Immunogenicity and Safety of Vaccinations in Immunocompromised Persons

Arthritis, Rheumatoid Clinical Trial

Official title:

A Prospective Cohort Study in 6 Swiss Rheumatology Centres and 4 Travel Clinics on the Immunogenicity and Safety of Tetanus and Hepatitis A Vaccine in Patients With Rheumatoid Arthritis, Axial Spondyloarthritis and Vasculitis and Healthy Controls

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01947465
• Other study ID #: CS_2013_01
• Status: Completed
• Phase: N/A
• First received: August 22, 2013
• Last updated: February 24, 2016
• Start date: October 2013
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Observational

Clinical Trial 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.

Description:

The study will be placed in 6 rheumatology clinics in Switzerland and in 4 travel medicine clinics. Consecutive subjects with rheumatoid arthritis, spondylarthritis (ankylosing spondylitis), vasculitis (ANCA associated vasculitis and Behçet's disease) and healthy controls will be recruited.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 645
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Spondylarthritis
• Vasculitis

Intervention

Biological:
• Hepatitis A vaccine and tetanus vaccine
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

Locations

Country	Name	City	State
Switzerland	Cantonal Hospital Aarau, Division of Rheumatology	Aarau	Aargau
Switzerland	Swiss Tropical and Public Health Institute	Basel	Basel Town
Switzerland	University Hospital of Basel, Rheumatology Division	Basel	Basel Town
Switzerland	University of Bern, Inselspital, Division of Infectious Diseases and Travel Medicine	Bern
Switzerland	University of Bern, Inselspital, Division of Rheumatology	Bern
Switzerland	University of Geneva, University Hospitals, Division of Rheumatology	Geneva
Switzerland	University of Geneva, University Hospitals, Service de Médecine Tropicale et Humanitaire	Geneva
Switzerland	Cantonal Hospital St. Gallen, Division of Rheumatology	St. Gallen
Switzerland	University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Divison of Infectious Diseases	Zürich
Switzerland	University of Zurich, University Hopsital, Divison of Rheumatology	Zürich

Sponsors (7)

Lead Sponsor	Collaborator
University of Zurich	Cantonal Hospital of Aarau, Switzerland, Cantonal Hospital of St. Gallen, Swiss Tropical & Public Health Institute, University Hospital, Geneva, University of Basel, University of Bern

Country where clinical trial is conducted

Switzerland, 

References & Publications (8)

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. Review. — View Citation

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. Epub 2007 May 3. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

van Assen S, Elkayam O, Agmon-Levin N, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Müller-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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Safety of tetanus and hepatitis A vaccines in patients with rheumatoid arthritis, axial spondyloarthritis and vasculitis and in healthy controls	Number of patients with any worsening or reactivation of the rheumatic disease after vaccine administration; Number of participants with adverse vaccine reactions (local and systemic reactions) 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	Yes

External Links

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