Team: CYC in polyarteritis nodosa (PAN), aka “Fauci’s Power Forward”
Region: Get in the Game
Base article: Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979 Aug 2;301(5):235-8. doi: 10.1056/NEJM197908023010503. PMID: 36563.
Authors: Allegheny Health Network Rheumatology Fellowship. Zaina Shahid, MD, first year rheumatology fellow, Nicholas Wiemer, DO, second year rheumatology fellow, Sara Shahid, MD, first year rheumatology fellow, Michael Lucke, MD, Rheumatology Program Director,
Before 1970, the prognosis of systemic necrotizing vasculitis was abysmal, almost uniformly fatal. Dr. Walton in his survey of 56 patients with systemic vasculitis found the average survival time to be 5 months with 81% of the patients dead within one year of diagnosis.1 The 5-year survival rate of a cohort of patients from 1946-1962 with a diagnosis termed periarteritis nodosa, the prototypical systemic necrotizing vasculitis, was only 15% in untreated patients. Corticosteroids were the mainstay of treatment improving survival rate to only 48% .2
It was in this grim setting that Drs. Anthony Fauci and Sheldon Wolff reported on 17 patients with severe necrotizing vasculitis studied over the course of 11 years.3 16 of these patients had been treated with corticosteroids for a mean duration of 22 months and had suffered from severe side effects. All 16 patients showed subjective and objective evidence of disease progression despite treatment with corticosteroids. 16 patients were treated with cyclophosphamide 2mg/kg oral per day. 1 patient chose to continue azathioprine. A taper of corticosteroids was initiated within 2 weeks of receiving cyclophosphamide with the goal of discontinuation. 14 patients showed definite remission within 3 weeks of cyclophosphamide therapy. The mean duration of cyclophosphamide induced remission was 22 months with notably no relapses while being on cyclophosphamide. At the end of the study period, remission was achieved in all 17 patients in the study!
Impact on Rheumatology
This dramatic response to cyclophosphamide represented the first important advancement in the management of necrotizing vasculitis. This momentous discovery had significant impact on the lives of patients with systemic vasculitis. Before this break-through, the average survival time after diagnosis was 5 months. Now, because of the use of cyclophosphamide and the work done by Drs. Fauci and Wolff, this previously devastating disease has an effective treatment improving the survival rate to almost 80% at 5 years.4 It was a joyous moment for rheumatologists and patients alike. Cyclophosphamide remained the MVP for many years to come as standard induction treatment of vasculitis. This legendary player went on to compete against other legends of the game, including rituximab. However, rituximab has never been able to surpass cyclophosphamide as an offensive player. Additionally, cyclophosphamide set the stage for innovative treatment in numerous other rheumatic conditions ranging from pulmonary disease in scleroderma, lupus nephritis, and refractory cutaneous and myositis diagnoses. It also remains a treatment of choice for remission induction in some forms of severe vasculitis .5 This landmark trial continues to impact the field of Rheumatology 50 years since publication.
Chances in the Tournament
A breakout, offensive star like cyclophosphamide is sure to be game changer for this tournament. A player of this skill hasn’t been seen since Cortisone played back in 1949 for Mayo. Combined with the skill of Dr. Fauci, a fan favorite known for sinking shots while under immense pressure from the most imposing defenses, this team will be an overwhelming force in the games to come.
Next scouting report: CYC in Scleroderma
Back to the full list of scouting reports.
See the Q&A on theMednet.org for the Get in the Game region: Are there patients in whom you would avoid initiating of ULT during acute gout flare?
- Hollander D, Manning RT. The use of alkylating agents in the treatment of Wegener’s granulomatosis. Ann Intern Med. 1967 Aug;67(2):393-8. doi: 10.7326/0003-4819-67-2-393. PMID: 6036397.
- Frohnert PP, Sheps SG. Long-term follow-up study of periarteritis nodosa. Am J Med. 1967 Jul;43(1):8-14. doi: 10.1016/0002-9343(67)90144-1. PMID: 4157287.
- Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979 Aug 2;301(5):235-8. doi: 10.1056/NEJM197908023010503. PMID: 36563.
- Catherine King, Lorraine Harper, Mark Little, The complications of vasculitis and its treatment, Best Practice & Research Clinical Rheumatology, Volume 32, Issue 1,2018,Pages 125-136,ISSN 1521-6942 https://doi.org/10.1016/j.berh.2018.07.009.
- 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 Rheumatology. 2021 Aug;73(8):1366-1383. doi: 10.1002/art.41773. Epub 2021 Jul 8. PMID: 34235894.