards for postmarketing safety studies, specifically in the real-world setting, in terms of approach, size, and duration of follow-up; 4) the study of Remicade has improved our understanding of TNF’s role in the immune system, as well as our understanding of the pathophysiology of a range of diseases characterized by chronic inflammation; and 5) Remicade and other TNF inhibitors have transformed treatment practices in these chronic inflammatory diseases: remission has become a realistic goal of therapy and long-term disability resulting from structural damage can be prevented. This paper reviews how, over the course of its development and 20 years of use in clinical practice, Remicade was able to make these contributions.Keywords: Remicade, infliximab, monoclonal antibody, immune-mediated inflammatory disease, TNF inhibition, Crohn’s disease, rheumatoid arthritis
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- 2019
47. Brodalumab in psoriasis: evidence to date and clinical potential
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Amy C Foulkes and Richard B Warren
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immune-mediated inflammatory disease ,psoriasis ,psoriatic arthritis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Brodalumab is a recombinant, fully human monoclonal antibody (IgG2) which binds with high affinity to the interleukin (IL) 17 receptor A (IL17R). Brodalumab is now licensed and approved for the treatment of moderate-to-severe chronic plaque psoriasis in North America and Europe. As the third to market in the class of agents targeting IL-17, we review its place in the expanding armamentarium of cytokine-directed therapies for patients with severe psoriasis. Brodalumab is a highly efficacious therapy for psoriasis, whose mechanism of action is separate from other treatments targeting IL-17. Its use is associated with rapid control of the disease. We suggest that brodalumab is likely to be considered in those patients requiring rapid control of disease, where there is no known history of depression or suicidal ideation.
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- 2019
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48. A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
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Jessica D. Forbes, Chih-yu Chen, Natalie C. Knox, Ruth-Ann Marrie, Hani El-Gabalawy, Teresa de Kievit, Michelle Alfa, Charles N. Bernstein, and Gary Van Domselaar
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Gut microbiota ,Inflammatory bowel disease ,Rheumatoid arthritis ,Multiple sclerosis ,16S rRNA gene amplicon sequencing ,Immune-mediated inflammatory disease ,Microbial ecology ,QR100-130 - Abstract
Abstract Background Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach. Results Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR
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- 2018
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49. The Impact of Migration on the Gut Metagenome of South Asian Canadians
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Julia K. Copeland, Gary Chao, Shelley Vanderhout, Erica Acton, Pauline W. Wang, Eric I. Benchimol, Ahmed El-Sohemy, Ken Croitoru, Jennifer L. Gommerman, David S. Guttman, and the GEMINI Research Team
- Subjects
gut metagenome ,immune-mediated inflammatory disease ,immigration ,scfa ,prevotella ,dialister ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians.
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- 2021
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50. Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets
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Artur Wnorowski, Sylwia Wnorowska, Jacek Kurzepa, and Jolanta Parada-Turska
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metabolic network reconstruction ,G protein-coupled receptor 109B ,immune-mediated inflammatory disease ,gut inflammation ,anti-cytokine monoclonal antibodies ,nicotinamide phosphoribosyltransferase ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn’s disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.
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- 2021
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