A Retrospective Cohort Study on the Risk of Serious Infections in Rheumatoid Arthritis Patients Receiving Tocilizumab

NCT ID: NCT04115423

Last Updated: 2020-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

9508 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-04-01

Study Completion Date

2021-10-01

Brief Summary

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The purpose of this study is to evaluate whether the risk of serious infections in rheumatoid arthritis patients with tocilizumab is higher than in those with tumor necrosis factor inhibitors using the nationwide real-world data.

Detailed Description

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This observational, retrospective cohort study using the Korean National Health Insurance (NHI) data will evaluate whether the risk of serious infections (SIs) in rheumatoid arthritis patients treated with tocilizumab is higher than in those with tumor necrosis factor inhibitors. We will compare incidence rates between two groups and estimate relative risks of SIs in tocilizumab users using the time-dependent Cox proportional hazard regression. Various covariates potentially related to RA severity and occurrence of infection will be assessed and used for adjustment.

Conditions

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Infection Rheumatoid Arthritis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Tocilizumab initiators

Patients over 18 years of age with a diagnosis of RA (ICD-10 codes: M05-06) and receiving tocilizumab at least once from January 2013 to December 2018. Tocilizumab initiators are required to have no record of tocilizumab within 1 year prior to the first prescription of tocilizumab.

Tocilizumab

Intervention Type DRUG

A humanized monoclonal antibody against the interleukin-6 receptor, which is mainly for the treatment of rheumatoid arthritis.

Tumor necrosis factor inhibitors (TNFi) users

Patients over 18 years of age with a diagnosis of RA (ICD-10 codes: M05-06) and receiving TNFi at least once from January 2013 to December 2018. TNFi users will be patients who had no record of tocilizumab and given specific TNFi during 1 year before the first prescription of TNFi.

Tumor Necrosis Factor Inhibitor (etanercept, infliximab, adalimumab, and golimumab)

Intervention Type DRUG

Tumor Necrosis Factor inhibitors (TNFi) are a group of medicines that suppresses the physiologic response to TNF, a protein involved in early inflammatory events. We will include etanercept, infliximab, adalimumab, and golimumab as TNFis since these drugs are commercialized in Korea.

Interventions

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Tocilizumab

A humanized monoclonal antibody against the interleukin-6 receptor, which is mainly for the treatment of rheumatoid arthritis.

Intervention Type DRUG

Tumor Necrosis Factor Inhibitor (etanercept, infliximab, adalimumab, and golimumab)

Tumor Necrosis Factor inhibitors (TNFi) are a group of medicines that suppresses the physiologic response to TNF, a protein involved in early inflammatory events. We will include etanercept, infliximab, adalimumab, and golimumab as TNFis since these drugs are commercialized in Korea.

Intervention Type DRUG

Other Intervention Names

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ACTEMRA ENBREL, REMICADE, HUIMIRA, and SIMPONI

Eligibility Criteria

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Inclusion Criteria

* Individuals who had a diagnosis of rheumatoid arthritis (ICD-10 codes: M05-06) between 2013 and 2018

Exclusion Criteria

* Individuals less than 18 years of age
* Having no records of prescription of tocilizumab or TNFi at least once between 2013 and 2018
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Food and Drug Safety, Korea

OTHER_GOV

Sponsor Role collaborator

Sungkyunkwan University

OTHER

Sponsor Role lead

Responsible Party

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Ju-Young Shin

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ju-Young Shin, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Sungkyunkwan University

Locations

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Sungkyunkwan University

Suwon, Gyeonggi-do, South Korea

Site Status

Countries

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South Korea

References

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Jones G, Panova E. New insights and long-term safety of tocilizumab in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018 Oct 7;10(10):195-199. doi: 10.1177/1759720X18798462. eCollection 2018 Oct.

Reference Type BACKGROUND
PMID: 30327685 (View on PubMed)

Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, Bijlsma JW, Burmester GR, Scholte-Voshaar M, Falzon L, Landewe RBM. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017 Jun;76(6):1101-1136. doi: 10.1136/annrheumdis-2016-210708. Epub 2017 Mar 15.

Reference Type BACKGROUND
PMID: 28298374 (View on PubMed)

Singh JA. Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a Scoping Review of Serious or Hospitalized Infections in Observational Studies. Curr Rheumatol Rep. 2016 Oct;18(10):61. doi: 10.1007/s11926-016-0609-5.

Reference Type BACKGROUND
PMID: 27613285 (View on PubMed)

Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, Maxwell LJ, Buchbinder R, Lopez-Olivo MA, Suarez-Almazor ME, Tugwell P, Wells GA. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017 Mar 10;3(3):CD012591. doi: 10.1002/14651858.CD012591.

Reference Type BACKGROUND
PMID: 28282491 (View on PubMed)

Nishimoto N, Ito K, Takagi N. Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions. Mod Rheumatol. 2010 Jun;20(3):222-32. doi: 10.1007/s10165-010-0279-5. Epub 2010 Mar 11.

Reference Type BACKGROUND
PMID: 20221663 (View on PubMed)

Sakai R, Cho SK, Nanki T, Watanabe K, Yamazaki H, Tanaka M, Koike R, Tanaka Y, Saito K, Hirata S, Amano K, Nagasawa H, Sumida T, Hayashi T, Sugihara T, Dobashi H, Yasuda S, Sawada T, Ezawa K, Ueda A, Fujii T, Migita K, Miyasaka N, Harigai M; REAL Study Group. Head-to-head comparison of the safety of tocilizumab and tumor necrosis factor inhibitors in rheumatoid arthritis patients (RA) in clinical practice: results from the registry of Japanese RA patients on biologics for long-term safety (REAL) registry. Arthritis Res Ther. 2015 Mar 23;17(1):74. doi: 10.1186/s13075-015-0583-8.

Reference Type BACKGROUND
PMID: 25880658 (View on PubMed)

Pawar A, Desai RJ, Solomon DH, Santiago Ortiz AJ, Gale S, Bao M, Sarsour K, Schneeweiss S, Kim SC. Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study. Ann Rheum Dis. 2019 Apr;78(4):456-464. doi: 10.1136/annrheumdis-2018-214367. Epub 2019 Jan 24.

Reference Type BACKGROUND
PMID: 30679153 (View on PubMed)

Gron KL, Arkema EV, Glintborg B, Mehnert F, Ostergaard M, Dreyer L, Norgaard M, Krogh NS, Askling J, Hetland ML; ARTIS Study Group. Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden. Ann Rheum Dis. 2019 Mar;78(3):320-327. doi: 10.1136/annrheumdis-2018-214326. Epub 2019 Jan 5.

Reference Type BACKGROUND
PMID: 30612115 (View on PubMed)

Yun H, Xie F, Delzell E, Levitan EB, Chen L, Lewis JD, Saag KG, Beukelman T, Winthrop KL, Baddley JW, Curtis JR. Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. Arthritis Rheumatol. 2016 Jan;68(1):56-66. doi: 10.1002/art.39399.

Reference Type BACKGROUND
PMID: 26315675 (View on PubMed)

Rutherford AI, Subesinghe S, Hyrich KL, Galloway JB. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018 Jun;77(6):905-910. doi: 10.1136/annrheumdis-2017-212825. Epub 2018 Mar 28.

Reference Type BACKGROUND
PMID: 29592917 (View on PubMed)

Other Identifiers

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SKKU-2019-TCZ

Identifier Type: -

Identifier Source: org_study_id

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