Prof. Bernhard Hellmich

New recommendations for the management of ANCA-associated vasculitis include for the first time use of the c5 receptor antagonist avacopan, as well as lower doses of steroids.

The consensus guidelines, which were last updated in 2016, include six new recommendations and eight revisions based on more recent findings of “several high impact studies in AAV”, rheumatologist Professor Bernhard Hellmich, Faculty of Medicine, University of Tübingen, told delegates at EULAR’s 2022 annual congress.

Tissue biopsy remains an important aspect of AAV diagnosis, but among the guidelines is a new recommendation that when there is a suspicion of AAV patients should be tested for both PR3- and MPO-ANCA using a high quality, antigen-specific assay.

This is based on “new evidence since the last update from a prospective study that the antigen specific assays have superior diagnostic accuracy” and “minimise the risk of false positives”, Prof Hellmich noted.

Also new is the recommendation that oral glucocorticoids used as part of induction regimens for remission are started at a dose of 50-75 mg of prednisolone a day (depending on body weight) followed by “a stepwise reduction” to 5mg daily by four-five months.

This advice rides on the back of clinical evidence “showing that lower glucocorticoid doses are similarly effective compared to previous standard glucocorticoid protocols, but are associated with a significantly lower rate of infections,” Prof Hellmich said.

Use of avacopan also presents a further opportunity to avoid glucocorticoid exposure, he noted. As such, the guidelines now include a recommendation for use of avacopan in combination with rituximab or cyclophosphamide to induce remission in granulomatosis with polyangiitis/microscopic polyangiitis (GPA/MPA), after a randomised controlled trial showed that the drug is at least as effective as glucocorticoids in this setting, but with less of related side effects.

EGPA spinoff

Another key difference in the 2022 guidelines is the spin-off of eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) from MPA/GPA, with four new recommendations for EGPA including: use of a combination of high-dose glucocorticoids and cyclophosphamide to induce remission of severe disease; and treatment with methotrexate, azathioprine, mepolizumab, or rituximab to maintain remission.

Key revisions to the guidelines include rituximab as the drug of choice for patients with relapsing disease, and rituximab as opposed to methotrexate for inducing remission in patients with life or organ-threatening disease, as methotrexate or mycophenolate require higher doses of glucocorticoids and new data has shown that rituximab is very effective in this patient population.

Also revised was the recommendation on how long to treat for remission maintenance; to maintain remission for GPA/MPA treatment should be continued for 24-48 months following induction of remission of new onset disease, the guidelines state.

“A longer duration of therapy should be considered in relapsing patients or those with increase risk of relapse, but should be balanced against patient preference sand risks of continuing immunosuppression”, Prof Hellmich noted.

The 2022 guidelines also include for the first time four over-arching principles, borne from three older recommendations that featured in the 2016 update but were considered to have with lower grade evidence, including that “patients with AAV should be offered best care which must be based on shared decision-making between the patients and physician considering efficacy, safety and costs,” and be “periodically screened for treatment related adverse effects and co-moribidities”.

However, no recommendations were made on COVID given that advice in the area is rapidly changing and “AAV recommendations are intended to last for years”, Prof Hellmich said.