Treatment of severe gout patients with rasburicase

Gout is the most prevalent inflammatory rheumatic disease. Treatment of gout in
primary care, as well as in a hospital setting is often suboptimal. Adherence
to therapy is generally poor and treatment is often limited to acute attacks
rather than adequately treating gout with urateFurthermore, even a substantial
number of patients on urate lowering therapy cannot reach serum urate target
due to intolerance, lack of effect, or co-morbidity limiting treatment options.
This often results in severe, disabling disease. Recombinant uricases have been
shown to have a very strong urate lowering potential.

The primary outcome parameter is the Gout Activity Score (GAS)after 6 months of
rasburicase treatment. Secondary outcome parameters are the serum uric acid
concentration, the clinical evaluation of tophus load, patient reported
outcomes: MD-HAQ, GAQ and safety measures (number of AE/SAEs), anti-drug
antibody titers and to investigate B-cells response against Rasbirucase.

The study design is a proof of concept clinical pilot study in 20 patients with
severe, tophaceous gout. All included patients will be treated with rasbirucase
infusion for six months, with an additional follow up three months after last
infusion or after discontinuation. Visits are scheduled monthly for infusion
with Rasbirucase.

All 20 included patients will be treated with monthly infusion of rasburicase,
0.20mg/kg intravenously for 6 months. To prevent infusion
reactions/anaphylaxis, patients will receive 5mg levocetirizine po 2 hours
before infusion and 100mg methylprednisolone iv concomitantly. In case of an
infusion reaction or anaphylaxis, or a severe adverse event, treatment will be
discontinued. There will be an observational follow-up period of 3 months after
the last infusion.

The burden for participants will consist of the monthly infusion of rasburicase
with pre-medication and associated diagnostic tests
described in the section *Methods*. Despite administration of pre-medication
and intensive monitoring of the participants at the day
treatment facility a risk of infusion reaction or anaphylaxis to rasburicase
exists. In previous investigations these have not been
reported to be severe. However, before each administration anti-rasburicase
antibodies as well as rasburicase trough level will be
determined. In case of high antibody titers and unmeasurable rasburicase trough
level, rasburicase administration will be
discontinued for safety reasons to prevent an infusion reaction or anaphylaxis.
In addition, there is a risk of (serious) adverse events
or side effects to rasburicase. Finally, participants have an increased risk
for gout flares, particularly in the 6 months period of
monthly rasburicase administration, in spite of co-administration of
methylprednisolone.