Vasculitis UK News
Research study - Discontinuing Immune Suppression in ANCA Vasculitis22 Jul 2018
Balancing Drug continuation with drug withdrawal in SLE and ANCA associated vasculitis
This important research project is being run by Prof Alan Salama from the UCL Centre for Nephrology at the Royal Free Hospital and Lorraine Harper, Consultant Nephrologist at Birmingham Queen Elizabeth Hospital.
The project is exploring whether ...
- Withdrawal of immunosuppression in patients with ANCA-associated vasculitis or SLE at low risk of relapse will help reduce rates of infection and improve vaccination responses without an increase in relapse rates
- A specific immune signature can be identified in such patients and define a set of markers that could usefully stratify patients with regards need for continued immunosuppression
Background The use of immunosuppression for induction in both ANCA vasculitis and SLE is essential to prevent irreversible organ damage and death. This is followed by a period of maintenance treatment to ensure disease stabilisation. However, it remains uncertain how long treatment should be continued for and so many patients are left on long term maintenance immunosuppression.
In vasculitis a single randomised control trial of 117 patients identified that prolonged maintenance therapy beyond 24 months resulted in fewer relapses and better renal function compared with withdrawal of maintenance therapy. Adverse events were increased in the maintenance group, and overall 40% of patients developed an infection during follow-up although there was no difference in infection rates between the two groups. The only risk factors identified for relapse were azathioprine withdrawal and ANCA positivity at enrolment. None of these patients received rituximab induction therapy. However this study failed to replicate the previously identified risk factors for relapse which included pR3-ANCA positivity. In addition, the trial was not blinded meaning that physicians, knowing that the patients were not on treatment, may have had a greater tendency to interpret symptoms or signs as representing disease relapse. In a similar smaller multicentre Dutch study no difference in relapse rates was found between those patients withdrawing from therapy compared with those who were maintained on treatment. In addition the benefits of steroids beyond 6 months is also uncertain, as one single centre retrospective analysis suggested no benefit with regards disease relapse, but increased infection rates, while a meta analysis of a number of trials showed that studies where steroids were tapered off completely were associated with greater rates of relapse than those in which steroids were continued.
In SLE data are lacking, and one randomised trial has been completed and will report soon, examining the timing of MMF withdrawal.
There is therefore a great deal of uncertainty regarding maintenance treatment and this translates to a great deal of variation in how patients are managed with regards their maintenance therapy.
We believe that we can approach this safely by identifying those low risk patients (who we would currently generally propose drug withdrawal for) and randomise them to drug withdrawal or not, using placebo controls, and carefully monitoring for signs of disease recurrence. Using this group we also believe that we can study why some patients can switch their disease off and not relapse while others cannot. This could define an immune signature that could be used for other patients to help us understand if drug withdrawal would be appropriate, truly customising treatments for individuals.
There is a patient survey here