PMC:7102591 / 15983-17705
Annnotations
LitCovid-PubTator
{"project":"LitCovid-PubTator","denotations":[{"id":"512","span":{"begin":1267,"end":1272},"obj":"Gene"},{"id":"513","span":{"begin":107,"end":115},"obj":"Species"},{"id":"514","span":{"begin":412,"end":419},"obj":"Species"},{"id":"515","span":{"begin":521,"end":529},"obj":"Species"},{"id":"516","span":{"begin":688,"end":695},"obj":"Species"},{"id":"517","span":{"begin":812,"end":820},"obj":"Species"},{"id":"518","span":{"begin":190,"end":201},"obj":"Chemical"},{"id":"519","span":{"begin":206,"end":217},"obj":"Chemical"},{"id":"520","span":{"begin":321,"end":332},"obj":"Chemical"},{"id":"521","span":{"begin":635,"end":646},"obj":"Chemical"},{"id":"522","span":{"begin":831,"end":842},"obj":"Chemical"},{"id":"523","span":{"begin":1036,"end":1046},"obj":"Chemical"},{"id":"524","span":{"begin":1294,"end":1306},"obj":"Chemical"},{"id":"525","span":{"begin":1311,"end":1321},"obj":"Chemical"},{"id":"526","span":{"begin":32,"end":56},"obj":"Disease"},{"id":"527","span":{"begin":104,"end":106},"obj":"Disease"},{"id":"528","span":{"begin":294,"end":304},"obj":"Disease"},{"id":"529","span":{"begin":518,"end":520},"obj":"Disease"}],"attributes":[{"id":"A512","pred":"tao:has_database_id","subj":"512","obj":"Gene:3716"},{"id":"A513","pred":"tao:has_database_id","subj":"513","obj":"Tax:9606"},{"id":"A514","pred":"tao:has_database_id","subj":"514","obj":"Tax:9606"},{"id":"A515","pred":"tao:has_database_id","subj":"515","obj":"Tax:9606"},{"id":"A516","pred":"tao:has_database_id","subj":"516","obj":"Tax:9606"},{"id":"A517","pred":"tao:has_database_id","subj":"517","obj":"Tax:9606"},{"id":"A518","pred":"tao:has_database_id","subj":"518","obj":"MESH:C479163"},{"id":"A519","pred":"tao:has_database_id","subj":"519","obj":"MESH:C000596027"},{"id":"A520","pred":"tao:has_database_id","subj":"520","obj":"MESH:C479163"},{"id":"A521","pred":"tao:has_database_id","subj":"521","obj":"MESH:C000596027"},{"id":"A522","pred":"tao:has_database_id","subj":"522","obj":"MESH:C479163"},{"id":"A523","pred":"tao:has_database_id","subj":"523","obj":"MESH:D011241"},{"id":"A524","pred":"tao:has_database_id","subj":"524","obj":"MESH:C000613732"},{"id":"A525","pred":"tao:has_database_id","subj":"525","obj":"MESH:C584571"},{"id":"A526","pred":"tao:has_database_id","subj":"526","obj":"MESH:D009894"},{"id":"A527","pred":"tao:has_database_id","subj":"527","obj":"MESH:D001172"},{"id":"A528","pred":"tao:has_database_id","subj":"528","obj":"MESH:D007239"},{"id":"A529","pred":"tao:has_database_id","subj":"529","obj":"MESH:D001172"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-FMA-UBERON
{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T68","span":{"begin":1598,"end":1602},"obj":"Body_part"}],"attributes":[{"id":"A68","pred":"fma_id","subj":"T68","obj":"http://purl.org/sig/ont/fma/fma68646"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-MONDO
{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T198","span":{"begin":46,"end":56},"obj":"Disease"},{"id":"T199","span":{"begin":104,"end":106},"obj":"Disease"},{"id":"T201","span":{"begin":275,"end":281},"obj":"Disease"},{"id":"T202","span":{"begin":294,"end":304},"obj":"Disease"},{"id":"T203","span":{"begin":518,"end":520},"obj":"Disease"},{"id":"T205","span":{"begin":961,"end":970},"obj":"Disease"},{"id":"T206","span":{"begin":1066,"end":1075},"obj":"Disease"},{"id":"T207","span":{"begin":1399,"end":1409},"obj":"Disease"}],"attributes":[{"id":"A198","pred":"mondo_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A199","pred":"mondo_id","subj":"T199","obj":"http://purl.obolibrary.org/obo/MONDO_0005272"},{"id":"A200","pred":"mondo_id","subj":"T199","obj":"http://purl.obolibrary.org/obo/MONDO_0008383"},{"id":"A201","pred":"mondo_id","subj":"T201","obj":"http://purl.obolibrary.org/obo/MONDO_0005609"},{"id":"A202","pred":"mondo_id","subj":"T202","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A203","pred":"mondo_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/MONDO_0005272"},{"id":"A204","pred":"mondo_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/MONDO_0008383"},{"id":"A205","pred":"mondo_id","subj":"T205","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A206","pred":"mondo_id","subj":"T206","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A207","pred":"mondo_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-CLO
{"project":"LitCovid-PD-CLO","denotations":[{"id":"T115","span":{"begin":282,"end":287},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T116","span":{"begin":556,"end":557},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T117","span":{"begin":574,"end":577},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T118","span":{"begin":1024,"end":1030},"obj":"http://purl.obolibrary.org/obo/UBERON_0003100"},{"id":"T119","span":{"begin":1197,"end":1198},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T120","span":{"begin":1211,"end":1213},"obj":"http://purl.obolibrary.org/obo/CLO_0054055"},{"id":"T121","span":{"begin":1431,"end":1432},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T122","span":{"begin":1598,"end":1602},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T123","span":{"begin":1642,"end":1651},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T124","span":{"begin":1660,"end":1685},"obj":"http://purl.obolibrary.org/obo/PR_000024990"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-CHEBI
{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T121","span":{"begin":90,"end":100},"obj":"Chemical"},{"id":"T122","span":{"begin":104,"end":106},"obj":"Chemical"},{"id":"T123","span":{"begin":190,"end":201},"obj":"Chemical"},{"id":"T124","span":{"begin":321,"end":332},"obj":"Chemical"},{"id":"T125","span":{"begin":518,"end":520},"obj":"Chemical"},{"id":"T126","span":{"begin":831,"end":842},"obj":"Chemical"},{"id":"T127","span":{"begin":1036,"end":1046},"obj":"Chemical"},{"id":"T128","span":{"begin":1283,"end":1293},"obj":"Chemical"},{"id":"T129","span":{"begin":1632,"end":1641},"obj":"Chemical"},{"id":"T130","span":{"begin":1671,"end":1673},"obj":"Chemical"}],"attributes":[{"id":"A121","pred":"chebi_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A122","pred":"chebi_id","subj":"T122","obj":"http://purl.obolibrary.org/obo/CHEBI_73810"},{"id":"A123","pred":"chebi_id","subj":"T123","obj":"http://purl.obolibrary.org/obo/CHEBI_71200"},{"id":"A124","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_71200"},{"id":"A125","pred":"chebi_id","subj":"T125","obj":"http://purl.obolibrary.org/obo/CHEBI_73810"},{"id":"A126","pred":"chebi_id","subj":"T126","obj":"http://purl.obolibrary.org/obo/CHEBI_71200"},{"id":"A127","pred":"chebi_id","subj":"T127","obj":"http://purl.obolibrary.org/obo/CHEBI_8382"},{"id":"A128","pred":"chebi_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A129","pred":"chebi_id","subj":"T129","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"},{"id":"A130","pred":"chebi_id","subj":"T130","obj":"http://purl.obolibrary.org/obo/CHEBI_74067"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-GO-BP
{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T23","span":{"begin":1598,"end":1620},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T24","span":{"begin":1598,"end":1620},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T25","span":{"begin":1642,"end":1651},"obj":"http://purl.obolibrary.org/obo/GO_0023052"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-sentences
{"project":"LitCovid-sentences","denotations":[{"id":"T86","span":{"begin":0,"end":310},"obj":"Sentence"},{"id":"T87","span":{"begin":311,"end":555},"obj":"Sentence"},{"id":"T88","span":{"begin":556,"end":707},"obj":"Sentence"},{"id":"T89","span":{"begin":708,"end":1012},"obj":"Sentence"},{"id":"T90","span":{"begin":1013,"end":1215},"obj":"Sentence"},{"id":"T91","span":{"begin":1216,"end":1463},"obj":"Sentence"},{"id":"T92","span":{"begin":1464,"end":1722},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
LitCovid-PD-HP
{"project":"LitCovid-PD-HP","denotations":[{"id":"T63","span":{"begin":32,"end":56},"obj":"Phenotype"},{"id":"T64","span":{"begin":104,"end":106},"obj":"Phenotype"},{"id":"T65","span":{"begin":518,"end":520},"obj":"Phenotype"}],"attributes":[{"id":"A63","pred":"hp_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/HP_0031690"},{"id":"A64","pred":"hp_id","subj":"T64","obj":"http://purl.obolibrary.org/obo/HP_0001370"},{"id":"A65","pred":"hp_id","subj":"T65","obj":"http://purl.obolibrary.org/obo/HP_0001370"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}
2_test
{"project":"2_test","denotations":[{"id":"32205186-31733368-4826903","span":{"begin":155,"end":157},"obj":"31733368"},{"id":"32205186-30219772-4826904","span":{"begin":703,"end":705},"obj":"30219772"},{"id":"32205186-27113415-4826905","span":{"begin":915,"end":917},"obj":"27113415"},{"id":"32205186-30183607-4826906","span":{"begin":1211,"end":1213},"obj":"30183607"},{"id":"32205186-31692920-4826907","span":{"begin":1456,"end":1458},"obj":"31692920"},{"id":"32205186-31520803-4826908","span":{"begin":1459,"end":1461},"obj":"31520803"},{"id":"32205186-28250461-4826909","span":{"begin":1718,"end":1720},"obj":"28250461"}],"text":"The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66]. Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67]. A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68]. The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70]. Older age, female sex, prednisone \u003e7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71]. More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73]. Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74]."}