Efficacy Study of Pneumococcal Vaccination in Crohn's Disease

Serological Response to Pneumococcal Vaccination in Crohn's Disease: A Prospective Multicenter Study

A growing number of patients with Crohn's disease are treated with immunosuppressive agents, such as anti-tumor necrosis factor blockers and immunomodulators. Several recent studies have indicated that immunosuppressive treatment may impair the immunological response to pneumococcal vaccination in patients with inflammatory bowel disease (Crohn's disease and Ulcerative colitis). One of weaknesses in the previous studies did not focus on specific disease, such as Crohn's disease. In addition, predictive factors affecting impaired response following pneumococcal vaccination have not clearly evaluated in patients with Crohn's disease. In this study, patients with Crohn's disease will be assessed for serological response to pneumococcal vaccination. Further, potential predictive factors that impact on vaccination outcomes and adverse events related to vaccination will be evaluated.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: 23-valent polysaccharide pneumococcal vaccine

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Kosin University Gospel Hospital
  • Cheonan, Korea, Republic of
    • Soonchunhyang University
  • Daegu, Korea, Republic of
    • Keimyung University; Dongsan Hospital
  • Iksan, Korea, Republic of
    • Wonkwang University
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of, 130-702
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Hospital
  • Seoul, Korea, Republic of
    • Chung-Ang University
  • Seoul, Korea, Republic of
    • Yonsei University; Severance Hospital
  • Seoul, Korea, Republic of
    • Ewha Womans University
  • Seoul, Korea, Republic of
    • Inje University; Seoul Paik Hospital
  • Seoul, Korea, Republic of
    • Korea University; Ansan Hospital
  • Seul, Korea, Republic of
    • Seoul National University Hospital
  • Suwon, Korea, Republic of
    • The Catholic University of Korea; St. Vincent's Hospital
  • Kangwon-do
    • Wonju, Kangwon-do, Korea, Republic of, 220-701
      • Yonsei University: Wonju Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over the age of 18
• Informed consent
• Patients who had a definitive diagnosis of Crohn's disease for more than 6 months (documented by the standard clinical, radiographic, endoscopic, and histopathologic criteria)

Exclusion Criteria:

• Hypersensitivity to any component of the pneumococcal vaccine
• Known allergy to pneumococcal vaccination
• Patients who treated with glucocorticoids (prednisolone > 20 mg/day equivalent for 2 weeks or more, and within 3 months of stopping
• Patients who inoculate another vaccine in the past 4 weeks
• Significant protein calorie malnutrition
• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, infectious, neurologic or cerebral disease
• Any condition which, in the opinion of the Investigator, places the patient at unacceptable risk if he/she were to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-TNF only; Crohn's disease, on an anti-TNF agent [infliximab or adalimumab] only	Drug: 23-valent polysaccharide pneumococcal vaccine; 23-valent polysaccharide pneumococcal vaccine (PSV-23 vaccine) 0.5mL single intramuscular injection; Other Names: Pneumovax
Experimental: Combined immunosuppression; Crohn's disease, on combined immunosuppression (both anti-TNF agent and immunomodulator [azathioprine or 6-MP])	Drug: 23-valent polysaccharide pneumococcal vaccine; 23-valent polysaccharide pneumococcal vaccine (PSV-23 vaccine) 0.5mL single intramuscular injection; Other Names: Pneumovax
Experimental: Immunomodulator only; Crohn's disease, on an immunomodulator only	Drug: 23-valent polysaccharide pneumococcal vaccine; 23-valent polysaccharide pneumococcal vaccine (PSV-23 vaccine) 0.5mL single intramuscular injection; Other Names: Pneumovax
Experimental: Non-immunosuppression; Crohn's disease, not on immunosuppressive medications (5-ASA only: control arm)	Drug: 23-valent polysaccharide pneumococcal vaccine; 23-valent polysaccharide pneumococcal vaccine (PSV-23 vaccine) 0.5mL single intramuscular injection; Other Names: Pneumovax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serological response rates	Serological response rates, defined by number of patients showing adequate response to pneumococcal vaccination (at least a 2-fold increase in antipneumococcal antibodies in the serum compared with baseline)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment of the vaccine	adverse events related to vaccine administration, including worsening of Crohn's disease activity by changes in Harvey-Bradshaw index (HBI) and inflammatory markers	8 weeks

Collaborators and Investigators

• Sponsor: Kyunghee University Medical Center
• Collaborators: Asan Medical Center; Seoul National University Hospital; Korea University; Chung-Ang University Hosptial, Chung-Ang University College of Medicine; Inje University; Ewha Womans University; The Catholic University of Korea; Severance Hospital; Keimyung University Dongsan Medical Center; Soonchunhyang University Hospital; Wonju Severance Christian Hospital; Konkuk University Hospital; Wonkwang University; Kosin University Gospel Hospital
• Investigators: Study Chair: Hyun-Soo Kim, MD, PhD, Yonsei University

Publications and helpful links

General Publications

• Melmed GY, Agarwal N, Frenck RW, Ippoliti AF, Ibanez P, Papadakis KA, Simpson P, Barolet-Garcia C, Ward J, Targan SR, Vasiliauskas EA. Immunosuppression impairs response to pneumococcal polysaccharide vaccination in patients with inflammatory bowel disease. Am J Gastroenterol. 2010 Jan;105(1):148-54. doi: 10.1038/ajg.2009.523. Epub 2009 Sep 15.
• Fiorino G, Peyrin-Biroulet L, Naccarato P, Szabo H, Sociale OR, Vetrano S, Fries W, Montanelli A, Repici A, Malesci A, Danese S. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2012 Jun;18(6):1042-7. doi: 10.1002/ibd.21800. Epub 2011 Jun 14.
• Wasan SK, Coukos JA, Farraye FA. Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists knowledge. Inflamm Bowel Dis. 2011 Dec;17(12):2536-40. doi: 10.1002/ibd.21667. Epub 2011 Apr 28.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 2, 2012
• First Submitted That Met QC Criteria: January 4, 2012
• First Posted (Estimate): January 9, 2012

Study Record Updates

• Last Update Posted (Estimate): October 16, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Crohn's disease; Pneumococcal vaccination
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: CD vaccination 1.2