Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation
Aim To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients. Methods RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic dis...
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| Veröffentlicht in: | International journal of rheumatic diseases 2017-07, Vol.20 (7), p.859-869 |
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| creator | Chen, Le‐Feng Mo, Ying‐Qian Jing, Jun Ma, Jian‐Da Zheng, Dong‐Hui Dai, Lie |
| description | Aim
To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.
Methods
RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. Liver function and HBV infection status were evaluated at baseline, weeks 4, 8 and 12.
Results
Sixty‐three RA patients who were qualified for statistics were classified as chronic HBV infection (n = 7), resolved HBV infection (n = 41) and non‐HBV infection (n = 15). Three patients with chronic HBV infection and without antiviral prophylaxis developed HBV reactivation after 1–3 doses of TCZ. They were asymptomatic of hepatitis B with normal aminotransferases and the HBV‐DNA of three patients with HBV reactivation became undetectable after therapeutic antiviral therapy. No HBV reactivation developed in patients with resolved HBV infection. Aminotransferases elevated in 22% of all patients, but became elevated ≥ 2‐fold of normal range in only two patients: one was treated with adefovir before TCZ for active hepatitis B and the other had resolved HBV infection, with aminotransferases returning to normal 4 weeks later. Thirty‐two patients with resolved HBV infection had positive anti‐HBs (≥ 10 IU/L) which is a protective antibody. The anti‐HBs titer reduced significantly at week 4 and week 8 after the first dose of TCZ compared to baseline (P < 0.05) and even reduced to negative in six (19%). The anti‐HBs did not return to positive in three patients during follow‐up of 12–36 weeks.
Conclusions
This prospective clinical observation preliminarily indicated three‐dose TCZ combined with csDMARDs might increase the risk of HBV reactivation in RA patients with chronic HBV infection, but in this study patients remained asymptomatic and had a benign outcome after antiviral treatment. To identify the exact risk of TCZ on HBV infection and the prognosis of TCZ‐related HBV reactivation, further studies with larger sample sizes and fewer confounding factors are needed. |
| doi_str_mv | 10.1111/1756-185X.13010 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1865539341</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1922338900</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3710-61ba065f3ccd825005aa0f8f9cd490e1d905b81ca8583074413a7670f6c3b2393</originalsourceid><addsrcrecordid>eNqFkc9u1DAQxi1ERduFMzdkiQuXbcdx7DjcSsU_aaUiARI3y3Emiks2XmynVTnxCL3wgjwJTlP20Au-2Jr5fZ9m_BHynMEJy-eUVUKumRLfThgHBo_I0b7yeP8u2SE5jvESQDIuqyfksFBMQlnII_L7c-9D-vPr1vopRKTJWze4n9PWNNSNNqCJGGlw8Tv1He1xZ5JLLtI39MqFKXfQ2OSuctWPWUDnPo4p0muXehp6zE7Ju5aakPowS19TQ3fBxx3OQqR2cKOzZqC-iRgWp6fkoDNDxGf394p8fff2y_mH9ebi_cfzs83a8orBWrLGgBQdt7ZVhQAQxkCnutq2ZQ3I2hpEo5g1SigOVVkybipZQSctbwpe8xV5tfjmgX5MGJPeumhxGMyIfoqaKSlE5rJwRV4-QC_zj415Os3qouBc1QCZOl0omzeMATu9C25rwo1moOfE9JyJnvPRd4llxYt736nZYrvn_0WUAbEA127Am__56bNPm8X4L8gto-0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1922338900</pqid></control><display><type>article</type><title>Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Chen, Le‐Feng ; Mo, Ying‐Qian ; Jing, Jun ; Ma, Jian‐Da ; Zheng, Dong‐Hui ; Dai, Lie</creator><creatorcontrib>Chen, Le‐Feng ; Mo, Ying‐Qian ; Jing, Jun ; Ma, Jian‐Da ; Zheng, Dong‐Hui ; Dai, Lie</creatorcontrib><description>Aim
To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.
Methods
RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. Liver function and HBV infection status were evaluated at baseline, weeks 4, 8 and 12.
Results
Sixty‐three RA patients who were qualified for statistics were classified as chronic HBV infection (n = 7), resolved HBV infection (n = 41) and non‐HBV infection (n = 15). Three patients with chronic HBV infection and without antiviral prophylaxis developed HBV reactivation after 1–3 doses of TCZ. They were asymptomatic of hepatitis B with normal aminotransferases and the HBV‐DNA of three patients with HBV reactivation became undetectable after therapeutic antiviral therapy. No HBV reactivation developed in patients with resolved HBV infection. Aminotransferases elevated in 22% of all patients, but became elevated ≥ 2‐fold of normal range in only two patients: one was treated with adefovir before TCZ for active hepatitis B and the other had resolved HBV infection, with aminotransferases returning to normal 4 weeks later. Thirty‐two patients with resolved HBV infection had positive anti‐HBs (≥ 10 IU/L) which is a protective antibody. The anti‐HBs titer reduced significantly at week 4 and week 8 after the first dose of TCZ compared to baseline (P < 0.05) and even reduced to negative in six (19%). The anti‐HBs did not return to positive in three patients during follow‐up of 12–36 weeks.
Conclusions
This prospective clinical observation preliminarily indicated three‐dose TCZ combined with csDMARDs might increase the risk of HBV reactivation in RA patients with chronic HBV infection, but in this study patients remained asymptomatic and had a benign outcome after antiviral treatment. To identify the exact risk of TCZ on HBV infection and the prognosis of TCZ‐related HBV reactivation, further studies with larger sample sizes and fewer confounding factors are needed.</description><identifier>ISSN: 1756-1841</identifier><identifier>EISSN: 1756-185X</identifier><identifier>DOI: 10.1111/1756-185X.13010</identifier><identifier>PMID: 28160426</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adefovir ; Administration, Intravenous ; Adult ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antibodies, Monoclonal, Humanized - adverse effects ; Antirheumatic Agents - administration & dosage ; Antirheumatic Agents - adverse effects ; Antiviral agents ; Arthritis, Rheumatoid - diagnosis ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - immunology ; Benign ; Biomarkers - blood ; Chronic infection ; Deoxyribonucleic acid ; DNA ; DNA, Viral - genetics ; Drug Administration Schedule ; Female ; Health risk assessment ; Hepatitis ; Hepatitis B ; Hepatitis B Antibodies - blood ; hepatitis B virus ; Hepatitis B virus - genetics ; Hepatitis B virus - immunology ; Hepatitis B virus - pathogenicity ; Humans ; Immunocompromised Host ; Immunosuppressive agents ; Infections ; Intravenous administration ; Liver ; Liver Function Tests ; Male ; Middle Aged ; Monoclonal antibodies ; Prognosis ; Prophylaxis ; Prospective Studies ; reactivation ; Rheumatoid arthritis ; Risk Factors ; Time Factors ; tocilizumab ; Treatment Outcome ; Viral Load ; Virus Activation</subject><ispartof>International journal of rheumatic diseases, 2017-07, Vol.20 (7), p.859-869</ispartof><rights>2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd</rights><rights>2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.</rights><rights>International Journal of Rheumatic Diseases © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3710-61ba065f3ccd825005aa0f8f9cd490e1d905b81ca8583074413a7670f6c3b2393</citedby><cites>FETCH-LOGICAL-c3710-61ba065f3ccd825005aa0f8f9cd490e1d905b81ca8583074413a7670f6c3b2393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1756-185X.13010$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1756-185X.13010$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28160426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Le‐Feng</creatorcontrib><creatorcontrib>Mo, Ying‐Qian</creatorcontrib><creatorcontrib>Jing, Jun</creatorcontrib><creatorcontrib>Ma, Jian‐Da</creatorcontrib><creatorcontrib>Zheng, Dong‐Hui</creatorcontrib><creatorcontrib>Dai, Lie</creatorcontrib><title>Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation</title><title>International journal of rheumatic diseases</title><addtitle>Int J Rheum Dis</addtitle><description>Aim
To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.
Methods
RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. Liver function and HBV infection status were evaluated at baseline, weeks 4, 8 and 12.
Results
Sixty‐three RA patients who were qualified for statistics were classified as chronic HBV infection (n = 7), resolved HBV infection (n = 41) and non‐HBV infection (n = 15). Three patients with chronic HBV infection and without antiviral prophylaxis developed HBV reactivation after 1–3 doses of TCZ. They were asymptomatic of hepatitis B with normal aminotransferases and the HBV‐DNA of three patients with HBV reactivation became undetectable after therapeutic antiviral therapy. No HBV reactivation developed in patients with resolved HBV infection. Aminotransferases elevated in 22% of all patients, but became elevated ≥ 2‐fold of normal range in only two patients: one was treated with adefovir before TCZ for active hepatitis B and the other had resolved HBV infection, with aminotransferases returning to normal 4 weeks later. Thirty‐two patients with resolved HBV infection had positive anti‐HBs (≥ 10 IU/L) which is a protective antibody. The anti‐HBs titer reduced significantly at week 4 and week 8 after the first dose of TCZ compared to baseline (P < 0.05) and even reduced to negative in six (19%). The anti‐HBs did not return to positive in three patients during follow‐up of 12–36 weeks.
Conclusions
This prospective clinical observation preliminarily indicated three‐dose TCZ combined with csDMARDs might increase the risk of HBV reactivation in RA patients with chronic HBV infection, but in this study patients remained asymptomatic and had a benign outcome after antiviral treatment. To identify the exact risk of TCZ on HBV infection and the prognosis of TCZ‐related HBV reactivation, further studies with larger sample sizes and fewer confounding factors are needed.</description><subject>Adefovir</subject><subject>Administration, Intravenous</subject><subject>Adult</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized - adverse effects</subject><subject>Antirheumatic Agents - administration & dosage</subject><subject>Antirheumatic Agents - adverse effects</subject><subject>Antiviral agents</subject><subject>Arthritis, Rheumatoid - diagnosis</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Benign</subject><subject>Biomarkers - blood</subject><subject>Chronic infection</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Viral - genetics</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B Antibodies - blood</subject><subject>hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B virus - pathogenicity</subject><subject>Humans</subject><subject>Immunocompromised Host</subject><subject>Immunosuppressive agents</subject><subject>Infections</subject><subject>Intravenous administration</subject><subject>Liver</subject><subject>Liver Function Tests</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Prognosis</subject><subject>Prophylaxis</subject><subject>Prospective Studies</subject><subject>reactivation</subject><subject>Rheumatoid arthritis</subject><subject>Risk Factors</subject><subject>Time Factors</subject><subject>tocilizumab</subject><subject>Treatment Outcome</subject><subject>Viral Load</subject><subject>Virus Activation</subject><issn>1756-1841</issn><issn>1756-185X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi1ERduFMzdkiQuXbcdx7DjcSsU_aaUiARI3y3Emiks2XmynVTnxCL3wgjwJTlP20Au-2Jr5fZ9m_BHynMEJy-eUVUKumRLfThgHBo_I0b7yeP8u2SE5jvESQDIuqyfksFBMQlnII_L7c-9D-vPr1vopRKTJWze4n9PWNNSNNqCJGGlw8Tv1He1xZ5JLLtI39MqFKXfQ2OSuctWPWUDnPo4p0muXehp6zE7Ju5aakPowS19TQ3fBxx3OQqR2cKOzZqC-iRgWp6fkoDNDxGf394p8fff2y_mH9ebi_cfzs83a8orBWrLGgBQdt7ZVhQAQxkCnutq2ZQ3I2hpEo5g1SigOVVkybipZQSctbwpe8xV5tfjmgX5MGJPeumhxGMyIfoqaKSlE5rJwRV4-QC_zj415Os3qouBc1QCZOl0omzeMATu9C25rwo1moOfE9JyJnvPRd4llxYt736nZYrvn_0WUAbEA127Am__56bNPm8X4L8gto-0</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Chen, Le‐Feng</creator><creator>Mo, Ying‐Qian</creator><creator>Jing, Jun</creator><creator>Ma, Jian‐Da</creator><creator>Zheng, Dong‐Hui</creator><creator>Dai, Lie</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201707</creationdate><title>Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation</title><author>Chen, Le‐Feng ; Mo, Ying‐Qian ; Jing, Jun ; Ma, Jian‐Da ; Zheng, Dong‐Hui ; Dai, Lie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3710-61ba065f3ccd825005aa0f8f9cd490e1d905b81ca8583074413a7670f6c3b2393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adefovir</topic><topic>Administration, Intravenous</topic><topic>Adult</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized - adverse effects</topic><topic>Antirheumatic Agents - administration & dosage</topic><topic>Antirheumatic Agents - adverse effects</topic><topic>Antiviral agents</topic><topic>Arthritis, Rheumatoid - diagnosis</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Benign</topic><topic>Biomarkers - blood</topic><topic>Chronic infection</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Viral - genetics</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B Antibodies - blood</topic><topic>hepatitis B virus</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B virus - pathogenicity</topic><topic>Humans</topic><topic>Immunocompromised Host</topic><topic>Immunosuppressive agents</topic><topic>Infections</topic><topic>Intravenous administration</topic><topic>Liver</topic><topic>Liver Function Tests</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Prognosis</topic><topic>Prophylaxis</topic><topic>Prospective Studies</topic><topic>reactivation</topic><topic>Rheumatoid arthritis</topic><topic>Risk Factors</topic><topic>Time Factors</topic><topic>tocilizumab</topic><topic>Treatment Outcome</topic><topic>Viral Load</topic><topic>Virus Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Le‐Feng</creatorcontrib><creatorcontrib>Mo, Ying‐Qian</creatorcontrib><creatorcontrib>Jing, Jun</creatorcontrib><creatorcontrib>Ma, Jian‐Da</creatorcontrib><creatorcontrib>Zheng, Dong‐Hui</creatorcontrib><creatorcontrib>Dai, Lie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Le‐Feng</au><au>Mo, Ying‐Qian</au><au>Jing, Jun</au><au>Ma, Jian‐Da</au><au>Zheng, Dong‐Hui</au><au>Dai, Lie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation</atitle><jtitle>International journal of rheumatic diseases</jtitle><addtitle>Int J Rheum Dis</addtitle><date>2017-07</date><risdate>2017</risdate><volume>20</volume><issue>7</issue><spage>859</spage><epage>869</epage><pages>859-869</pages><issn>1756-1841</issn><eissn>1756-185X</eissn><abstract>Aim
To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.
Methods
RA patients with moderate to high disease activity, with at least one feature of poor prognosis and inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. Liver function and HBV infection status were evaluated at baseline, weeks 4, 8 and 12.
Results
Sixty‐three RA patients who were qualified for statistics were classified as chronic HBV infection (n = 7), resolved HBV infection (n = 41) and non‐HBV infection (n = 15). Three patients with chronic HBV infection and without antiviral prophylaxis developed HBV reactivation after 1–3 doses of TCZ. They were asymptomatic of hepatitis B with normal aminotransferases and the HBV‐DNA of three patients with HBV reactivation became undetectable after therapeutic antiviral therapy. No HBV reactivation developed in patients with resolved HBV infection. Aminotransferases elevated in 22% of all patients, but became elevated ≥ 2‐fold of normal range in only two patients: one was treated with adefovir before TCZ for active hepatitis B and the other had resolved HBV infection, with aminotransferases returning to normal 4 weeks later. Thirty‐two patients with resolved HBV infection had positive anti‐HBs (≥ 10 IU/L) which is a protective antibody. The anti‐HBs titer reduced significantly at week 4 and week 8 after the first dose of TCZ compared to baseline (P < 0.05) and even reduced to negative in six (19%). The anti‐HBs did not return to positive in three patients during follow‐up of 12–36 weeks.
Conclusions
This prospective clinical observation preliminarily indicated three‐dose TCZ combined with csDMARDs might increase the risk of HBV reactivation in RA patients with chronic HBV infection, but in this study patients remained asymptomatic and had a benign outcome after antiviral treatment. To identify the exact risk of TCZ on HBV infection and the prognosis of TCZ‐related HBV reactivation, further studies with larger sample sizes and fewer confounding factors are needed.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28160426</pmid><doi>10.1111/1756-185X.13010</doi><tpages>11</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adefovir Administration, Intravenous Adult Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - adverse effects Antirheumatic Agents - administration & dosage Antirheumatic Agents - adverse effects Antiviral agents Arthritis, Rheumatoid - diagnosis Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - immunology Benign Biomarkers - blood Chronic infection Deoxyribonucleic acid DNA DNA, Viral - genetics Drug Administration Schedule Female Health risk assessment Hepatitis Hepatitis B Hepatitis B Antibodies - blood hepatitis B virus Hepatitis B virus - genetics Hepatitis B virus - immunology Hepatitis B virus - pathogenicity Humans Immunocompromised Host Immunosuppressive agents Infections Intravenous administration Liver Liver Function Tests Male Middle Aged Monoclonal antibodies Prognosis Prophylaxis Prospective Studies reactivation Rheumatoid arthritis Risk Factors Time Factors tocilizumab Treatment Outcome Viral Load Virus Activation |
| title | Short‐course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation |
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