Predicting Hospitalized Infection in Patients With Chronic Inflammatory Arthritis Treated With Biological Drugs

Development of a Prediction Model for the Risk of Hospitalized Infection in Patients With Chronic Inflammatory Arthritis Treated With Biological Drugs

Background The risk for hospitalized infection (i.e. infection leading to hospitalization) in patients with inflammatory arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) treated with biological drugs is known to be increased compared to the background population. In daily clinical practice, there is a need for a simple way to assess the absolute risk for hospitalized infection in individual patients based on easily available information such as age, diagnosis, functional status, comorbidities and medication. This risk estimate will be useful in clinical decision making e.g. when advising patients on whether or not to initiate biologic therapy or when advising patients on influenza or pneumococcal vaccination.

Objectives The objectives are 1) to assess the risk for hospitalized infection (infection leading to hospitalization) in patients with inflammatory arthritis during 12 months of follow-up after initiating treatment with their first biological drug (bDMARD) with the risk in the general population, and 2) to develop a simple, clinically useful algorithm that allows prediction of the risk of hospitalized infection in individual patients.

Methods Observational cohort study based on existing data in: The Danish Rheumatology Register (DANBIO), The Danish National Patient Register, The Danish National Prescription Register and The Danish Register of Causes of Death. All patients registered in DANBIO with RA, PsA or axSpA who initiated treatment with their first biological drug between January 1, 2006 and December 31, 2016 will be identified. Baseline predictors and outcomes (hospitalized infection or death) during 12 months of follow-up are obtained. Logistic regression analysis and 10-fold cross-validation will be used to develop and internally validate the prediction model.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Psoriatic Arthritis; Spondyloarthritis
• Intervention / Treatment: Drug: Biologic Agents

• Study Type: Observational
• Enrollment (Anticipated): 7500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

For each cohort, a set of matched controls from the general population will be obtained, so that outcomes in each diagnosis group can be compared with its own matched controls. Therefore, 3 groups of matched controls are constructed. Ten controls from the general population will be drawn for each patient matched by age, sex and postal code (replacement is allowed). Index date equal to date of start of first bDMARD. At the index date, controls must not have or have had one the diagnoses of RA, SpA or PsA listed above. Baseline variables (predictors) and outcomes (for definitions and details, see below) will be collected in the same time periods for each individual patient and his/her 10 matched controls.

Description

Inclusion criteria:

• Patients with RA: Registered in DANBIO with a diagnosis of M05.9, M06.0 or M06.9.
• Patients with SpA: Registered in DANBIO with a diagnosis of M45.9, M46.1, M46.8+M02.9, M46.8+M07.4, M46.8+M07.5 or M46.9.
• Patients with PsA: Registered in DANBIO with a diagnosis of M07.3 or M46.8+M07.2.
• First bDMARD treatment course.
• Start of treatment with first bDMARD in the period January 1, 2006 to December 31, 2016.
• Age at start of treatment with first bDMARD ≥ 18 years.

Exclusion criteria:

- Not followed in DANBIO since start of first bDMARD.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rheumatoid Arthritis; Registered in DANBIO with a diagnosis of M05.9, M06.0 or M06.9.	Drug: Biologic Agents; Other Names: Rituximab; Etanercept; Adalimumab; Tocilizumab; Anakinra; Secukinumab; Abatacept; Infliximab; Ustekinumab; Certolizumab; Golimumab
Spondyloarthritis; Registered in DANBIO with a diagnosis of M45.9, M46.1, M46.8+M02.9, M46.8+M07.4, M46.8+M07.5 or M46.9.	Drug: Biologic Agents; Other Names: Rituximab; Etanercept; Adalimumab; Tocilizumab; Anakinra; Secukinumab; Abatacept; Infliximab; Ustekinumab; Certolizumab; Golimumab
Psoriatic Arthritis; Registered in DANBIO with a diagnosis of M07.3 or M46.8+M07.2.	Drug: Biologic Agents; Other Names: Rituximab; Etanercept; Adalimumab; Tocilizumab; Anakinra; Secukinumab; Abatacept; Infliximab; Ustekinumab; Certolizumab; Golimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalized infection or death	Hospitalization caused by infection or death	12 months of follow-up

Collaborators and Investigators

• Sponsor: Simon Krabbe
• Collaborators: Zealand University Hospital; University of Aarhus; University of Southern Denmark
• Investigators: Study Chair: Merete L Hetland, DMSc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2006
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): December 31, 2017

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: April 5, 2018
• First Posted (ACTUAL): April 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 12, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Infection; Hospitalization
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Arthritis; Infections; Arthritis, Psoriatic; Spondylitis; Spondylarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Immune Checkpoint Inhibitors; Tumor Necrosis Factor Inhibitors; Etanercept; Adalimumab; Infliximab; Golimumab; Abatacept; Ustekinumab
• Other Study ID Numbers: Predict-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No