Updated Vasculitis Recommendations Include New Drugs, Practices

Sara Freeman

June 02, 2022

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

Dr Bernhard Hellmich

"Until now, EGPA has usually been managed in the same way as [the] other diseases," Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

"But we now have data on each type specifically, so there is good reason to make separate recommendations," he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, "several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations," Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR's standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.

Highlights of the Changes

A key change is the introduction of four overarching principles, which weren't included in the previous update, said Hellmich.

"We moved some of the existing recommendations with low level of evidence to overarching principles," he added, stating that the first general principle was that all patients should be offered "the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs."

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.

New Recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

"We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing," Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

"We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results," Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

"Glucocorticoids are very effective, but also are the major trigger of infections in AAV," said Hellmich. This is important since infections are a major driver of early mortality in AAV.

"Another possibility to reduce glucocorticoid exposure is avacopan," he said. It's recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically "get rid of steroids."

Indeed, "for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids," Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.

Revised and Unchanged Recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

"There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice," Hellmich said.

Summing Up

"For a rare disease group, I think this is very good progress," said Hellmich, but "there are still many open questions, so we have a long research agenda."

There is purposefully no recommendation on COVID-19, however, as "the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years."

In a press release issued by the German Society for Rheumatology, which was unrelated to Hellmich's talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that "cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with."

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, "for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress."

Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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