CARRA Develops Consensus Treatment Plans for Severe Pediatric ANCA-Associated Vasculitis

pediatric patient examined in doctors office with parent
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans for severe pediatric ANCA-associated vasculitis to evaluate comparative effectiveness and safety.

The Childhood Arthritis and Rheumatology Research Alliance (CARRA) established consensus treatment plans for severe pediatric antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), according to a report published in Arthritis Care & Research.

Due to the rarity of pediatric AAV, randomized trials have been unfeasible and without a standardized approach to treatment. To enable the future analysis of comparative effectiveness and safety of treatment plans for severe pediatric AAV, a workgroup of CARRA members, including rheumatologists and nephrologists, formed the AAV working group to create alternative standardized treatment plans for this patient population.

The workgroup conducted a literature review of guidelines and evidence-based treatments for the management of AAV, and indicated that the target population for the consensus treatment plan was patients younger than 18 years with new-onset granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited AAV who presented with severe disease.

The workgroup provided 2 sets of dichotomous treatment alternatives for sequential treatment phases of remission-induction (cyclophosphamide or rituximab) followed by remission-maintenance (rituximab or azathioprine and methotrexate). In the latter set, azathioprine and methotrexate were considered equivalent conventional disease-modifying antirheumatic drugs compared to rituximab; these treatments were found to be concordant with the alternatives described in recent AAV treatment guidelines for adults.

Depending on the treatment guidelines for AAV, the use of cyclophosphamide vs rituximab for remission induction varied. Several guidelines have recommended the use of cyclophosphamide except when it is contraindicated or presents a risk for infertility.

Compared to azathioprine, rituximab may be preferred in remission-maintenance for the prevention of relapse; however, data suggest that secondary humoral immune suppression may be more significant in children than adults after rituximab therapy, which can lead to prolonged hypogammaglobulinemia.

“In the absence of pediatric-specific data, treatment with [rituximab] instead of [cyclophosphamide] is not yet recommended for first-line induction therapy or maintenance therapy in any current pediatric guidelines; nonetheless, [rituximab] is being increasingly used to treat [pediatric] AAV,” the workgroup noted.

Members of the workgroup indicated that they did not develop a recommendation for the use, or nonuse, of plasmapheresis or trimethoprim-sulfamethoxazole; they also added that they did not develop standardized recommendations for refractory disease or major relapse. 

However, they concluded that an increase in the use of the A Registry for Childhood Vasculitis (ARCHIVE) registry in the Pediatric Vasculitis (PedVas) initiative “would facilitate the evaluation of other emerging therapies or strategies such as high [vs] reduced dose [glucocorticoids], C5a receptor inhibitor (avacopan) as an alternative to [glucocorticoids], or early combination therapy with cyclophosphamide or rituximab, if these treatments become incorporated in adult practice guidelines.”

Disclosure: One study author has declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of the author’s disclosures.


Morishita KA, Wagner-Weiner L, Yen EY, et al; for the CARRA ANCA-Associated Vasculitis Workgroup. Consensus treatment plans for severe pediatric antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. Published online March 6, 2021. doi:10.1002/acr.24590