Alliance Sets Treatment Plans by Consensus for Severe Pediatric AAV
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) has established alternative consensus treatment plans for children and adolescents with severe ANCA-associated vasculitis (AAV).
These plans, which compare two therapies for induction and maintenance of remission in pediatric AAV patients, were generally accepted by practicing physicians who regularly work with these patients and who will help gather more data and create better guidelines.
“The ultimate goal of this initiative has been to provide a more standardized treatment framework to enable more systematic outcome evaluation of children with AAV,” the researchers wrote.
The report, “Consensus Treatment Plans for Severe Pediatric Antineutrophil Cytoplasmic Antibody‐Associated Vasculitis,” was published in Arthritis Care & Research.
AAV is a group of diseases characterized by inflammation in small blood vessels that causes damage to multiple organs and tissues.
The disease is more common in adults, but it can occur in children and adolescents. Yet, the rarity of AAV in younger patients has limited the development of clinical practice recommendations, leaving specialists to adapt adult guidelines to pediatric patients.
To improve the care of these young patients, CARRA set out to develop consensus treatment plans for severe pediatric AAV that will enable the comparative evaluation of two therapies for each treatment setting when randomized clinical trials are not feasible.
Essentially, after reviewing existing data, experts in AAV treatment were asked to vote on the two most appropriate therapies for induction and maintenance. Finalized plans would then be disseminated to physicians who were asked to treat their patients with the selected approaches only.
As patient data is entered into a registry, researchers can gather enough data to compare the two approaches in the future.
“Our approach was not to develop comprehensive pediatric evidence-based guidance, but [to] select from current pediatric practice two commonly used treatment alternatives … that align with the adult evidence-based guidelines,” the research team wrote.
The CARRA-AAV working group included pediatric rheumatologists and nephrologists who reviewed published studies and management guidelines for children and adolescents newly diagnosed with severe AAV. The disease subtypes included in the analyses were granulomatosis with polyangiitis, microscopic polyangiitis, or AAV limited to the kidneys.
After several meetings, surveys, and email discussions, the group established one consensus treatment plan for remission-induction and one for remission-maintenance. Both plans had a consensus of at least 80% of the experts.
In the remission-induction plan, rituximab and intravenous (into-the-vein) cyclophosphamide were included as primary treatment alternatives, with 100% consensus.
The alternatives selected for the remission-maintenance plan were azathioprine or methotrexate against rituximab, also selected with 100% consensus.
Glucocorticoids were included in the remission-induction plan with 91% consensus, with some consideration for dose-related toxicity in pediatric patients. The glucocorticoid use consensus was largely consistent with adult AAV guidelines, including the use of intravenous methylprednisolone at induction onset followed by daily oral prednisone.
To accurately compare all these treatment plans, researchers defined disease inactivity or significant improvement as primary outcome measures of the remission-induction treatments, and disease inactivity, time to first relapse, or absence of relapse after two years as primary goals of the remission-maintenance treatments.
Secondary outcome measures of damage, morbidity, and quality of life were also determined.
After the plans were established, researchers randomly selected 100 CARRA members to assess their agreement with those plans.
Among the 80 who provided valid responses, 94% approved the remission-induction plan and 98% agreed with the remission-maintenance plan. A total of 96% also approved the proposed outcome measures, 91% and 92% approved the proposed prednisone and intravenous methylprednisolone regimens, and 98% agreed in principle to participate in a registry-based comparative assessment of consensus-based treatments.
“CARRA endorsement aimed to engage more members to participate in a registry-based evaluation of [pediatric] AAV and allow systematic evaluation of limited treatment alternatives,” the researchers wrote. “Increasing utilization of the registry internationally would facilitate the evaluation of other emerging therapies or strategies.”