Influenza, pneumococcal and hepatitis B vaccination in patients with rheumatic autoimmune diseases treated with immunosuppressive therapy

Patients with rheumatic autoimmune diseases have an increased risk for
morbidity and mortality due to infections. The use of immunosuppressive therapy
further increases this risk. To prevent morbidity and mortality due to
infections, patients may be vaccinated against several antigens. However,
little is known about the influence of immunosuppressive therapy on the ability
to respond to vaccinations, especially the influence of biological agents
including TNFα blocking agents, B cell depleting therapy or co-stimulation
blocking therapy.

The primary objective of this study is to evaluate the humoral response to
influenza, pneumococcal and hepatitis B vaccination in patients with rheumatic
autoimmune diseases (reumatoide artritis and poly- dermato-myositis) treated
with immunosuppressive therapy. The secondary objectives are to evaluate the
safety of these vaccinations and to evaluate the humoral response to a two-dose
vaccination regimen of influenza vaccination in patients with rheumatic
autoimmune diseases treated with immunosuppressive therapy.

This is a 28 week single centre study. Patients will receive two influenza
vaccinations at baseline and week 4, a pneumococcal vaccination at baseline and
three hepatitis B vaccinations at baseline, week 4 and week 24.
The humoral response to vaccination will be assessed at week 4 for the
influenza and pneumococcal vaccination and at week 8 for the second influenza
vaccination and at week 28 for the hepatitis B vaccinations.

Patients will receive two influenza vaccinations (Influvac, 2008-2009, Solvay
Pharma BV), one pneumococcal vaccination (Pneumovax 23, Aventis Pasteur MSD)
and three hepatitis B vaccinations (HBVAXPRO 10 microgram/ml, Sanofi Pasteur
MSD).

Patients will have six study visits in total. Patients will receive six
vaccinations: three at baseline, two at week 4 and one at week 24. Blood
samples (10 ml) to analyse the humoral responses will be taken at baseline and
at week 4, 8, 24 and 28. At baseline one blood sample (5 ml) will be taken for
hepatitis B screening. At baseline, week 4, 8, 24 and 28 blood samples (10 ml)
will be taken to assess the ESR and CRP. At each visit, except at screening,
disease activity will be assessed using the DAS28 score. The functional
disability will be assessed using a questionnaire (HAQ). Patients will receive
an adverse events registration form at each study visit to assess safety.

Participation in this study will contribute to more knowledge about the
response to vaccination in patients with rheumatic autoimmune diseases treated
with immunosuppressive therapy. The vaccinations are aimed at protection
against infections and against infectious complications. If the vaccinations in
this study are effective, the influenza vaccination will protect for one year,
the pneumococcal vaccination for about five years and the hepatitis B
vaccination for at least 20 years. Adverse events against vaccinations are not
different in patients and healthy controls. They are mostly mild and may
consist of local injection site reactions, including redness, swelling, pain,
bruising or stiffness of the arm. Sometimes, adverse events may consist of
short flu-like reactions such as fever, sweating, shivering, headache,
tiredness or muscle or joint pain. Severe allergic reactions are very rare.
Blood samples will be collected from a vein in the arm. At the injection side
bruising may occur. Other adverse events are very rare with this procedure.