Immunogenicity and Safety of Vaccinations in Immunocompromised Persons

NCT01947465 | Completed

• 1 other identifier: CS_2013_01
• Study Type: observational
• Target: 645
• Locations: 1 country
• Sites: 10

Brief Summary

Backgound and relevance of the project: Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk of contracting infections. The increased risk can be attributed to the immunological disorder itself, as well as to the immunosuppressive treatment. Vaccination against many infections is recommended in this patient group. However, the immunogenicity of vaccines may be reduced and may also be influenced by the administered treatment. Potential reactivation of the underlying disease triggered by vaccination is another important concern. From the patients' and public health perspectives, an important task of physicians is giving advice on vaccines. Completing this task is often difficult, because data on the immunogenicity and safety of vaccines in these patient groups are scarce, especially with regard to treatment with new immunosuppressive medications, such as biological agents. Lastly and importantly, due to new therapeutic options, health among AIIRD patients has considerably improved and an increasing number of patients undertake overseas travel activities requiring additional vaccinations. In this context, reliable advice with regard to vaccinations is almost impossible, because for most travel vaccinations the immunogenicity and safety profile is unknown. Research addressing the immunogenicity and safety of vaccines in different autoimmune inflammatory diseases treated with different immunosuppressive medications is urgently needed to allow giving evidence based vaccine advice. In this observational study the immunogenicity and safety of tetanus booster and hepatitis A vaccinations will be assessed in AIIRD patients. The immune response will be evaluated as a function of the underlying disease and the possible influence of commonly used immunosuppressive drugs on the immune response will be studied. Rationale for studying tetanus booster and hepatitis A vaccine Tetanus vaccination is one of the most frequently recommended vaccinations, and the effect of a booster vaccination can be addressed. Hepatitis A vaccine is the most widely used travel vaccine. Despite their importance, only very limited data are available for tetanus and hepatitis A vaccine in this patient group. By focusing on these vaccines the study will lead the way to the evaluation of further vaccines. The purpose of this study is to determine whether tetanus and hepatitis A vaccinations are as immunogenic and safe in AIIRD patients as in healthy controls.

Conditions

Arthritis, Rheumatoid; Spondylarthritis; Vasculitis

Outcome Measures

Primary Outcomes (1)

• Immunogenicity of hepatitis A and tetanus vaccination in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls

  comparison of the geometric mean antibody titre and percentage of seroprotected individuals after tetanus and hepatitis A vaccination between each disease group and healthy controls

  Change from Baseline in geometric mean antibody titre and seroprotection at 4 weeks and at 12 weeks

Secondary Outcomes (1)

• Safety of tetanus and hepatitis A vaccines in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls

  Activation of rheumatic disease will be assessed for 1 week after vaccine administration and at 4 and 12 weeks compared to baseline

Study Arms (4)

Healthy controls

If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 319 healthy controls will be enrolled and will receive hepatitis A and/or tetanus vaccination

Biological: Hepatitis A vaccine and tetanus vaccine

Patients with rheumatoid arthritis

If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with rheumatoid arthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination.

Biological: Hepatitis A vaccine and tetanus vaccine

Patients with axial spondylarthritis

If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with axial spondylarthritis will be enrolled and will receive hepatitis A and/or tetanus vaccination.

Biological: Hepatitis A vaccine and tetanus vaccine

Patients with vasculitis

If a vaccination is indicated according to the recommendations by the Swiss Federal Office of Public Health: 142 patients with vasculitis will be enrolled and will receive hepatitis A and/or tetanus vaccination.

Biological: Hepatitis A vaccine and tetanus vaccine

Interventions

Hepatitis A vaccine and tetanus vaccine BIOLOGICAL

Hepatitis A and/or tetanus vaccination will be given to participants in all group on day 0. All monovalent active hepatitis A vaccinations and all vaccines containing tetanus toxoid available in Switzerland may be used in the study

Also known as: Havrix 1440, Epaxal, Td-Pur, Boostrix, BoostrixPolio, Revaxis

Healthy controls; Patients with axial spondylarthritis; Patients with rheumatoid arthritis; Patients with vasculitis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The cohort will be selected from patients with rheumatic diseases under treatment at 6 rheumatology outpatient clinics in Switzerland (University of Basel, University of Bern, University of Geneva, University of Zurich, Cantonal Hospital Aarau, Cantonal Hospital St. Gallen)

You may qualify if:

• Indication for hepatitis A and/or tetanus vaccination according to Swiss Federal Office of Public Health recommendations
• Male and female rheumatic patients with rheumatoid arthritis or axial spondyloarthritis (ankylosing spondylitis, axial psoriatic arthritis, axial undifferentiated spondyloarthritis, enteropahtic arthritis) or peripheral psoriatic arthritis or vasculitis (Behçet's disease or ANCA-associated vasculitis) or male and female healthy participants ≥ 18 years
• Signed Informed Consent after being informed

You may not qualify if:

• Known hypersensitivity to a vaccine ingredient
• Estimated patient survival below 1 year
• Active malignant or active infectious disease
• Drug/alcohol abuse
• Insufficient understanding of local language

Sponsors & Collaborators

• University of Zurich: lead
• University of Basel: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• University of Bern: collaborator
• University Hospital, Geneva: collaborator
• Cantonal Hospital of St. Gallen: collaborator
• Cantonal Hospital of Aarau, Switzerland: collaborator

Study Sites (10)

University Hospital of Basel, Rheumatology Division

Basel, Basel Town, 4031, Switzerland

Location

Swiss Tropical and Public Health Institute

Basel, Basel Town, 4051, Switzerland

Location

Cantonal Hospital Aarau, Division of Rheumatology

Aarau, Canton of Aargau, 5001, Switzerland

Location

University of Bern, Inselspital, Division of Infectious Diseases and Travel Medicine

Bern, Canton of Bern, 3010, Switzerland

Location

University of Bern, Inselspital, Division of Rheumatology

Bern, Canton of Bern, 3010, Switzerland

Location

University of Geneva, University Hospitals, Division of Rheumatology

Geneva, Canton of Geneva, 1211, Switzerland

Location

University of Geneva, University Hospitals, Service de Médecine Tropicale et Humanitaire

Geneva, Canton of Geneva, 1211, Switzerland

Location

Cantonal Hospital St. Gallen, Division of Rheumatology

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Divison of Infectious Diseases

Zurich, Canton of Zurich, 8001, Switzerland

Location

University of Zurich, University Hopsital, Divison of Rheumatology

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (9)

• van Assen S, Elkayam O, Agmon-Levin N, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Muller-Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M. Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases. Autoimmun Rev. 2011 Apr;10(6):341-52. doi: 10.1016/j.autrev.2010.12.003. Epub 2010 Dec 20.

  PMID: 21182987 BACKGROUND

• Bijl M, Kallenberg CG, van Assen S. Vaccination of the immune-compromised patients with focus on patients with autoimmune-inflammatory diseases. Neth J Med. 2011 Jan;69(1):5-13.

  PMID: 21325695 BACKGROUND

• Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002 Sep;46(9):2287-93. doi: 10.1002/art.10524.

  PMID: 12355475 BACKGROUND

• Bernatsky S, Hudson M, Suissa S. Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. Rheumatology (Oxford). 2007 Jul;46(7):1157-60. doi: 10.1093/rheumatology/kem076. Epub 2007 May 3.

  PMID: 17478469 BACKGROUND

• Kotton CN. Vaccination and immunization against travel-related diseases in immunocompromised hosts. Expert Rev Vaccines. 2008 Jul;7(5):663-72. doi: 10.1586/14760584.7.5.663.

  PMID: 18564020 BACKGROUND

• Rahier JF, Moutschen M, Van Gompel A, Van Ranst M, Louis E, Segaert S, Masson P, De Keyser F. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford). 2010 Oct;49(10):1815-27. doi: 10.1093/rheumatology/keq183. Epub 2010 Jun 29.

  PMID: 20591834 BACKGROUND

• Steffen R, Kane MA, Shapiro CN, Billo N, Schoellhorn KJ, van Damme P. Epidemiology and prevention of hepatitis A in travelers. JAMA. 1994 Sep 21;272(11):885-9.

  PMID: 8078167 BACKGROUND

• Agarwal N, Ollington K, Kaneshiro M, Frenck R, Melmed GY. Are immunosuppressive medications associated with decreased responses to routine immunizations? A systematic review. Vaccine. 2012 Feb 14;30(8):1413-24. doi: 10.1016/j.vaccine.2011.11.109. Epub 2011 Dec 21.

  PMID: 22197580 BACKGROUND

• Buhler S, Jaeger VK, Adler S, Bannert B, Brummerhoff C, Ciurea A, Distler O, Franz J, Gabay C, Hagenbuch N, Herzog C, Hasler P, Kling K, Kyburz D, Muller R, Nissen MJ, Siegrist CA, Villiger PM, Walker UA, Hatz C. Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study. Rheumatology (Oxford). 2019 Sep 1;58(9):1585-1596. doi: 10.1093/rheumatology/kez045.

  PMID: 30877773 DERIVED

Related Links

• Vaccination recommendations in immunocompromised travelers by the Centers for Disease Control and Prevention
• Vaccination recommendations in immunocompromised persons, Belgium
• Vaccination recommendation for patients with rheumatic disease, Swiss society of rheumatology

Biospecimen

Retention: SAMPLES WITHOUT DNA

Sera from participants will be kept in a biobank for further measurements of antibody responses after vaccination.

MeSH Terms

Conditions

Arthritis, Rheumatoid; Spondylarthritis; Vasculitis

Interventions

Hepatitis A Vaccines; Tetanus Toxoid; epaxal berna; Boostrix

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylitis; Spinal Diseases; Bone Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Toxoids

Study Officials

• Christoph Hatz, Professor

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2013
• First Posted: September 20, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: February 25, 2016

Record last verified: 2016-02

Locations

CH (10)