Team: RAVE Trial, aka “Team PR3 (Perpetually Raining 3’s)”

Region: Jump ball

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. PMID: 20647199.

Authors: Wake Forest Rheumatology Fellowship Program. Khiem Vu, MD, Second-Year Rheumatology Fellow, Rachel Wolfe, MD, Assistant Professor, Jon Golenbiewski, DO, Assistant Professor.

Team Overview

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

A major shift occurred after the publication of the 2010 Rituximab (RTX) in ANCA-Associated Vasculitis (RAVE) trial in the NEJM by Stone et al. A multicenter, randomized, double-blind, double-dummy, non-inferiority trial, it compared RTX with steroids to oral CYC with steroids for remission induction in 197 patients with newly diagnosed and relapsing AAV over 6 months. The results of this study have changed the standard of care ever since; the RTX-based regimen was found to be noninferior to CYC in achieving steroid-free, complete disease remission at 6-month follow up. Additionally, RTX was superior to CYC in achieving remission for relapsing cases of AAV at baseline. Moreover, there was no significant increase in adverse effects in RTX compared to CYC treatment arm.

Impact on Rheumatology

The 2010 RAVE trial is one of the most important developments in modern rheumatology. The preference of RTX over CYC for severe AAV (whether new-onset or relapsing) continues to this day, as reflected in the first ever 2021 joint guideline by the American College of Rheumatology/Vasculitis Foundation for the management of AAV. The toppling of CYC from its four decades of “G.O.A.T” status underscores that accepting the status quo is incompatible in a field like rheumatology, and we should always strive for improving the care of our patients.

Chances in the Tournament

It’s quite clear that we are the team to beat! We are the only team in the tournament with RAVE reviews, what a very impressive feat! Siding with another team would be like choosing CYC over Rituximab; sure, it works and may get you the “W”, but why would you choose a team that will do nothing but trouble you? Although we are confident in our chances in the tournament, we do expect to run into some tough competition from the other non-inferiority trials. There has been lots of talk about a lupus nephritis trial that also aimed to dethrone CYC, but with a different agent, mycophenolate. However, we are only modestly impressed, at best. After all, “The enemy of my enemy is [not always] my friend”. Should you choose to go with another team, the ref will surely blow their whistle for a travel; naysayers tread lightly, as you will watch your bracket unravel.

Next scouting report: HCQ Withdrawal

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the Jump Ball region: Is there a role for monitoring serum ANCAs to assess ANCA associated vasculitis disease activity?

References

1. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021 Aug;73(8):1366-1383. doi: 10.1002/art.41773. Epub 2021 Jul 8. PMID: 34235894.
2. Cohen, Ben. “The Mentor who made Dr. Anthony Fauci”. The Wall Street Journal. April 16, 2020. https://www.wsj.com/articles/the-mentor-who-made-dr-anthony-fauci-11587040520
3. Fauci AS, Wolff SM. Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine (Baltimore). 1973;52(6):535-561.
4. Maugh, Thomas. “Researchers find new therapy for vasculitis”. Los Angeles Times. July 14, 2010. https://www.latimes.com/archives/la-xpm-2010-jul-14-la-heb-vasculitis-20100714-story.html.
5. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. PMID: 20647199