Investigating the drug mycophenolate mofetil for the treatment of polyarteritis nodosa (PAN) in children

Disease - Polyarteritis nodosa

Lead applicant - Professor Paul Brogan

Organisation - University College London

Type of grant - Clinical Studies

Status of grant - Active

Amount of the original award - £77,471.64

Start date - 1 July 2013

Reference - 20094

Public Summary

What are the aims of this research?

The aim of this clinical study is to investigate the effectiveness and safety of the drug mycophenolate mofetil (MMF) compared to the current standard cyclophosphamide (CYC) for treatment of polyarteritis nodosa (PAN), a serious inflammatory blood vessel disease, in children. This study will compare the effectiveness and safety of the two treatments in children with PAN.

Why is this research important?

PAN is a form of vasculitis that results from an autoimmune process attacking the blood vessels. It is the third commonest form of vasculitis encountered in childhood and symptoms include fever, arthritis, skin rash, and abdominal pain. Current treatment for this condition is a combination of steroids and CYC, which has been established practice for over 30 years. However CYC is not licensed for this purpose, and there has never been a clinical trial for PAN in children. With this treatment, mortality rates for PAN are currently between 3 and 10%, however there are concerns regarding unacceptably high levels of side-effects related to the use of CYC in children. 25 to 50% will experience serious side effects which may include significant nausea and vomiting, bladder toxicity, severe bleeding and hair loss. CYC is also associated with an increased risk of infertility and cancer. There is therefore a need for clinical trials of alternative drugs to replace CYC.

MMF is a newer drug which is attractive due to its oral administration (which is better for children) and also as it is believed to be a safer therapeutic option. MMF has been used to successfully treat childhood PAN for the last 10 years, and MMF is equally effective as CYC in treating systemic lupus erythematosus. This, combined with years of experience using MMF to prevent rejection after organ transplantation, including in children, suggests that MMF is a safer alternative. However, this needs to be confirmed in a proper trial.

How will the findings benefit patients?

This is the first ever randomised controlled trial for PAN in children, and could lead to significant reduction in side effects related to treatment. The results of this trial therefore would be of immediate and direct clinical benefit for children with PAN.