To assess the effect of adalimumab and rituximab on the safety and efficacy of vaccination with T cell-dependent and T cell-independent primary and recall antigens.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Ancillary infectious topics
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of patients with positive response to vaccination prior and post
adalimumab or rituximab therapy, and measured 4 weeks after administration of
the vaccins. Response is defined as a 2-fold increase in antibody levels to the
administered antigens or as an absolute change in specific antibody of 1 g/mL,
or seroconversion in patients with a non-protective baseline level of
antibodies (<1/40).
Secondary outcome
To analyse the effect of RA disease parameters on vaccination and the influence
of adalimumab and rituximab therapy on T and B cell response after vaccination
as well as the relation T-B cell response.This will be done by analyzing T and
B cell subsets, T cell cytokine production to specific antibody stimulus as
measured by elispot and immunoglobuline subtypes.
Background summary
Infection is one of the leading causes of morbidity and mortality in patients
with rheumatoid arthritis. Immunomodulating therapies may potentiate the
already-increased tendency of these patients to develop serious infectious
complications. As vaccination is one of the primary strategy to reduce the
morbidity and mortality, several rheumatogists therefore suggest implementing
vaccination in RA patients treated with anti -TNF.
Little is known about the effects of vaccination in patients with rheumatoid
arthritis, and upto now, no data are available on patients with RA who are
treated with adalinumab (anti TNFalpha) or rituximab (anti B cell) therapy.
In general there are 2 main vaccine catagories: T cell independent vaccines
(conjugate vaccines) and T cell independent (polysaccharide) vaccines. In this
study, we want to gain insight in the response of the immune system on T cell
dependent and independent vaccines while being treated with anti-TNF alpha and
after B cell depletion.
Study objective
To assess the effect of adalimumab and rituximab on the safety and efficacy of
vaccination with T cell-dependent and T cell-independent primary and recall
antigens.
Study design
This is a randomised patient control cross-over study.
All patients eligible for treatment with adalimumab or rituximab wil be asked
to participate in this vaccination trial. To correct for a possible influence
of one of the vaccines on the response to the other vaccines, patients will be
randomised to 2 different vaccination schedules. One set of vaccines consists
of a T cell-dependent primary antigen (KLH) combined with a T cell-independent
antigen against pneumococci (Pneumovax®) and the Tetanus Toxoid recall antigen.
The other set of vaccines consists of the T cell-dependent primary antigen
against hepatitis A combined with the T cell-independent primary antigen
against meningococci (Meningovax A+C®) and the polio recall antigen. Four weeks
after the first immunization, adalimumab or rituximab treatment is initiated.
Six weeks after the start of adalimumab treatment rituximab treatment, patients
cross-over to vaccination with the other set of vaccines.
Intervention
All patients will receive 2 sets of vaccines. The first set 4 weeks prior the
initiation of anti-TNFalpha or Rituximab therapy, the second set 6 weeks after
initiation of the therapy.
Study burden and risks
During the course of the study (16 weeks) all patients will receive 2 sets of
vaccines, each consisting one T cell dependent, one T cell independent and one
recall antigen
There are no reasons to beleive the side-effects of this vaccination for the
participants differ from vaccination of healthy volonteers.
Allergic reactions have been described after administration of each of the
vaccins seperately. Local skin rash and painfull injection site are relatively
common (1-10%). More severe or prolonged reactions are rare. They include fever
(0.1%) and seizures (0.01%).
Next to the administration of the vaccines, all patients will visit the
hospital 7 times and a total of 300 ml of blood will be drawn.
meibergdreef 9
1105 AZ Amsterdam Zuidoost
NL
meibergdreef 9
1105 AZ Amsterdam Zuidoost
NL
Listed location countries
Age
Inclusion criteria
- RA diagnosed according to the revised 1987 criteria of the American College of Rheumatology (ACR) for at least 3 months
- Age 18-85 years
-Eligible for anti-TNF * or Rituximab therapy (according to the Dutch guidelines)
Exclusion criteria
- Pregnancy
- Breastfeeding
- Therapy within the previous 60 days with:
*any experimental drug
*alkylating agents, e.g. cyclophosphamide, chlorambucil
*monoclonal antibodies (including infliximab and etanercept)
*growth factors
*other cytokines
- A positive PPD skin test (> 4 mm induration)
- HIV infection
- History of severe allergic or anaphylactic reactions to vaccines
- Vaccination with KLH, Pneumovax, Meningovax, Polio or tetanus toxoid in the past 12 months
- Fever (orally measured > 38 °C), chronic infections or infections requiring anti-microbial therapy
- Manifest cardiac failure (stage III or IV according to NYHA classification)
- Progressive fatal disease/terminal illness
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005666-39-NL |
| CCMO | NL14888.018.06 |