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Cyclophosphamide ‘Not Dead Yet’ for ANCA-associated Vasculitis
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SAN DIEGO — Although fading from use in vasculitis management strategies, cyclophosphamide still offers several benefits for a minority of patients who are unable to switch to other therapies, according to a presenter at the 2019 Congress of Clinical Rheumatology West.
“Cyclophosphamide is not dead yet,” Philip Seo, MD, MHS, director of the Johns Hopkins Vasculitis Center, told attendees. “It is clearly dying as treatment for ANCA-associated vasculitis but I actually do prescribe it on a semi-regular basis.”
Seo noted that cyclophosphamide exhibits several advantages over other vasculitis treatments, such as rituximab (Rituxan, Genentech), namely the speed at which the therapy takes effect.
“With cyclophosphamide, I start to see patients move in a couple of weeks — with rituximab, it takes about a month,” he said. “For the majority of patients, I can float them for those extra couple weeks with a high dose of steroids. For most patients, it doesn’t matter, but for some patients it does and, in those patients, I would opt for cyclophosphamide.”
In addition, having the option of cyclophosphamide is key when delayed approval and scheduling for a rituximab infusion prevent treatment for a patient in need.
“Quite simply, cyclophosphamide sometimes works faster because you cannot get approval for rituximab,” Seo said. “Even for me, it takes 2 to 3 weeks minimum to get approval for an infusion center to give a dose of rituximab. Again, for some patients, I can float them, but some patients cannot wait to get started so I would probably start them on cyclophosphamide if I had the option.”
Recognizing that many younger clinicians may be unfamiliar with cyclophosphamide, Seo offered some “tips and tricks” for administering this medication. Most importantly, he noted that the standard dosage of cyclophosphamide is 2 mg/kg daily for 3 months.
“Of course, there are some exceptions to the rule,” he said. “If you have a patient with Behcet’s disease — not the person who has an occasional oral ulceration, but someone from Saudi Arabia who has neuro-Behcet’s with multiple organ involvement — that patient should receive 2.5 mg/kg.”
On the other hand, he recommended that older patients or patients with renal insufficiency should be administered less — 1 to 1.5 mg/kg daily — and adjust the dose according to what patients can tolerate.
“If you look at the literature, it claims that cyclophosphamide is not dependent on renal clearance, but if you don’t adjust the dose, you will kill patients,” Seo said. “You have to start lower and see how they do, and maybe only bump it up once they are tolerating the dose.”
Lastly, he highlighted the importance of monitoring the duration of cyclophosphamide in patients. According to Seo, if after 3 months of therapy, the patient has sufficiently responded, they can be transitioned to a remission maintenance strategy.
“However, at 3 months, if you are not sure — if you had to slow down the prednisone taper or the acute phase reactions are higher than you think they should be — then go ahead and opt for the extra 3 months,” Seo said. “Honestly, the toxicity associated with an additional 3 months of cyclophosphamide is nothing compared with the toxicity associated with the extra doses of prednisone you would give that patient if you are not completely treating their inflammation.”– by Robert Stott
Reference:
Seo P. ANCA-associated vasculitis. Presented at: Congress of Clinical Rheumatology West; September 26-29, 2019; San Diego.
Disclosure: Seo reports no relevant financial disclosures.