Reduce Vasculitis Relapse With Immunosuppressive Drugs

Continuing azathioprine and prednisolone past 2 years from diagnosis of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis was superior to withholding the drugs with regard to relapse prevention.

Treatment with azathioprine and prednisolone for newly diagnosed ANCA-associated vasculitis should continue for at least 48 months, particularly if the patient is persistently positive for ANCA, study authors suggested.

Continuing azathioprine and prednisolone for newly diagnosed ANCA-associated vasculitis past 2 years decreases the risk of relapse by 3-fold and decreases the risk of renal failure, they concluded, noting that continuing immunosuppressive therapy for extended periods may increase the risk of malignancy and infection.

The authors pointed out that ANCA-associated vasculitis has a high relapse rate (reported in 30% to 50% of patients at 5 years) with poor predictability and that prolonged preventative therapy may itself contribute to morbidity, mortality, and organ damage. Also, end stage renal failure develops in up to 20% of patients with ANCA-associated vasculitis.

Although immunosuppressive therapy is employed for both induction and maintenance of remission, Alexandre Karras and colleagues in Europe pointed out that the optimal duration of remission maintenance therapy is currently unknown.

The authors presented the results of their randomized investigation into whether continuing azathioprine and prednisolone past 24 months reduces relapse in patients with ANCA-associated vasculitis in a recent Annals of the Rheumatic Diseases article.

The study

The authors conducted a randomized controlled study, REMAIN (prolonged REmission-MAINtenance therapy in systemic vasculitis), to look at 117 subjects with ANCA-associated vasculitis randomized to continue therapy with azathioprine and prednisolone past 24 months (n=61) or have it stopped at 24 months (n=56).

The results

• In the withdrawal group, 62.7% of the patients had a relapse, compared with 22% of subjects in the continuation group (p<0.0001).

• Relative risk of relapse was 2.84 times higher in the withdrawal group than in the continuation group (95% confidence interval, 1.72-4.9).

• Of the relapses in the withdrawal group, 78% happened after removal of the azathioprine.

• Major relapses occurred in 35.3% of withdrawal subjects and 13.5% of continuation subjects (p=0.007).

• The change in glomerular filtration rate was −3.3±14.9 mL/ min/1.73 m² in the withdrawal group and +2.5±9.8 mL/min/1.73 m² in the continuation group (p=0.01).

• End stage renal disease developed in no patients in the continuation group compared with 7.8% of the withdrawal group (p=0.012).

• By the sixth month, 72% of patients in the withdrawal group were ANCA positive compared with 52% in the continuation group (p=0.04).

• Withdrawals of immunosuppressive therapy and ANCA positivity were significant predictors of relapse (p<0.0001 and p=0.017, respectively).

• There was no statistically significant difference between groups with regard to mortality (p=0.32).

• Serious adverse events occurred in 12% of subjects; there was no difference between groups.

Implications for physicians

• Continuing immunosuppressive treatment with azathioprine and prednisolone after 24 months in patients with ANCA-associated vasculitis significantly reduces relapse.

• ANCA positivity is independently associated with relapse in ANCA-associated vasculitis.

• Continuing immunosuppressive treatment with azathioprine and prednisolone after 24 months in patients with ANCA-associated vasculitis may reduce the risk of end stage renal failure.

• Physicians should be vigilant for infections and malignancy while patients are receiving prolonged immunosuppressive therapy.

References:

Karras A, Pagnoux C, Haubitz M, et al. “Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis.” Ann Rheum Dis. 2017 Oct;76(10):1662-1668. doi: 10.1136/annrheumdis-2017-211123. Epub 2017 May 25.