Relapse risk not linked to plasma exchange, low-dose glucocorticoids

Relapses remain common in patients with severe AAV: Post-hoc analysis

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Undergoing plasma exchange or low-dose glucocorticoid therapy did not affect the risk of relapse in people with ANCA-associated vasculitis (AAV), according to a post-hoc analysis of data from a Phase 3 clinical trial. Post-hoc analyses are those specified and performed after a trial is complete.

Antibodies against the proteinase 3 (PR3) enzyme — one of the most common targets of AAV-driving antibodies — and respiratory symptoms were two factors associated with a significant higher risk of relapse.

These findings “continue to suggest the possibility of accurately predicting who is at risk of relapses which would provide an opportunity to tailor treatments and monitoring,” researchers wrote.

The study, “The risk of relapse of ANCA-associated vasculitis in a randomized controlled trial of plasma exchange and glucocorticoids,” was published in the journal Arthritis & Rheumatology. 

AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels, leading to problems in the kidneys and other organs. The disease is caused by self-reactive antibodies, called ANCAS, that most commonly target one of two enzymes: PR3 and myeloperoxidase (MPO).

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AAV usually treated with immunosuppressants

AAV treatment mainly consists of immunosuppressive medications to push the disease into remission. These include cyclophosphamide, rituximab (sold as Rituxan in the U.S., with available biosimilars) — used alone or combined — with or without glucocorticoids.

However, 15% of AAV patients still relapse in the first year, and 45% to 55% of patients experience a disease relapse in the first five years. Notably, the presence of anti-PR3 ANCAs have been associated with a higher relapse risk.

Plasma exchange, also called plasmapheresis, is a blood cleaning procedure that works by removing and replacing a person’s plasma, which is the liquid portion of blood that contains water, salts, and proteins such as antibodies, including ANCAs.

It “has been used to treat severe AAV with ongoing uncertainty regarding its impact on reducing the risk of kidney failure,” the researchers wrote.

A Phase 3 trial, called PEXIVAS (NCT00987389), evaluated the effectiveness of plasma exchange versus no plasma exchange and of low-dose glucocorticoid therapy versus a standard treatment regimen in 704 people with severe AAV that also affected their kidneys.

The trial’s main goal was assessing the proportion of patients experiencing kidney failure or death. Results showed neither plasma exchange nor low-dose glucocorticoids were associated with better outcomes. However, low-dose glucocorticoid treatment was linked to a reduced risk of serious infection relative to the standard dosage.

Now, researchers involved in the trial conducted a post-hoc analysis to assess the effects of plasma exchange and reduced-dose glucocorticoid therapy on the participants’ risk of relapse.

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Analysis included 649 patients who achieved remission

They analyzed data from the 649 patients (92.2%) who achieved remission over a median follow-up of three years. Remission was defined as a score of zero on the Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG). Relapse was defined as a new, worsening, or recurrence of any parameter of the BVAS/WG scale that also required a change in therapy.

The median age of the patients was 64 years, and 44.2% were women. Anti-PR3 ANCAs were detected in 41.8% of patients, and anti-MPO ANCAs in 58.2%. About half of them (50.4%) received the reduced-dose glucocorticoid therapy and the remaining 49.6% underwent plasma exchange.

A total of 147 patients (22.7%) had at least one relapse, with multiple relapses experienced by 38 patients. The majority experienced a relapse in the first year of diagnosis (68 patients), followed by 32 patients in the second year, 24 in the third year, and 16 in the fourth. Seven patients relapsed even later. In total, 204 relapses were registered.

The researchers then developed three statistical models, adjusted for different potential influencing factors, to assess the effects of either therapeutic approach on the risk of relapse.

Model one considered only variables used to stratify patients in the trial, including age, type of previous treatment, kidney function, and lung bleeding status. Model two separated two parameters of kidney problems (creatinine levels and need for dialysis) and included additional variables (sex, history of relapse, and BVAS/WG score at recruitment). Model three was similar to model two but separated disease activity according to the organs affected.

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Plasma exchange, reduced-dose glucocorticoids did not lower relapse risk

Data showed plasma exchange or reduced-dose glucocorticoid therapy did not significantly lower the risk of relapse in any of the models.

ANCAs against PR3, as well as respiratory manifestations without bleeding, were each associated with a significantly elevated risk of relapse. The relapse risk was 77% higher in PR3-associated AAV and 44% higher for patients with such respiratory symptoms.

On the contrary, dialysis at the start of the trial and use of oral cyclophosphamide as induction therapy were associated with a lower risk of relapse.

The most common relapses affected the kidneys, joints, and ears/nose/throat. About 17.7% of relapses affected an area distinct from the first disease manifestation.

“Our study provides further insight into the effects of initial treatments on the risk of relapse in AAV,” the researchers wrote. “The finding of a lack of substantial effects from [plasma exchange] and reduced-dose glucocorticoid regimens reinforces current decision making.”