Risk of Incident IMID in Patients Treated With Biologics and Immunosuppressive Drugs for a Single IMID (PROTECT-IMID)

Risk of Incident Immune-mediated Inflammatory Diseases (IMID) in Patients Treated With Biologics and Immunosuppressive Drugs for a Single IMID

Individuals with immune-mediated inflammatory diseases (IMIDs) are at increased risk of developing other IMIDs, possibly through shared pathogenic inflammatory pathways, and up to 25% of patients with IMIDs have at least one other IMID. Additionally, a concomitant diagnosis of a second IMID is associated with a higher burden of disease, which usually requires therapeutic escalation. Thus, this risk should be taken into account in the benefit-risk balance of IMIDs-related treatment. While the risk of other major adverse events, such as serious infection, cancer, and cardiovascular events, have been assessed in patients exposed to immunosuppressive drugs and biologics, the impact of these drugs on the risk of incident IMIDs remains largely unknown.

The main aim of this study is to assess the risk of an incident second IMID in patients starting biologics including anti-TNF and immunosuppressive drugs including small molecules for a first IMID (either inflammatory bowel disease, inflammatory rheumatic diseases, or cutaneous psoriasis).

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Disease

Detailed Description

This is a retrospective cohort study including all patients identified with a first IMID between 2008 and 2020 based on the French administrative healthcare databases (Système National des Données de Santé). Index date will be the date of initiation of the first treatment of interest within the observation period.

Primary objective

- To assess the risk of an incident second IMID in patients starting biologics including anti-TNF and immunosuppressive drugs including small molecules for a first IMID (either IBD, inflammatory rheumatic diseases, or cutaneous psoriasis)

Secondary objectives

• To describe the subtype of incident second IMIDs in patients starting biologics and immunosuppressive drugs for a first IMID and the related burden of disease.

• To assess the risk of an incident second IMID in patients starting biologics and immunosuppressive drugs for a first IMID, according to each drug class:

  • Conventional immunosuppressive drug including immunomodulators (thiopurines) and csDMARDs (methotrexate)
  • Anti-TNF (infliximab, adalimumab, golimumab, certolizumab, etanercept)
  • Biologics targeting the IL-12/IL-23 pathways (ustekinumab, risankizumab, guselkumab)
  • Biologics targeting the IL-6 pathways (tocilizumab, sarilumab)
  • Biologics targeting the IL-17 pathways (secukinumab, ixékizumab, brodalumab)
  • Biologics targeting cell adhesion, anti-integrins (vedolizumab)
  • JAK inhibitors (tofacitinib, baricitinib, upadacitinib)
• To assess the risk of an incident second IMID in patients with a first incident IMID (after January 1st, 2008) and starting biologics and immunosuppressive drugs for this IMID.

• To assess the risk of an incident second IMID in patients starting biologics and immunosuppressive drugs for a first IMID:

  • By type of first IMID
  • By type of second IMID

• Study Type: Observational
• Enrollment (Anticipated): 750000

Contacts and Locations

• Study Contact: Name: Julien KIRCHGESNER, MD, PhD; Phone Number: 33 1 49 28 31 72; Email: julien.kirchgesner@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Hopital Saint-Antoine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All the individual subtypes of second IMIDs included in the primary outcome definition, for which incidence during follow-up will be sufficient.

Description

Inclusion Criteria:

• Aged 18 years or older at index date (≥ 18 years)
• Identified with a first IMID diagnosis prior to index date, among IBD (Crohn's disease and ulcerative colitis), inflammatory rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis), or inflammatory skin diseases (psoriasis).

Exclusion Criteria:

• Patients with a diagnosis of more than one of the IMIDs of interest at index date.
• Patients exposed to biologics or immunosuppressive drugs of interest in 2006 or 2007.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients initiating a biologic or immunosuppressive drug; Patients initiating a biologic or immunosuppressive drug including small molecules for a first IMID (either IBD, inflammatory rheumatic diseases, or cutaneous psoriasis); Conventional immunosuppressive drug including immunomodulators (thiopurines) and csDMARDs (methotrexate); Anti-TNF (infliximab, adalimumab, golimumab, certolizumab, etanercept); Biologics targeting the IL-12/IL-23 pathways (ustekinumab, risankizumab, guselkumab); Biologics targeting the IL-6 pathways (tocilizumab, sarilumab); Biologics targeting the IL-17 pathways (secukinumab, ixékizumab, brodalumab); Biologics targeting cell adhesion, anti-integrins (vedolizumab); JAK inhibitors (tofacitinib, baricitinib, upadacitinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of incident second IMID	The primary outcome will be defined as the first occurrence of incident IMIDs after cohort entry, including: (Crohn's disease and ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, drug-induced lupus, sarcoidosis, vasculitis, crohn's disease and ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, drug-induced lupus, sarcoidosis, vasculitis). Identification algorithms used for inclusion criteria will be similarly used to assess outcomes. We performed a feasibility analysis by assessing the identification method of IBD diagnosis in patients previously diagnosed with either rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis. This analysis was based on a cohort of patients diagnosed with IBD between 1st January, 2008 and December 31st, 2018	between 1st January, 2008 and December 31st, 2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All the individual subtypes of second IMIDs included in the primary outcome definition	All the individual subtypes of second IMIDs included in the primary outcome definition, for which incidence during follow-up will be sufficient. Burden of disease will be based on healthcare resource utilization, notably hospitalizations, emergency department visits, outpatient visits, and drug deliveries.	between 1st January, 2008 and December 31st, 2018

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2023
• Primary Completion (Anticipated): December 15, 2023
• Study Completion (Anticipated): January 15, 2024

Study Registration Dates

• First Submitted: January 3, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: PHRC-21-0113

Drug and device information, study documents

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