If prior tournaments are any indication, landmark clinical trials from TNF Takedown, RA Revamp, Get in the Game, and Jump Ball are likely to be layups in the tournament. However, the broad impact of this study—addressing more than a single disease—is the reason it is likely to be a slam dunk over these trials, none of which have been cited as many times (i.e., have as many wins) as the paper by Arbuckle et al.

All authors are part of the Rheumatology Fellowship Program at Massachusetts General Hospital, Boston.

Reference

1. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526–1533.

Disclosures

Marcy B. Bolster, MD, has received grants from the Rheumatology Research Foundation and is a member of the ACR Board of Directors.

Team PR3

Rituximab supplants cyclophosphamide in AAV treatment

BY KHIEM VU, MD, RACHEL WOLFE, MD, & JON GOLENBIEWSKI, DO

Base Article

Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–232.¹

Team Overview

For many years, the combination of cyclophosphamide and high-dose glucocorticoids was standard of care for remission induction in ANCA-associated vasculitis (AAV). Introduced in the early 1970s by then 32-year-old Anthony Fauci, MD, and his mentor, Sheldon Wolff, PhD, this cyclophosphamide-based regimen transformed what used to be a near-death sentence into a manageable, chronic disease.^2-5 Nevertheless, cyclophosphamide is associated with significant infectious risk as well as other potential life-changing side effects, including infertility, hemorrhagic cystitis and secondary malignancies. Better treatment options were needed.

A major shift occurred after the publication of the 2010 Rituximab in ANCA-Associated Vasculitis (RAVE) trial in The New England Journal of Medicine by Stone et al.¹ A multi-center, randomized, double-blind, double-dummy, non-inferiority trial, it compared rituximab with glucocorticoids to oral cyclophosphamide with glucocorticoids for remission induction in 197 patients with newly diagnosed and relapsing AAV over six months.

The results of this study have changed the standard of care ever since; the rituximab-based regimen was found to be noninferior to cyclophosphamide in achieving glucocorticoid-free, complete disease remission at six-month follow-up. Additionally, rituximab was superior to cyclophosphamide in achieving remission for relapsing cases of AAV at baseline. Moreover, there was no significant increase in adverse effects with rituximab compared with cyclophosphamide.

Impact on Rheumatology

The 2010 RAVE trial is one of the most important developments in modern rheumatology. The preference of rituximab over cyclophosphamide for severe AAV (whether new-onset or relapsing) continues to this day, as reflected in the first ever 2021 joint guideline by the ACR/Vasculitis Foundation for the management of AAV. The toppling of cyclophosphamide from its four decades of GOAT status (i.e., greatest of all time) underscores that accepting the status quo is incompatible in a field like rheumatology, and we should always strive to improve the care of our patients.