Incidence of Hospitalizations for Serious Infections in Patients Receiving Biologic Anti-Inflammatories for Rheumatologic, Psoriatic, and Gastrointestinal Conditions: A Descriptive Analysis

Purpose:

With the existing biologic anti-inflammatory product patents expiring and the FDA approval of new biosimilar and innovator biologics, patients with rheumatologic (RA), psoriatic (PsO-PsA-AS), and gastrointestinal (GI) conditions will have additional therapeutic options. This observational study will describe the patient characteristics of new users of Tumor Necrosis Factor-α (TNF) antagonists, non-TNF- α antagonists, oral DMARD, and non-biologic agents. It will describe in the treatment cohorts outcomes of serious infections that require hospitalization. The BBCIC will use the findings from this descriptive analysis to design a comparative study evaluating the real-world effectiveness and safety of biosimilar and innovator anti-inflammatory biologics.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Psoriasis; Psoriatic Arthritis; Inflammatory Bowel Disease; Ankylosing Spondylitis
• Intervention / Treatment: Drug: TNF-α antagonists, non-TNFs, DMARD non-biologics

Detailed Description

Additional information:

To most effectively interpret results from this descriptive analysis it is important to consider that this protocol was not designed to support a hypothesis. This information is being provided to the public in the interest of transparency and for demonstrating the BBCIC's Distributed Research Network's (DRN) ability to define exposures, outcomes, covariates and confounders. When published, the report will caution that the protocol does not support any ability to compare safety or effectiveness but instead is to be used only to explore the feasibility of future, more detailed comparative analyses and to better understand the capabilities of the BBCIC project. Further, the report will caution that information from this protocol should not affect use of the medical products described in any way and the fact that the BBCIC is performing this descriptive analysis in no way suggests there is a safety or effectiveness issue with any of the products described.

• Study Type: Observational
• Enrollment (Actual): 90360

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

Study subjects are selected according to inclusion criteria from a source population within the Sentinel Common Data Mode v5.0.1 (SCDM). The SCDM includes over 100 million individuals with 358 million person-years of observation time who are covered by Aetna, Anthem, Group Health Cooperative, Harvard Pilgrim Health Care, and HealthPartners. The time period assessed will be 1/1/2006 - 9/30/2015.

Description

Inclusion Criteria:

• Individuals with baseline period of 365 days with continuous medical and pharmacy coverage preceding the first prescription fill

• new and users of the following exposures

  • TNF -α antagonists (including adalimumab, certolizumab, etanercept [not included for IBD], golimumab, infliximab, and natalizumab [IBD only])
  • Non-TNF-alpha antagonist biologics in RA only (abatacept, rituximab, and tocilizumab)
  • Non-biologic medications (after any use of methotrexate in the previous year includes RA: hydroxychloroquine, leflunomide, or sulfasalazine; IBD: 6- mercaptopurine or azathioprine; PsO-PsA-AS: methotrexate, leflunomide, or sulfasalazine).

Exclusion Criteria:

• During baseline 365 days, any patient with

  • Active cancer or a history of non-melanoma cancer*
  • Any immunocompromising conditions (organ transplantation, HIV, and advanced kidney/liver disease)*
  • *if occur during the follow-up period, patients also will be censored.
• During baseline 183 days, any patient with hospitalization for any infection

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rheumatoid arthritis (RA); With exposure to TNF-α antagonists, non-TNFs, DMARD non-biologics	Drug: TNF-α antagonists, non-TNFs, DMARD non-biologics; Exposure to TNF- α antagonists, non-TNF- α antagonists, oral DMARD, or non-biologic agents.; Other Names: 18 drug names in TNF, non-TNFs, DMARD non-biologics
Inflammatory bowel disease (IBD); With exposure to TNF-α antagonists, non-TNFs, DMARD non-biologics	Drug: TNF-α antagonists, non-TNFs, DMARD non-biologics; Exposure to TNF- α antagonists, non-TNF- α antagonists, oral DMARD, or non-biologic agents.; Other Names: 18 drug names in TNF, non-TNFs, DMARD non-biologics
Psoriatic conditions; Patients with a psoriasis, psoriatic arthritis, ankylosing spondylitis with exposure to TNF-α antagonists, non-TNFs, DMARD non-biologics	Drug: TNF-α antagonists, non-TNFs, DMARD non-biologics; Exposure to TNF- α antagonists, non-TNF- α antagonists, oral DMARD, or non-biologic agents.; Other Names: 18 drug names in TNF, non-TNFs, DMARD non-biologics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hospitalization for serious infections	Primary: Incidence of hospitalization for serious infections (i.e., infections of the respiratory tract, skin and soft tissue, genito-urinary tract, gastrointestinal tract, central nervous system, septicemia/sepsis).	Anticipated completion January 2017

Collaborators and Investigators

• Sponsor: Biologics & Biosimilars Collective Intelligence Consortium
• Collaborators: Merck Sharp & Dohme LLC; Pfizer; AbbVie; University of Pittsburgh; Boehringer Ingelheim; Kaiser Permanente; Amgen; Aetna, Inc.; Harvard Pilgrim Health Care; HealthCore, Inc.; University of Alabama; Rheumatologist and Healthcare Research; Momenta Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Kevin Haynes, PharmD, MSCE, Anthem HealthCore, Inc.

Publications and helpful links

General Publications

• Mendelsohn AB, Nam YH, Marshall J, McDermott CL, Kochar B, Kappelman MD, Brown JS, Lockhart CM. Utilization patterns and characteristics of users of biologic anti-inflammatory agents in a large, US commercially insured population. Pharmacol Res Perspect. 2021 Feb;9(1):e00708. doi: 10.1002/prp2.708.

Helpful Links

• The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was established in 2015 to address anticipated needs for post-marketed evidence generation for novel biologics, their corresponding biosimilars and other related products.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: September 30, 2016
• First Posted (Estimated): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Anti-inflammatory; Biologic and Biosimilars Collective Intelligence Consortium; BBCIC; Biologics
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Infections; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Intestinal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Bone Diseases, Infectious; Ankylosis; Axial Spondyloarthritis; Arthritis; Inflammatory Bowel Diseases; Psoriasis; Arthritis, Psoriatic; Spondylitis; Spondylitis, Ankylosing; Antirheumatic Agents
• Other Study ID Numbers: BBCIC-Anti-inflammatory

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BBCIC Charter requires transparency and publication