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

NCT04115423 | Unknown FDA Drug

• 1 other identifier: SKKU-2019-TCZ
• Study Type: observational
• Target: 9,508
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infection; Rheumatoid Arthritis

Keywords

Tocilizumab; Serious Infection; Rheumatoid Arthritis; Tumor necrosis factor inhibitors

Outcome Measures

Primary Outcomes (1)

• Hazard ratio for serious infections

  The ratio of the hazard rates of the serious infections in tocilizumab initiators vs. TNFi users

  January 2013 to December 2018

Secondary Outcomes (1)

• Hazard ratio for six subdivided groups of serious infections by organ class

  January 2013 to December 2018

Study Arms (2)

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.

Drug: Tocilizumab

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.

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

Interventions

Tocilizumab DRUG

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

Also known as: ACTEMRA

Tocilizumab initiators

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

Also known as: ENBREL, REMICADE, HUIMIRA, and SIMPONI

Tumor necrosis factor inhibitors (TNFi) users

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who had a diagnosis of rheumatoid arthritis (ICD-10 codes: M05-06) and received tocilizumab or TNFi (etanercept, infliximab, adalimumab, and golimumab) at least once between 2013 and 2018.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Sungkyunkwan University: lead
• Ministry of Food and Drug Safety, Korea: collaborator

Study Sites (1)

Sungkyunkwan University

Suwon, Gyeonggi-do, 16419, South Korea

Location

Related Publications (10)

• 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.

  PMID: 30327685 BACKGROUND

• 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.

  PMID: 28298374 BACKGROUND

• 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.

  PMID: 27613285 BACKGROUND

• 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.

  PMID: 28282491 BACKGROUND

• 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.

  PMID: 20221663 BACKGROUND

• 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.

  PMID: 25880658 BACKGROUND

• 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.

  PMID: 30679153 BACKGROUND

• 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.

  PMID: 30612115 BACKGROUND

• 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.

  PMID: 26315675 BACKGROUND

• 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.

  PMID: 29592917 BACKGROUND

MeSH Terms

Conditions

Infections; Arthritis, Rheumatoid

Interventions

tocilizumab; Tumor Necrosis Factor Inhibitors; Etanercept; Infliximab; Adalimumab; golimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies; Antibodies, Monoclonal, Humanized

Study Officials

• Ju-Young Shin, Ph.D

  Sungkyunkwan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 4, 2019
• Study Start: April 1, 2020
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: September 10, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)